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1.	Einarsdottir, Ingibjörg, 1951, et al. (author) Atlantic halibut growth hormone: structure and plasma levels of sexually mature males and females during photoperiod-regulated annual cycles 2002 In: General and Comparative Endocrinology. - 0016-6480 .- 1095-6840. ; 127:1, s. 94-104 Journal article (peer-reviewed)abstract The main objectives of this study were to obtain the amino acid sequence of Atlantic halibut (Hippoglossus hippoglossus) growth hormone (hhGH) and compare it with other teleost species, to establish a radioimmunoassay to assess plasma hhGH levels and thus to gain information about possible biological functions and regulation by photoperiod. The hhGH gene was cloned and its amino acid sequence deduced from the cDNA. The mature hhGH protein consists of 186 amino acids. Comparison with other flatfish species as well as a species from a different order, the pufferfish, reveals that the sequence similarities of the mature hhGH with that of the barfin flounder, the Japanese flounder, the sole and the pufferfish are 99.5, 81.7, 74.2, and 65.2%, respectively. The sequence similarities appear to correctly reflect the gross phylogenetic relationships among these telcost species. A specific GH-RIA was developed for measurements of Atlantic halibut GH levels. Assessment of plasma GH levels in adult halibut revealed large gender differences, with GH levels frequently being an order of magnitude higher in males than females. The mean (+/-SEM) plasma GH for males kept on normal annual photoperiod were 25.2 +/- 6.11 ng ml(-1) and for females were 5.14 +/- 1.94 ng ml(-1). It appears likely that plasma growth hormone levels in Atlantic halibut can be inversely correlated to growth and metabolism. Shifting of the annual photoperiod cycles demonstrated that photoperiod in not a regulator of plasma GH levels in the Atlantic halibut. but further research is needed to assess whether GH plays a role in the reproduction of this marine teleost species. (C) 2002 Elsevier Science (USA). All rights reserved.
2.	von Hofsten, Jonas, et al. (author) Fushi tarazu factor-1 mRNA and protein is expressed in steroidogenic and cholesterol metabolising tissues during different life stages in Arctic char (Salvelinus alpinus) 2003 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 132:1, s. 96-102 Journal article (peer-reviewed)abstract Fushi tarazu factor-1 (FTZ-F1) genes belong to the nuclear receptor family 5A (NR5A). The distribution pattern of NR5A genes in teleosts suggests that they control functions separate to, or in addition to, those of other vertebrates. In mammals NR5A1 genes, including steroidogenic factor-1 (SF-1), are primarily involved in steroidogenesis. NR5A2 contain the alpha-fetoprotein transcription factor (FTF) genes, which protect mammalian embryos against maternal estrogens, and are involved in cholesterol transfer and metabolism. In this study we have analysed the expression of two Arctic char FTZ-F1 forms belonging to the NR5A2 group. The expression starts during early development and the transcripts are present in embryonic liver/pancreas and gonadal regions. The genes are up-regulated during embryogenesis as the embryo develops towards hatch, as shown by increased mRNA and protein levels. In adult Arctic char the FTZ-F1 forms are primarily located to tissues involved in steroidogenesis as well as cholesterol metabolism. Thus, a division of NR5A into SF-1 (NR5A1) and FTF (NR5A2) specific functions does not appear to have occurred in teleosts.
3.	von Hofsten, Jonas, et al. (author) Fushi tarazu factor-1 mRNA and protein is expressed in steroidogenic and cholesterol metabolising tissues during different life stages in Arctic char (Salvelinus alpinus) 2003 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 132:1, s. 96-102 Journal article (peer-reviewed)abstract Fushi tarazu factor-1 (FTZ-F1) genes belong to the nuclear receptor family 5A (NR5A). The distribution pattern of NR5A genes in teleosts suggests that they control functions separate to, or in addition to, those of other vertebrates. In mammals NR5A1 genes, including steroidogenic factor-1 (SF-1), are primarily involved in steroidogenesis. NR5A2 contain the alpha-fetoprotein transcription factor (FTF) genes, which protect mammalian embryos against maternal estrogens, and are involved in cholesterol transfer and metabolism. In this study we have analysed the expression of two Arctic char FTZ-F1 forms belonging to the NR5A2 group. The expression starts during early development and the transcripts are present in embryonic liver/pancreas and gonadal regions. The genes are up-regulated during embryogenesis as the embryo develops towards hatch, as shown by increased mRNA and protein levels. In adult Arctic char the FTZ-F1 forms are primarily located to tissues involved in steroidogenesis as well as cholesterol metabolism. Thus, a division of NR5A into SF-1 (NR5A1) and FTF (NR5A2) specific functions does not appear to have occurred in teleosts.
4.	Berg, A. H., et al. (author) Regulation of Arctic char (Salvelinus alpinus) egg shell proteins and vitellogenin during reproduction and in response to 17β-estradiol and cortisol 2004 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 135:3, s. 276-285 Journal article (peer-reviewed)abstract Estrogens induce both vitellogenin (Vtg) and egg shell (zona pellucida; ZP) protein synthesis in salmonids. However, while Vtg is strictly under estrogenic control, recent reports suggest that additional mechanisms are involved in ZP protein synthesis. During sexual maturation both estrogen and glucocorticoid levels increase in the circulation of female fish. As glucocorticoids have been shown to interfere with Vtg induction in fish we investigated whether cortisol (F) had similar effects on ZP regulation. In the present study we determined both the natural variation in Vtg and ZP during an annual reproductive cycle in female Arctic char (Salvelinus alpinus), and the effect of co-treatment of juvenile Arctic char with 17β-estradiol (E2) and F. During sexual maturation the expression of Vtg and ZP correlated to plasma levels of E2 and F. Determination of Vtg and ZP protein levels following co-treatment with E2 and F showed that F antagonized E2 induction of Vtg. However, F was observed to potentiate the expression of ZP protein in the same fish. These results indicate that in Arctic char Vtg and ZP proteins are not regulated by the same mechanisms and suggest that ZP protein expression does not necessarily imply exposure to estrogenic compounds alone, and may thus not be ideally suited as a biomarker of exposure to estrogenic compounds.
5.	Blixt, Martin, 1977-, et al. (author) Characterization of β-cell function of pancreatic islets isolated from bank voles developing glucose intolerance/diabetes : an animal model showing features of both type 1 and type 2 diabetes mellitus, and a possible role of the Ljungan virus 2007 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 154:1-3, s. 41-47 Journal article (peer-reviewed)abstract Bank voles (Clethrionomys glareolus) kept in captivity develop diabetes mellitus to a significant extent. Also in wild bank voles, elevated blood glucose has been observed. A newly isolated picornavirus named Ljungan virus (LV) has been found in the pancreas of these bank voles. Moreover, LV infection in combination with environmental factors may cause glucose intolerance/diabetes (GINT/D) in normal mice. The aim of the present study was to investigate the functional characteristics of pancreatic islets, isolated from bank voles, bred in the laboratory but considered LV infected. About 20% of all males and females were classified as GINT/D following a glucose tolerance test. Of these animals the majority had become diabetic by 20 weeks of age, with a tendency towards an earlier onset in the males. GINT/D animals had increased serum insulin levels. Islets were tested on the day of isolation (day 0) and after 1 week of culture for their insulin content and their capacity to synthesize (pro)insulin, secrete insulin and metabolize glucose. Functional differences could be observed between normal and GINT/D animals as well as between genders. An elevated basal insulin secretion was observed on day 0 indicating β-cell dysfunction among islets isolated from diabetic males. In vitro culture could reverse some functional changes. The increased serum insulin level and the increased basal islet insulin secretion may suggest that the animals had developed a type 2 diabetes-like condition. It is likely that the putative stress imposed in the laboratory, maybe in combination with LV infection, can lead to an increased functional demand on the β-cells.
6.	Brunström, Björn, et al. (author) Effects of estrogens on sex differentiation in Japanese quail and chicken 2009 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 163:1-2, s. 97-103 Journal article (peer-reviewed)abstract Estrogen production by the female avian embryo induces development of a female phenotype of the reproductive organs whereas the low estrogen concentration in the male embryo results in a male phenotype. Treatment of female embryos with exogenous estrogens disrupts Müllerian duct development resulting in malformations and impaired oviductal function. Exposure of male embryos to estrogens results in ovotestis formation and persisting Müllerian ducts in the embryos and testicular malformations, reduced semen production and partially developed oviducts in the adult bird. Furthermore, studies in Japanese quail show that the male copulatory behavior is impaired by embryonic estrogen treatment. Results from our experiments with selective agonists for ERalpha and ERbeta suggest that the effects of estrogens on the reproductive organs are mediated via activation of ERalpha. Abundant expression of ERalpha mRNA was shown in gonads and Müllerian ducts of early Japanese quail embryos. Both ERalpha and ERbeta transcripts were detected by real-time PCR in early embryo brains of Japanese quail indicating that both receptors may be involved in sex differentiation of the brain. However, in 9-day-old quail embryo brains in situ hybridization showed expression of ERbeta mRNA, but not of ERalpha mRNA, in the medial preoptic nucleus (POM) and the bed nucleus of the stria terminalis (BSTm), areas implicated in copulatory behavior of adult male quail. Furthermore, embryonic treatment with the selective ERalpha agonist propyl pyrazol triol (PPT) had no effect on the male copulatory behavior. These results suggest that ERbeta may be important for the effects of estrogens on brain differentiation.
7.	Cardoso, Joao C. R., et al. (author) Comparative evolution of peptide hormone-binding GPCRs : A route to understanding functional complexity 2014 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 209:SI, s. 1-2 Journal article (other academic/artistic)
8.	Cardoso, João C R, et al. (author) New insights into the evolution of vertebrate CRH (corticotropin-releasing hormone) and invertebrate DH44 (diuretic hormone 44) receptors in metazoans 2014 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 209:SI, s. 162-170 Journal article (peer-reviewed)abstract The corticotropin releasing hormone receptors (CRHR) and the arthropod diuretic hormone 44 receptors (DH44R) are structurally and functionally related members of the G protein-coupled receptors (GPCR) of the secretin-like receptor superfamily. We show here that they derive from a bilaterian predecessor. In protostomes, the receptor became DH44R that has been identified and functionally characterised in several arthropods but the gene seems to be absent from nematode genomes. Duplicate DH44R genes (DH44 R1 and DH44R2) have been described in some arthropods resulting from lineage-specific duplications. Recently, CRHR-DH44R-like receptors have been identified in the genomes of some lophotrochozoans (molluscs, which have a lineage-specific gene duplication, and annelids) as well as representatives of early diverging deuterostomes. Vertebrates have previously been reported to have two CRHR receptors that were named CRHR1 and CRHR2. To resolve their origin we have analysed recently assembled genomes from representatives of early vertebrate divergencies including elephant shark, spotted gar and coelacanth. We show here by analysis of synteny conservation that the two CRHR genes arose from a common ancestral gene in the early vertebrate tetraploidizations (2R) approximately 500 million years ago. Subsequently, the teleost-specific tetraploidization (3R) resulted in a duplicate of CRHR1 that has been lost in some teleost lineages. These results help distinguish orthology and paralogy relationships and will allow studies of functional conservation and changes during evolution of the individual members of the receptor family and their multiple native peptide agonists.
9.	Elofsson, Ulf, et al. (author) Intermale competition in sexually mature arctic charr : effects on brain monoamines, endocrine stress responses, sex hormone levels, and behavior. 2000 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 118:3, s. 450-60 Journal article (peer-reviewed)abstract Sexually mature Arctic charr (Salvelinus alpinus) males were allowed to interact in pairs for 4 days in the absence of females. Agonistic behavior was quantified, and at the end of the experiment, plasma levels of glucose, cortisol, testosterone (T), 11-ketotestosterone (11-KT), and 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha, 20beta-P) were determined alongside brain concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA, the major 5-HT metabolite), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC, a major DA metabolite). Plasma cortisol and glucose were significantly elevated in subordinate fish, and the number of aggressive acts received showed positive correlations with plasma levels of glucose on day 1, during the development of the dominance relationship, and of cortisol on day 4, when the dominance relationship was established. In contrast, plasma concentrations of T and 11-KT were significantly higher in dominant than in subordinate males, and there was a similar tendency in plasma concentrations of 17alpha,20beta-P. Further, plasma levels of these gonadal steroids were correlated with the number of aggressive acts performed on day 4, but not with the number of aggressive acts received. The plasma cortisol concentrations did not correlate with either 5-HIAA:5-HT or DOPAC:DA ratios in any of the brain parts analyzed. Plasma glucose levels showed positive correlations with brain 5-HIAA:5-HT ratios. Negative correlations were observed between 5-HIAA:5-HT ratios in the optic tectum and between plasma levels of T, 11-KT, and 17alpha,20beta-P. Telencephalic DOPAC/DA ratios displayed a negative correlation with plasma levels of T, 11-KT, and 17alpha,20beta-P, but only in dominant males.
10.	Fahlman, Åsa (author) Cortisol and corticosterone independence in cortisol-dominant wildlife 2012 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 177, s. 113-119 Journal article (peer-reviewed)abstract Species have traditionally been defined as cortisol-dominant or corticosterone-dominant, depending on the glucocorticoid that is reported. To assess the degree of covariance versus independence between cortisol and corticosterone, 245 serum samples belonging to 219 individuals from 18 cortisol-dominant, non-domesticated species (6 mammalian orders) were compared by mass spectrometry. In these samples, which were elevated above baseline, concentration ranges were overlapping for cortisol and corticosterone although cortisol was dominant in every sample except one of 17 bighorn sheep with a corticosterone-biased cortisol-to-corticosterone ratio of 0.17. As expected, cortisol and corticosterone were strongly associated among species (r(2) = 0.8; species with high absolute cortisol tend to have high absolute corticosterone concentrations), with wide variation in the species-average cortisol-to-corticosterone ratio (range 7.5-49) and an even wider ratio range across individuals (0.2-341). However, only 9 out of 13 species with >7 individuals showed a positive association between cortisol and corticosterone among individuals, and repeated measures of the cortisol-to-corticosterone ratio within individuals were weakly associated (CV range 3-136%). We conclude that corticosterone, although at lower concentrations, has the potential to signal independently of cortisol, and should be included in integrated endocrine models of stress responses. (C) 2012 Elsevier Inc. All rights reserved.
11.	Gong, Ningping, 1979, et al. (author) Impaired central leptin signaling and sensitivity in rainbow trout with high muscle adiposity 2016 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 235, s. 48-56 Journal article (peer-reviewed)abstract The hormone leptin has been identified in all vertebrate classes, but its physiological roles in non-mammalian vertebrates are not well defined. To elucidate leptin regulation in energy homeostasis in a teleost fish species, this study compares hypothalamic and pituitary leptin signaling systems in energetically divergent rainbow trout lines selected for low (lean line, LL) and high (fat line, FL) muscle adiposity under feeding and starvation conditions. In fed fish, hypothalamic gene expression and protein density of the full-functional leptin receptor (LepRL), as well as a leptin binding protein (LepBP) expression, are lower in FL than LL fish. The FL fish have also lower activation of leptin-relevant signaling pathways involving protein kinase B (Akt) and extracellular signal-related kinase. These observations suggests impaired central leptin action in FL fish. During fasting, hypothalamic LepRL and LepBP expression, as well as active Akt levels are downregulated after one week, while pituitary LepRL expression is upregulated, in the LL fish only. After four weeks, hypothalamic LepRL protein levels return to normal levels in both fish lines and Akt is reactivated, although not to the same extent in FL as in LL fish, indicating that FL fish have low leptin sensitivity to nutritional changes. Neuropeptide Y and orexin expression is downregulated to similar levels in both fish lines after one-week fasting. The divergent leptin system profiles between the two fish lines demonstrate that phenotypic selection for high muscle adiposity affects leptin endocrinology, indicating regulatory roles for leptin in rainbow trout energy homeostasis. © 2016 Elsevier Inc.
12.	Hallgren, Stefan, 1978-, et al. (author) Inhibition of cytochrome p450 brain aromatase reduces two male specific sexual behaviours in the male Endler guppy (Poecilia reticulata) 2006 In: General and Comparative Endocrinology. - Amsterdam, The Netherlands : Elsevier. - 0016-6480 .- 1095-6840. ; 147:3, s. 323-328 Journal article (peer-reviewed)abstract In mammalian and avian vertebrate groups, androgens act as controlling agents on male aggression and courtship behaviour by their conversion to oestrogens by cytochrome P450 aromatase in well-defined brain regions. Despite the fact that bony fishes have exceptionally high brain aromatase activity, little is known about it’s possible regulatory effects on the reproductive behaviours of teleosts. In this study, Endler guppy males (Poecilia reticulata) were subjected to 26–29 days of 24-h exposure to two different concentrations (15 and 100 μg/L) of the aromatase inhibitor fadrozole in the water. Compared with the control males, two of three courtship activities in males exposed to the higher concentration were reduced when they were paired with receptive stimulus females. Reduction in brain aromatase activity was confirmed in both exposed groups with the use of the tritiated water assay.
13.	Heimeier, RA, et al. (author) Amphibian metamorphosis as a model for studying endocrine disruption on vertebrate development: effect of bisphenol A on thyroid hormone action 2010 In: General and comparative endocrinology. - : Elsevier BV. - 1095-6840 .- 0016-6480. ; 168:2, s. 181-189 Journal article (peer-reviewed)
14.	Henriksen, Rie, et al. (author) Maternal corticosterone elevation during egg formation in chickens (Gallus gallus domesticus) influences offspring traits, partly via prenatal undernutrition 2013 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 191, s. 83-91 Journal article (peer-reviewed)abstract The relationship between maternal stress during pregnancy in humans and the subsequent physical and mental health disorders in their children has inspired a wide array of studies on animal models. Almost all of these studies have used mammalian species, but more recently oviparous species in which the embryo develops outside the mothers body have received more attention. These new models facilitate disentangling of the underlying mechanism due to the accessibility of the prenatal environment, the egg. Studies in birds have found that maternal stress during egg formation induces phenotypic alterations in the offspring that hatch from these eggs. However, different offspring traits have been measured in different studies and potential underlying mechanisms are barely addressed. In this study we experimentally manipulated maternal corticosterone levels in laying hens. We found that mothers with experimentally elevated plasma corticosterone levels produced offspring that are smaller at hatching, less competitive, less fearful, have lower immunocompetence and higher plasma testosterone levels, as well as an alteration of visually guided behavioural lateralization. Earlier we have showed that eggs produced by these corticosterone treated mothers were lighter and contained lower concentrations of testosterone and progesterone in the yolk. While yolk hormones showed no correlation with any offspring traits, egg mass correlated positively with offsprings body mass from hatching until 10 days of age and hatching mass correlated positively with the offsprings ability to compete for food, indicating that prenatal under nutrition might mediate some effects of maternal stress.
15.	Ingberg, Edvin, 1988-, et al. (author) Methods for long-term 17β-estradiol administration to mice 2012 In: General and Comparative Endocrinology. - Maryland Heigths, USA : Elsevier. - 0016-6480 .- 1095-6840. ; 175:1, s. 188-193 Journal article (peer-reviewed)abstract Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets.
16.	Jansson, Erika, et al. (author) Sex-dependent expression of anti-Müllerian hormone (amh) and amh receptor 2 during sex organ differentiation and characterization of the Müllerian duct development in Xenopus tropicalis 2016 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 229, s. 132-144 Journal article (peer-reviewed)abstract Amphibian gonadal differentiation involves the action of sex steroids. Recent research indicates that the anti-Müllerian hormone (AMH) is involved in testicular development in some lower vertebrate species. For amphibians there is a lack of data on ontogenetic expression of the AMH receptor AMHR2/amhr2 and of progesterone receptors (PGRS/pgrs). Here we expand the knowledge on amphibian sex differentiation by characterizing ontogenetic mRNA levels of amh, amhr2, intracellular and membrane pgrs (ipgr and mpgr beta) and cytochrome P450 19a1 (cyp19a1) (ovarian marker) in the urogenital complex of the model species Xenopus (Silurana) tropicalis. Furthermore, we characterized the ontogenetic development of the Müllerian ducts (precursors of the female reproductive tract) histologically. The developmental period investigated spanned from beginning of gonadal differentiation, Nieuwkoop and Faber (NF) stage 51, to 4weeks post-metamorphosis. The Müllerian ducts were first observed at NF 64 in both sexes. Male-enhanced amh mRNA levels from NF 53/54 to 6days post-metamorphosis and female-enhanced cyp19a1 levels from NF 53 to 4weeks post-metamorphosis were noted. The sexually dimorphic mRNA level profile was more distinct for amh than for cyp19a1. The pgrs mRNA levels increased over the studied period and showed no sex differences. At later developmental stages, the amhr2 mRNA level was increased in putative females compared with males. Our findings suggest that AMH has a role in gonadal differentiation in X. tropicalis. We propose relative gonadal amh mRNA level as a testicular marker during early gonadal development in amphibians.
17.	Kalliokoski, Otto, et al. (author) Distribution and time course of corticosterone excretion in faeces and urine of female mice with varying systemic concentrations 2010 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 168:3, s. 450-454 Journal article (peer-reviewed)abstract Quantification of corticosterone metabolites excreted in faeces and urine is increasingly being used for assessment of preceding corticosterone concentrations in the circulation. This is a promising approach to non-invasive stress assessment in laboratory rodents. It is however unknown whether the proportions of corticosterone metabolites excreted in faeces and urine may differ, depending on the concentration of corticosterone in blood. This uncertainty undermines the applicability of urinary and faecal corticosterone metabolite measurements as biomarkers for stress. Therefore, the terminal distribution and time course of corticosterone excretion, after intravenous injection of varying corticosterone concentrations, was investigated in female mice. Female BALB/c mice excreted 60% of all corticosterone in the urine with an approximate delay of 5 h from tail vein administration. The remaining 40% were excreted in faeces, with an approximate delay of 9 h from administration. The faecal/urinary excretion ratio, as well as time course of excretion, remained unaltered by administration of various doses of corticosterone covering the entire physiological range of serum corticosterone. Although currently untested for other strains of mice and species of animals, these findings add credence to the utility of faecal and urinary corticosterone as non-invasive biomarkers for physiological stress.
18.	Karlsson, Anna-Carin, et al. (author) A domestication related mutation in the thyroid stimulating hormone receptor gene (TSHR) modulates photoperiodic response and reproduction in chickens 2016 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 228, s. 69-78 Journal article (peer-reviewed)abstract The thyroid stimulating hormone receptor gene (TSHR) has been suggested to be a "domestication locus" in the chicken. A strong selective sweep over TSHR in domestic breeds together with significant effects of a mutation in the gene on several domestication related traits, indicate that the gene has been important for chicken domestication. TSHR plays a key role in the signal transduction of seasonal reproduction, which is characteristically less strict in domestic animals. We used birds from an advanced intercross line between ancestral Red Junglefowl (RJF) and domesticated White Leghorn (WL) to investigate effects of the mutation on reproductive traits as well as on TSHB, TSHR, DIO2 and DIO3 gene expression during altered day length (photoperiod). We bred chickens homozygous for either the mutation (d/d) or wild type allele (w/w), allowing assessment of the effect of genotype at this locus while also controlling for background variation in the rest of the genome. TSHR gene expression in brain was significantly lower in both did females and males and did females showed a faster onset of egg laying at sexual maturity than wow. Furthermore, did males showed a reduced testicular size response to decreased day length, and lower levels of TSHB and DIO3 expression. Additionally, purebred White Leghorn females kept under natural short day length in Sweden during December had active ovaries and lower levels of TSHR and DIO3 expression compared to Red Junglefowl females kept under similar conditions. Our study indicates that the TSHR mutation affects photoperiodic response in chicken by reducing dependence of seasonal reproduction, a typical domestication feature, and may therefore have been important for chicken domestication.
19.	Kobayashi, Yuki, et al. (author) Differential expressions of melanocortin receptor subtypes in melanophores and xanthophores of barfin flounder 2010 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 168:1, s. 133-142 Journal article (peer-reviewed)abstract alpha-Melanocyte-stimulating hormone (alpha-MSH) is a member of the melanocortin (MC) family, and the MC receptor (MCR) is a member of the G protein-coupled receptor (GPCR) superfamily. We previously found that in barfin flounder, a flatfish, alpha-MSH with an acetyl group at the N-terminus stimulated pigment dispersion in xanthophores; however, this effect was not observed in melanophores. Therefore, the present study was undertaken to find which MCR subtypes are expressed in these pigment cells in order to elucidate how acetylation regulates activities of alpha-MSH-related peptides. Here, we also report the cloning of Mc1r and Mc5r from barfin flounder. Three types of cells-melanophores, xanthophores, and nonchromatophoric dermal cells-were isolated from the skin samples collected from the dorsal fin. These cells were then tested for the expression of Mc1r and Mc5r as well as Mc2r and Mc4r that we had previously cloned. Mc1r and Mc5r transcripts were detected in melanophores, and a sole Mc5r transcript was detected in xanthophores. We had previously found that the efficiency of alpha-MSH was higher than that of desacetyl-alpha-MSH for pigment dispersion in xanthophores. Acetylated MSH peptide may have increased binding affinity to MC5R, whereas alpha-MSH lacks melanin-dispersing activity. Increasing evidences indicate that many GPCRs form heterodimers, and this may affect the affinity of the ligand for the corresponding GPCR. Taken together, the expression of two different Mcr subtypes in melanophores may suggest that a heterodimer consisting of MC1R and MC5R may have a low binding affinity toward alpha-MSH. The present results clarify the types of MCRs that are expressed in melanophores and xanthophores of barfin flounder; furthermore, the results provide important clues about the functional regulation of alpha-MSH-related peptides.
20.	Kobayashi, Yuki, et al. (author) Food deprivation increases the expression of melanocortin-4 receptor in the liver of barfin flounder, Verasper moseri 2008 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 155:2, s. 280-287 Journal article (peer-reviewed)abstract The melanocortin (MC) system is composed of melanocyte-stimulating hormone, adrenocorticotropic hormone and their receptors. The MC system has a role in both pigmentation and the regulation of energy homeostasis, in which MC4R, one of the five MC receptors, has a key role. Interestingly, the barfin flounder (Pleuronectiformes) reared with a black background shows retarded growth compared to white background-reared fish, which could be associated with the MC system because of its dual role in regulating pigmentation and energy status. Here, we cloned MC4R and assessed the effects of feeding status on its expression in barfin flounder. Barfin flounder MC4R. was composed of 325 amino acids and showed the highest sequence identity to MC4R of fugu (85%), followed by rainbow trout (82%), zebrafish (79%), goldfish (78%), dogfish (71%), chickens (67%), humans (67%) and mice (65%). Among 18 different tissues examined, the predominant expression of MC4R was observed in the brain, liver, testis and ovary as detected with reverse transcription PCR. Food deprivation resulted in a 4-fold increase in the number of MC4R transcripts in the liver, whereas no change was observed in the brain between fasted fish and fed controls. These results suggest that the NIC system including MC4R is associated with energy homeostasis in barfin flounder and that peripheral tissues could play a role in this regulation.
21.	Kobayashi, Yuki, et al. (author) Melanocortin receptor subtypes in interrenal cells and corticotropic activity of α-melanocyte-stimulating hormones in barfin flounder, Verasper moseri 2011 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 170:3, s. 558-568 Journal article (peer-reviewed)abstract The aim of this study was to characterize the pituitary-interrenal axis in barfin flounder, a flatfish. Adrenocorticotropic hormone (ACTH) and melanocortin 2 receptor (MC2R) have been shown to be indispensable substances in pituitary and interrenal cells for cortisol release, respectively. We previously identified ACTH in the pars distalis of the barfin flounder pituitary gland, and detected transcripts of Mc1r, Mc4r, and Mc5r in the head kidney wherein interrenal cells are located. We have now demonstrated the presence of MC2R, which is a specific receptor for ACTH, in interrenal cells by molecular cloning of Mc2r cDNA and in situ hybridization, and confirmation of the in vitro cortisol-releasing activity of ACTH. These results show the presence of a classical pituitary-interrenal axis in this fish. We also evaluated the role of α-melanocyte-stimulating hormone (α-MSH) and its related peptides. In situ hybridization was used to demonstrate the expression of Mc5r in interrenal cells; both desacetyl-α-MSH and diacetyl-α-MSH showed in vitro cortisol-releasing activities, while the activity of α-MSH was negligible. These findings indicate the presence of an additional pituitary-interrenal axis consisting of α-MSH-like peptides secreted from the neurointermediate lobe of the pituitary and MC5R in the interrenal cells. The cortisol-releasing activity of desacetyl-α-MSH and diacetyl-α-MSH, compared with the low activity of α-MSH, suggest a unique and specific functional role of these forms of MSH peptides. The interrenal co-expression of two subtypes of Mcrs may play a role in this specialization.
22.	Larhammar, Dan, et al. (author) Peptide hormone and receptor evolution 2007 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 153:1-3, s. 147- Journal article (peer-reviewed)abstract An important and fascinating theme that unifies both invertebrate and vertebrate endocrinologists is that of the evolution of peptide precursor and receptor genes. Peptide signalling plays a crucial role in processes that control decisive physiological events in organisms as divergent as yeast and mammals. The majority of small neuronal/endocrine peptides exert their functions via an interaction with heptahelical membrane receptors belonging to the G protein-coupled receptor superfamily, a large and diverse signal transducing protein category which has very ancient evolutionary roots. Most of the larger peptides and growth factors function via other well-conserved receptor classes that contain only a single transmembrane segment. The symposium on peptide hormone and receptor evolution brought together scientists studying peptide–receptor evolution in widely divergent metazoans. Two State-of-the-Art lectures gave overviews of current knowledge of peptide and receptor gene evolution. The sequencing and annotation of entire animal genomes constitutes a very exciting development that have already revolutionized the general views on metazoan macroevolution. The resulting burst of molecular data represents an impressive boost of novel opportunities for comparative and functional genomics research. Several vertebrate peptide and receptor families were described by Dan Larhammar to have multiplied in the 1–2 basal vertebrate tetraploidizations and in a third tetraploidization in ray-finned fishes before the radiation of teleosts. Families proposed to have multiplied in these events include NPY, tachykinins, opioid peptides, as well as the receptors for these three peptide families. The dynamics of coevolutionary change were discussed by Jozef Vanden Broeck based on several examples of peptide–receptor partners that show conservation across the protostomian–deuterostomian barrier. These examples include peptides belonging to the NPY, tachykinin, glycoprotein hormone and insulin-related peptide families, and their respective receptors. Additional examples of coevolution between peptides and their corresponding receptors in insects (the mosquito Aedes aegypti) and chelicerates (the tick Boophilus microplus) were presented by Ron Nachman. His detailed analysis of peptide receptor pharmacology has led to the production and selection of peptidomimetic compounds which specifically activate a particular receptor, while showing enhanced resistance against peptidases. This type of work may ultimately lead to the creation of novel, environmentally safe pest agents for insect management. In two other presentations, the evolution of two quite complex vertebrate peptide receptor systems were discussed. The five divergent and presumably ancient melanocortin receptors found in mammals have only three orthologues in the two sharks investigated so far (Angela Baron). Both the ά-MSH receptor MC1 and the ACTH receptor MC2 still remain to be identified or may have been lost or become widely divergent. The evolution of the large VIP/PACAP/secretin family (Florbela Vieira) involves duplicate PACAP genes in teleost fishes, whereas only a single VIP gene seems to exist. The PACAP gene and its chromosomal environment is more strongly conserved than the VIP gene. Invertebrates only have a single member most closely resembling PACAP. The concluding discussion largely revolved around the proposed tetraploidizations in early vertebrate evolution. While some hesitation still lingers, there is nevertheless no alternative explanation that can account better than the chromosome duplication (and tetraploidization) scenario for the extensive chromosome similarities and the high number of gene duplications that arose before gnathostomatous radiation. Additional gene duplications in early vertebrates were mentioned leading to the somatostatin 2-urotensin II gene pair and the somatostain 1-urotensin II-related peptide gene pair (Hervé Tostivint). Also the possible orthology relationships between peptides described in invertebrates, particularly insects, and vertebrates were discussed. Undoubtedly, definitive orthology relationships of neuropeptide precursor genes between protostomes and deuterostomes are often difficult to determine from sequence comparisons only, and will hopefully be aided by information on chromosome locations and gene neighbours.
23.	Larsson, Tomas, et al. (author) Cloning and sequence analysis of the neuropeptide Y receptors Y5 and Y6 in the coelacanth Latimeria chalumnae 2007 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 150:2, s. 337-342 Journal article (peer-reviewed)abstract Two coelacanth species, Latimeria chalumnae and Latimeria menadoensis, the recently discovered second species, have a key evolutionary position at the divergence of bony fishes and tetrapods. Together with lungfishes, they are the only living species separating the species-rich tetrapods from the other major group of vertebrates, the ray-finned fishes. The coelacanth is therefore of great importance for comparisons of gene families that differ between these two groups, such as the neuropeptide Y (NPY) receptor family. In this work we have sequenced the full-length genes for two NPY receptors in Latimeria chalumnae. Phylogenetic analysis indicated that the two sequences are orthologs of the mammalian Y5 and Y6 receptors. The Y5 gene has been implicated in appetite stimulation in mammals but is absent from teleost fishes. The presence of the Y5 receptor in Latimeria together with phylogenetic analysis shows that Y5 existed before the separation of bony fishes and tetrapods. The Latimeria receptor has about 62 % identity to tetrapod Y5 sequences and contains the extended third intracellular loop with several highly conserved motifs that may be involved in signal transduction. The Latimeria Y6 receptor has about 60% identity to tetrapod Y6 sequences. The functional role of Y6 is unclear as the gene is seemingly functional in some mammals but is non-functional in others. The Y6 receptor is also missing in teleost fishes. Our results confirm an early vertebrate origin for all NPY receptor subtypes presently found in mammals followed by differential gene loss in the different classes of vertebrates.
24.	Lewander, Kerstin, et al. (author) Metabolic effects of insulin in the European eel, Anguilla anguilla L 1976 In: General and Comparative Endocrinology. - 0016-6480 .- 1095-6840. ; 29:4, s. 455-467 Journal article (peer-reviewed)abstract Eels were injected intraperitoneally with insulin (100 IU/kg) and during 14 days the effects on different metabolites in blood, liver and muscle were studied. Exogenous insulin had a marked effect on carbohydrate metabolism. The observed changes (hypoglycemia, depletion of hepatic glycogen and an initial increase in muscle glycogen formation) indicate that insulin in eels induces effects on carbohydrate metabolism qualitatively similar to those found in mammals. Insulin also appears to have an important function in the regulation of lipid metabolism in eels, indicated by a rapid decrease in plasma FFA and a somewhat delayed decrease in other blood lipids. Protein metabolism and plasma inorganic ions were only slightly affected after insulin injection.
25.	Li, B, et al. (author) Expression of nerve growth factor and its receptors TrkA and p75 in the uterus of wild female ground squirrel (Citellus dauricus Brandt) 2012 In: General and comparative endocrinology. - : Elsevier BV. - 1095-6840 .- 0016-6480. ; 176:1, s. 62-69 Journal article (peer-reviewed)
26.	Liang, Jianxin, et al. (author) Mechanistic study of transcription factor Sox18 during heart development 2024 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 350 Journal article (peer-reviewed)abstract Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.
27.	Liu, Ka-Cheuk, et al. (author) Differential regulation of gonadotropin receptors (fshr and lhcgr) by epidermal growth factor (EGF) in the zebrafish ovary 2013 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 181, s. 288-294 Journal article (peer-reviewed)
28.	Liu, Ka-Cheuk, et al. (author) Luteinizing hormone receptor (lhcgr) as a marker gene for characterizing estrogenic endocrine-disrupting chemicals in zebrafish ovarian follicle cells 2013 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 192, s. 89-94 Journal article (peer-reviewed)
29.	Liu, Ka-Cheuk, et al. (author) Spatiotemporal expression analysis of nuclear estrogen receptors in the zebrafish ovary and their regulation in vitro by endocrine hormones and paracrine factors 2017 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 246, s. 218-225 Journal article (peer-reviewed)
30.	Lofgren, Magnus, et al. (author) The influence of social subordinate housing on the withdrawal effects from progesterone and estradiol in male rats 2012 In: General and Comparative Endocrinology. - San Diego : Elsevier BV. - 0016-6480 .- 1095-6840. ; 177:1, s. 62-69 Journal article (peer-reviewed)abstract Chronic stress and its concomitant neurobiological consequences are, in all probability, provocateurs of mental disease in humans. To gain some insight into the provocative effects of stress on hormonally dependent conditions, we developed a rat model that combines social subordinate housing (SSH) with withdrawal from combined progesterone (P) and estradiol (E) treatment (PEVVD). At the start of the experiment, male Wistar rats were housed in triads consisting of one younger rat (35 days old) and two older rats (55 days old), with the intent of producing subordination stress in the younger animals. Triads containing three 35-day-old rats were used as age controls. Subordination stress was assessed with the elevated plus maze (EPM) and by corticosterone (CORT) analysis. Social rank within the triads was determined using a food competition test (FCT) and a tube test (TT). The younger rats (subordinate) and the dominant rats were assigned to 10 days of treatment with 5 mg/kg P combined with 10 mu g/kg E, or placebo (vehicle). Twenty-four hours after the last injection, the subordinate and dominant animals were tested in an open-field test (OFT) and a social challenge test (SCT). The SCT consisted of a 10-min exposure to three unfamiliar rats. SSH increased baseline CORT levels and reduced EPM open-arm time and post-EPM CORT levels compared to age-control rats. Only in the subordinate animals did PEWD increase locomotor activity and digging behavior, and reduce wrestling and pinning behavior. The behavioral results indicate an interaction between the effects of the lasting social subordinate stress and PEWD.
31.	Maranesi, Margherita, et al. (author) Resistin in endocrine pancreas of sheep : Presence and expression related to different diets 2024 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 348 Journal article (peer-reviewed)abstract Resistin (RETN), a recently discovered adipokine, is a cysteine-rich and secretory protein produced by adipocytes. RETN has been detected in several tissues, including human and laboratory animals' pancreas, wherein impairs glucose tolerance and insulin (INS) action and causes INS resistance. This study aims to evaluate the presence and expression of RETN in the pancreas of 15 adult female sheep reared on Apennine pastures, which show a decrease in their nutritional value due to the drought stress linked to the increasing summer aridity. The sheep were divided into 3 groups according to the diet they were subjected to: maximum pasture flowering (MxF) group, maximum pasture dryness (MxD) group, and experimental (Exp) group which received a feed supplementation in addition to the MxD group feeding. Immunohistochemistry and immunofluorescence were performed on formalin-fixed and paraffin-embedded sections of the pancreas to detect the RETN presence and to evaluate the co-localization of RETN with both glucagon (GCG)- and INS-producing cells. In addition, the expression of the three molecules was evaluated also in relation to different diets. RETN was observed only in the endocrine pancreas, showing a wide distribution throughout the pancreatic islets with few negative cells and the RETN producing cells colocalized with both alpha cells and ss cells. No differences in distribution and immunostaining intensity of RETN, GCG and INS were observed among the three groups. Quantitative PCR showed the expression of RETN, GCG and INS in all tested samples. No significant differences were observed for RETN and GCG among all three groups of sheep. Instead, a high statistically significant expression of INS was detected in the MxF group with respect to the Exp and MxD groups. These results highlight the localization of RETN in GCG- and INS-secreting cells involved in glucose homeostasis suggesting a modulatory role for RETN. Furthermore, the RETN expression is not influenced by food supplementation and thus is not affected by diet.
32.	Marcial Lopez, Agustina, et al. (author) Persistently expressed human chorionic gonadotropin induces premature luteinization and progressive alterations on the reproductive axis in female mice. 2023 In: General and comparative endocrinology. - : Elsevier BV. - 1095-6840 .- 0016-6480. ; 336 Journal article (peer-reviewed)abstract The hypothalamic-pituitary-gonadal axis plays a fundamental role in the endocrine regulation of the reproductive function in mammals. Any change in the function of the participating hormones or their receptors can lead to alterations in sexual differentiation, the onset of puberty, infertility, cancer development, and other dysfunctions. In this study, we analyzed the influence of persistently elevated levels of the human chorionic gonadotropin hormone (hCG), a powerful agonist of pituitary luteinizing hormone (LH), on the reproductive axis of female mice. As a consequence of chronic hCG hypersecretion through a global expression of the hCGbeta-subunit in transgenic (TG) female mice, a series of events perturbed the prepubertal to juvenile transition. The imbalance in gonadotropin action was first manifested by precocious puberty and alterations in gonadal hormone production, with the consequent ovarian function disruption and infertility in adulthood. The expansion of cumulus cells in vivo and in vitro, ovulatory capacity, and gene expression of ovulation-related marker genes after hormone stimulation were normal in 3-week-old TG females. However, the expression of genes related to steroidogenesis and luteinization such as Lhcgr, Prlr, and the steroidogenic enzymes Cyp11a1, Cyp17a1, and Cyp19a1 were significantly elevated in the TG females. This study demonstrates that the excessive secretion of hCG in concert with high prolactin, induced premature luteinization, and enhanced ovarian steroidogenesis, as was shown by the up-regulation of luteal cell markers and progesterone synthesis in the TG mice. Furthermore, progressively impaired reproductive function of the TG females occurred from the peripubertal stage to adulthood, thus culminating in infertility.
33.	Mattsson, Anna, et al. (author) Activation of estrogen receptor alpha disrupts differentiation of the reproductive organs in chicken embryos 2011 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 172:2, s. 251-259 Journal article (peer-reviewed)abstract Gonadal estrogen plays an important role in the differentiation of a female phenotype in birds. Exogenous compounds that interfere with estrogen signaling, for instance by binding to the estrogen receptors alpha and beta (ER alpha and ER beta), are therefore potential disruptors of sexual differentiation in birds. The ER alpha agonist propyl-pyrazole-triol (PPT), the ER alpha antagonist methyl piperidino pyrazole (MPP) and the ER beta agonist diarylproprionitrile (DPN) were used in the present study to explore the roles of the ERs in normal and disrupted sex differentiation in the chicken embryo. Activation of ER alpha by PPT caused disturbed differentiation of the reproductive organs in both sexes. In male embryos, PPT caused left-side ovotestis formation and retention of the Mullerian ducts. In female embryos, PPT caused retention of the right Mullerian duct (which normally regresses) and malformation of both Mullerian ducts. PPT also induced hepatic expression of mRNA for the estrogen-regulated egg yolk protein apoVLDL II. Notably, none of these effects were observed following treatment with DPN. ER alpha-inactivation by MPP counteracted the action of PPT but had little effect by its own. Our results indicate that ER alpha plays an important role in sex differentiation of the reproductive tract in female chicken embryos and show that ERa can mediate xenoestrogen-induced disturbances of sex differentiation.
34.	Mattsson, Anna, et al. (author) Selective activation of estrogen receptor alpha in Japanese quail embryos affects reproductive organ differentiation but not the male sexual behavior or the parvocellular vasotocin system 2008 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 159:2-3, s. 150-157 Journal article (peer-reviewed)abstract Estradiol is crucial for normal female differentiation in birds. Developmental effects of estrogen are believed to be mediated by slow genomic actions through the nuclear estrogen receptors alpha (ERα) and/or beta (ERβ). Consequently, exogenous compounds that interfere with the ERs may disrupt sexual differentiation of the reproductive organs and of the brain areas controlling sexual behaviors. The present study was conducted to elucidate the role of ERα in xenoestrogen-induced disruption of sexual differentiation in the Japanese quail (Coturnix japonica). Embryonic treatment with the synthetic estrogen, ethinylestradiol (EE2), and with the ERα-selective agonist, propyl pyrazole triol (PPT), induced oviductal malformations in females and retention of oviducts in males. Both EE2 and PPT caused weight asymmetry between left and right testes and reduced the cloacal gland area in males. EE2 significantly reduced the copulatory behavior in males whereas PPT had no effect on this behavior. The sexually dimorphic parvocellular vasotocin-immunoreactive (VT-ir) system in the medial preoptic nucleus (POM), the lateral septum (SL) and the medial part of the nucleus of the stria terminalis (BSTm), was not affected by EE2 or PPT. Our results suggest that xenoestrogen-induced effects on reproductive organ differentiation are mediated by ERα, whereas demasculinization of male copulatory behavior and the VT-ir system appears not to be induced by activation of ERα alone.
35.	Monette, Michelle Y, et al. (author) Effects of short-term acid and aluminum exposure on the parr-smolt transformation in Atlantic salmon (Salmo salar): disruption of seawater tolerance and endocrine status. 2008 In: General and comparative endocrinology. - : Elsevier BV. - 1095-6840 .- 0016-6480. ; 158:1, s. 122-30 Journal article (peer-reviewed)abstract Episodic acidification resulting in increased acidity and inorganic aluminum (Al(i)) is known to interfere with the parr-smolt transformation of Atlantic salmon (Salmo salar), and has been implicated as a possible cause of population decline. To determine the extent and mechanism(s) by which short-term acid/Al exposure compromises smolt development, Atlantic salmon smolts were exposed to either control (pH 6.7-6.9) or acid/Al (pH 5.4-6.3, 28-64 microgl(-1) Al(i)) conditions for 2 and 5 days, and impacts on freshwater (FW) ion regulation, seawater (SW) tolerance, plasma hormone levels and stress response were examined. Gill Al concentrations were elevated in all smolts exposed to acid/Al relative to controls confirming exposure to increased Al(i). There was no effect of acid/Al on plasma ion concentrations in FW however, smolts exposed to acid/Al followed by a 24h SW challenge exhibited greater plasma Cl(-) levels than controls, indicating reduced SW tolerance. Loss of SW tolerance was accompanied by reductions in gill Na(+),K(+)-ATPase (NKA) activity and Na(+),K(+),2Cl(-) (NKCC) cotransporter protein abundance. Acid/Al exposure resulted in decreased plasma insulin-like growth factor (IGF-I) and 3,3',5'-triiodo-l-thyronine (T(3)) levels, whereas no effect of treatment was seen on plasma cortisol, growth hormone (GH), or thyroxine (T(4)) levels. Acid/Al exposure resulted in increased hematocrit and plasma glucose levels in FW, but both returned to control levels after 24h in SW. The results indicate that smolt development and SW tolerance are compromised by short-term exposure to acid/Al in the absence of detectable impacts on FW ion regulation. Loss of SW tolerance during short-term acid/Al exposure likely results from reductions in gill NKA and NKCC, possibly mediated by decreases in plasma IGF-I and T(3).
36.	Nässel, Dick R., et al. (author) Insulin/IGF signaling and its regulation in Drosophila 2015 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 221, s. 255-266 Journal article (peer-reviewed)abstract Taking advantage of Drosophila as a genetically tractable experimental animal much progress has been made in our understanding of how the insulin/IGF signaling (IS) pathway regulates development, growth, metabolism, stress responses and lifespan. The role of IIS in regulation of neuronal activity and behavior has also become apparent from experiments in Drosophila. This review briefly summarizes these functional roles of IIS, and also how the insulin producing cells (IPCs) are regulated in the fly. Furthermore, we discuss functional aspects of the spatio-temporal production of eight different insulin-like peptides (DILP1-8) that are thought to act on one known receptor (dInR) in Drosophila.
37.	Ocampo Daza, Daniel, 1984-, et al. (author) Evolution of the growth hormone, prolactin, prolactin 2 and somatolactin family 2018 In: General and Comparative Endocrinology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0016-6480 .- 1095-6840. ; 264, s. 94-112 Journal article (peer-reviewed)abstract Growth hormone (GH), prolactin (PRL), prolactin 2 (PRL2) and somatolactin (SL) belong to the same hormone family and have a wide repertoire of effects including development, osmoregulation, metabolism and stimulation of growth. Both the hormone and the receptor family have been proposed to have expanded by gene duplications in early vertebrate evolution. A key question is how hormone-receptor preferences have arisen among the duplicates. The first step to address this is to determine the time window for these duplications. Specifically, we aimed to see if duplications resulted from the two basal vertebrate tetraploidizations (1R and 2R). GH family genes from a broad range of vertebrate genomes were investigated using a combination of sequence-based phylogenetic analyses and comparisons of synteny. We conclude that the PRL and PRL2 genes arose from a common ancestor in 1R/2R, as shown by neighboring gene families. No other gene duplicates were preserved from these tetraploidization events. The ancestral genes that would give rise to GH and PRL/PRL2 arose from an earlier duplication; most likely a local gene duplication as they are syntenic in several species. Likewise, some evidence suggests that SL arose from a local duplication of an ancestral GH/SL gene in the same time window, explaining the lack of similarity in chromosomal neighbors to GH, PRL or PRL2. Thus, the basic triplet of ancestral GH, PRL/ PRL2 and SL genes appear to be unexpectedly ancient. Following 1R/2R, only SL was duplicated in the teleost-specific tetraploidization 3R, resulting in SLa and SLb. These time windows contrast with our recent report that the corresponding receptor genes GHR and PRLR arose through a local duplication in jawed vertebrates and that both receptor genes duplicated further in 3R, which reveals a surprising asynchrony in hormone and receptor gene duplications.
38.	Ocampo Daza, Daniel, 1984-, et al. (author) Evolution of the receptors for growth hormone, prolactin, erythropoietin and thrombopoietin in relation to the vertebrate tetraploidizations 2018 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 257, s. 143-160 Journal article (peer-reviewed)abstract The receptors for the pituitary hormones growth hormone (GH), prolactin (PRL) and somatolactin (SL), and the hematopoietic hormones erythropoietin (EPO) and thrombopoietin (TPO), comprise a structurally related family in the superfamily of cytokine class-I receptors. GH, PRL and SL receptors have a wide variety of effects in development, osmoregulation, metabolism and stimulation of growth, while EPO and TPO receptors guide the production and differentiation of erythrocytes and thrombocytes, respectively. The evolution of the receptors for GH, PRL and SL has been partially investigated by previous reports suggesting different time points for the hormone and receptor gene duplications. This raises questions about how hormone-receptor partnerships have emerged and evolved. Therefore, we have investigated in detail the expansion of this receptor family, especially in relation to the basal vertebrate (1R, 2R) and teleost (3R) tetraploidizations. Receptor family genes were identified in a broad range of vertebrate genomes and investigated using a combination of sequence-based phylogenetic analyses and comparative genomic analyses of synteny. We found that 1R most likely generated EPOR/TPOR and GHR/PRLR ancestors; following this, 2R resulted in EPOR and TPOR genes. No GHR/PRLR duplicate seems to have survived after 2R. Instead the single GHR/PRLR underwent a local duplication sometime after 2R, generating separate syntenic genes for GHR and PRLR. Subsequently, 3R duplicated the gene pair in teleosts, resulting in two GHR and two PRLR genes, but no EPOR or TPOR duplicates. These analyses help illuminate the evolution of the regulatory mechanisms for somatic growth, metabolism, osmoregulation and hematopoiesis in vertebrates.
39.	Ocampo Daza, Daniel, et al. (author) The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes 2012 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 175:1, s. 135-143 Journal article (peer-reviewed)abstract The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes.
40.	Olsén, K Håkan, et al. (author) Endocrine and milt responses of male crucian carp (Carassius carassius L.) to periovulatory females under field conditions 2006 In: General and Comparative Endocrinology. - : Academic Press. - 0016-6480 .- 1095-6840. ; 149:3, s. 294-302 Journal article (peer-reviewed)abstract Laboratory studies in domesticated goldfish (Carassius auratus) show that, during the preovulatory luteinizing hormone (LH) surge, females release a complex steroidal pheromone that induces in males a rapid increase of plasma LH, which in turn increases strippable milt (sperm and seminal fluid) prior to ovulation and spawning. The objective of this study was to determine if the same phenomenon occurs in a wild congener, the crucian carp (Carassius carassius), under field conditions where fish are held in natural waters under ambient temperature and photoperiod. During the spawning season in June 2003, crucian carp were trapped in a small pond near Uppsala, Sweden, and held separately by sex in floating net pens. Addition of untreated females to male pens did not change male LH concentrations or milt volume during the 17 h sampling period. In contrast.. addition of females injected with Ovaprim (TM) (to induce an LH surge and ovulation) increased male LH concentrations at all sample times (5, 9, 13, and 17 h) following female addition and increased milt volumes at all but the first (5 h) sample time. Similar increases in male LH and milt that also occurred when untreated females ovulated spontaneously after addition to male pens suggest it is female ovulatory condition, rather than injection of ovaprim per se, that induced male LH and milt responses. Males also increased LH and milt 9 It after addition of females injected with the goldfish pheromonal steroid 4-pregnen-17,20 beta-diol-3-one (17,20 beta P), suggesting that similar responses to ovaprim-injected females were due, at least in part, to release of preovulatory pheromonal steroid(s). The clear and consistent effects of ovulatory females on male LH and milt, and the fact that crucian carp adapted well to confinement.. ovulated spontaneously, and exhibited apparently normal spawning behavior, all suggest that this species can serve as a useful cyprinid model to study reproductive processes in natural conditions.
41.	Porseryd, Tove, et al. (author) Testis transcriptome alterations in zebrafish (Danio rerio) with reduced fertility due to developmental exposure to 17α-ethinyl estradiol 2018 In: General and Comparative Endocrinology. - : Academic Press. - 0016-6480 .- 1095-6840. ; 262, s. 44-58 Journal article (peer-reviewed)abstract 17α-Ethinylestradiol (EE2) is a ubiquitous aquatic contaminant shown to decrease fish fertility at low concentrations, especially in fish exposed during development. The mechanisms of the decreased fertility are not fully understood. In this study, we perform transcriptome analysis by RNA sequencing of testes from zebrafish with previously reported lowered fertility due to exposure to low concentrations of EE2during development. Fish were exposed to 1.2 and 1.6 ng/L (measured concentration; nominal concentrations 3 and 10 ng/L) of EE2 from fertilization to 80 days of age, followed by 82 days of remediation in clean water. RNA sequencing analysis revealed 249 and 16 genes to be differentially expressed after exposure to 1.2 and 1.6 ng/L, respectively; a larger inter-sample variation was noted in the latter. Expression of 11 genes were altered by both exposures and in the same direction. The coding sequences most affected could be categorized to the putative functions cell signalling, proteolysis, protein metabolic transport and lipid metabolic process. Several homeobox transcription factors involved in development and differentiation showed increased expression in response to EE2 and differential expression of genes related to cell death, differentiation and proliferation was observed. In addition, several genes related to steroid synthesis, testis development and function were differentially expressed. A number of genes associated with spermatogenesis in zebrafish and/or mouse were also found to be differentially expressed. Further, differences in non-coding sequences were observed, among them several differentially expressed miRNA that might contribute to testis gene regulation at post-transcriptional level. This study has generated insights of changes in gene expression that accompany fertility alterations in zebrafish males that persist after developmental exposure to environmental relevant concentrations of EE2 that persist followed by clean water to adulthood. Hopefully, this will generate hypotheses to test in search for mechanistic explanations.
42.	Pradhan, Ajay, 1983-, et al. (author) Germ cell depletion in zebrafish leads to incomplete masculinization of the brain 2018 In: General and Comparative Endocrinology. - : Academic Press. - 0016-6480 .- 1095-6840. ; 265:SI, s. 15-21 Journal article (peer-reviewed)abstract Zebrafish sex differentiation is under the control of multiple genes, but also relies on germ cell number for gonadal development. Morpholino and chemical mediated germ cell depletion leads to sterile male development in zebrafish. In this study we produced sterile males, using a dead end gene morpholino, to determine gonadal-brain interactions. Germ cell depletion following dnd inhibition downregulated the germ cell markers, vasa and ziwi, and later the larvae developed as sterile males. Despite lacking proper testis, the gonadal 11-ketotestosterone (11-KT) and estradiol (E2) levels of sterile males were similar to wild type males. Qualitative analysis of sexual behavior of sterile males demonstrated that they behaved like wild type males. Furthermore, we observed that brain 11-KT and E2 levels in sterile males remained the same as in the wild type males. In female brain, 11-KT was lower in comparison to wild type males and sterile males, while E2 was higher when compared to wild type males. qRT-PCR analysis revealed that the liver transcript profile of sterile adult males was similar to wild type males while the brain transcript profile was similar to wild type females. The results demonstrate that proper testis development may not be a prerequisite for male brain development in zebrafish but that it may be needed to fully masculinize the brain.
43.	Pradhan, Ajay, 1983-, et al. (author) Inhibition of retinoic acid synthesis disrupts spermatogenesis and fecundity in zebrafish 2015 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 217, s. 81-91 Journal article (peer-reviewed)abstract Timing of germ cell entry into meiosis is sexually dimorphic in mammals. However it was recently shown that germ cells initiate meiosis at the same time in male and female zebrafish. Retinoic acid (RA) has been shown to be critical for mammalian spermatogenesis. Inhibition of RA synthesis by WIN 18,446 has been reported to inhibit spermatogenesis in a wide variety of animals including humans and was once used as a contraceptive in humans. In this study we explored the role of RA in zebrafish spermatogenesis. In silico analysis with Internal coordinate mechanics docking software showed that WIN 18,446 can bind to the rat, human and zebrafish Aldh1a2 catalytic domain with equivalent potency. RA exposure resulted in upregulation of the RA metabolizing enzyme genes cyp26a1, cyp26b1 and cyp26c1 in vitro and in vivo. Exposure to WIN 18,446 resulted in down-regulation of Aldh1a2, cyp26a1 and cyp26b1 in vivo. WIN 18,446 was effective in disrupting spermatogenesis and fecundity in zebrafish but the reduction in sperm count and fecundity was only observed when zebrafish were maintained on a strict Artemia nauplii diet which is known to contain low levels of vitamin A. This study shows that RA is involved in spermatogenesis as well as oocyte development in zebrafish. As the zebrafish Aldh1a2 structure and function is similar to the mammalian counterpart, Aldh1a2 inhibitor screening using zebrafish as a model system may be beneficial in the discovery and development of new and safe contraceptives for humans.
44.	Rosengren, Malin, 1982, et al. (author) The brain-gut axis of fish: Rainbow trout with low and high cortisol response show innate differences in intestinal integrity and brain gene expression 2018 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 257, s. 235-245 Journal article (peer-reviewed)abstract © 2017 Elsevier Inc. In fish, the stress hormone cortisol is released through the action of the hypothalamic pituitary interrenal axis (HPI-axis). The reactivity of this axis differs between individuals and previous studies have linked this to different behavioural characteristics and stress coping styles. In the current study, low and high responding (LR and HR) rainbow trout in terms of cortisol release during stress were identified, using a repeated confinements stress test. The expression of stress related genes in the forebrain and the integrity of the stress sensitive primary barrier of the intestine was examined. The HR trout displayed higher expression levels of mineralocorticoid and serotonergic receptors and serotonergic re-uptake pumps in the telencephalon during both basal and stressed conditions. This confirms that HPI-axis reactivity is linked also to other neuronal behavioural modulators, as both the serotonergic and the corticoid system in the telencephalon are involved in behavioural reactivity and cognitive processes. Involvement of the HPI-axis in the brain-gut-axis was also found. LR trout displayed a lower integrity in the primary barrier of the intestine during basal conditions compared to the HR trout. However, following stress exposure, LR trout showed an unexpected increase in intestinal integrity whereas the HR trout instead suffered a reduction. This could make the LR individuals more susceptible to pathogens during basal conditions where instead HR individuals would be more vulnerable during stressed conditions. We hypothesize that these barrier differences are caused by regulation/effects on tight junction proteins possibly controlled by secondary effects of cortisol on the intestinal immune barrier or differences in parasympathetic reactivity.
45.	Roufidou, Chrysoula, et al. (author) Hormonal changes over the spawning cycle in the female three-spined stickleback, Gasterosteus aculeatus 2018 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 257:SI, s. 97-105 Journal article (peer-reviewed)abstract Female three-spined sticklebacks are batch spawners laying eggs in a nest built by the male. We sampled female sticklebacks at different time points, when they were ready to spawn and 6, 24, 48 and 72 hours post-spawning (hps) with a male. Following spawning, almost all females (15 out of 19) had ovulated eggs again at Day 3 post-spawning (72hps). At sampling, plasma, brain and pituitaries were collected, and the ovary and liver were weighed. Testosterone (T) and estradiol (E2) were measured by radioimmunoassay. Moreover, the mRNA levels of follicle-stimulating hormone (fsh-β) and luteinizing hormone (lh-β) in the pituitary, and of the gonadotropin-releasing hormones (GnRHs: gnrh2, gnrh3) and kisspeptin (kiss2) and its G protein-coupled receptor (gpr54) in the brain were measured by real-time qPCR. Ovarian weights peaked in “ready to spawn” females, dropped after spawning, before again progressively increasing from 6 to 72hps. Plasma T levels showed peaks at 24 and 48hps and decreased at 72hps, while E2 levels increased already at 6hps and remained at high levels up to 48hps. There was a strong positive correlation between T and E2 levels over the spawning cycle. Pituitary lh-β mRNA levels showed a peak at 48hps, while fsh-β did not change. The neuropeptides and gpr54 did not show any changes. The changes in T and E2 over the stickleback spawning cycle were largely consistent with those found in other multiple-spawning fishes whereas the marked correlation between T and E2 does not support T having other major roles over the cycle than being a precursor for E2.
46.	Schjolden, Joachim, et al. (author) Melanocortin peptides affect the motivation to feed in rainbow trout (Oncorhynchus mykiss) 2009 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 160:2, s. 134-138 Journal article (peer-reviewed)abstract In this study, we investigated the effects of one melanocortin receptor (MCR) agonist and two antagonists on food intake in juvenile rainbow trout. Baseline food intake was established prior to 1 microl intracerebroventricular injection (ICV) of the non-specific agonist MTII, the MC4R antagonist HS024 and the MC3/4R antagonist SHU9119 at concentrations of 0.3, 1 or 3 nM. Saline-injected fish and untreated fish served as controls. Changes in food intake were observed 1h after the ICV injections. Our results showed that treatment with MTII significantly decreased food intake at 3 nM compared to control, HS024 significantly increased food intake at 3 nM compared to control and saline-treated fish, and SHU9119 significantly increased food intake at 3 nM compared to saline-treated fish. In conclusion, our study provides further evidence, and hence strengthens the hypothesis, that MC4R participates in the control of energy balance in fish in the same manner as in mammals. Our findings that HS024 is more potent than SHU9119 in increasing food intake suggest that the effects of melanocortin on energy balance in rainbow trout are mainly regulated by activation of MC4R. Hence, HS024 seems an excellent tool as a MC4R antagonist in rainbow trout.
47.	Shao, Yi Ta, et al. (author) Androgen feedback effects on LH and FSH, and photoperiodic control of reproduction in male three-spined sticklebacks, Gasterosteus aculeatus 2013 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 182, s. 16-23 Journal article (peer-reviewed)abstract Sexual maturation in the stickleback is controlled by photoperiod. The aim of this study was to find out whether changes in feedback effects exerted by sex steroids could mediate the photoperiodic effect, which is regarded to be of an all-or-nothing character. To that end, males were castrated and treated with different doses of testosterone (T) and in one experiment also with the aromatase inhibitor fadrozole (AI) and kept under different photoperiods. In control fish, long day (LD 16:8) stimulated maturation, associated with more hypertrophied kidneys (a secondary sexual character) and higher levels of pituitary lhb and fshb mRNA than under short day conditions (LD 8:16). Under LD 8:16, low doses of T suppressed both lhb and fshb mRNA levels. However, with the use of high doses of T and/or longer photoperiods the inhibitory effects on lhb and fshb mRNA levels became less clear or instead positive effects were observed. Under intermediate photoperiod conditions, the negative feedback effect of a low dose of T on fshb was more prominent with shorter photoperiods, whereas no such shift was observed for lhb mRNA. The inhibitory effect of the low dose of T on lhb mRNA levels under LD 8:16 was abolished by AI, whereas the stimulatory effect of the high dose of T was not. The negative feedback effects were more marked under short days than under long days, whereas positive feedback effects were more marked under long days. The suppression of both fshb and lhb mRNA levels by low androgen levels, especially under short days, may inhibit maturation completely unless a rise of androgens above threshold levels would allow complete maturation.
48.	Shu, Tingting, et al. (author) Zebrafish cyp17a1 Knockout Reveals that Androgen-Mediated Signaling is Important for Male Brain Sex Differentiation 2020 In: General and Comparative Endocrinology. - : Academic Press. - 0016-6480 .- 1095-6840. ; 295 Journal article (peer-reviewed)abstract Brain sex differentiation is a complex process, wherein genes and steroid hormones act to induce specific gender brain differentiation. Testosterone (T) derived from the gonads has been linked to neural circuit modeling in a sex-specific manner. Previously, we have shown that cyp17a1 knockout (KO) zebrafish have low plasma androgen levels, and display compromised male-typical mating behaviors. In this study, we demonstrated that treatment of cyp17a1 KO males with T or 11-ketotestosterone (11-KT) is sufficient to rescue mating impairment by restoring the male-typical secondary sex characters (SSCs) and mating behaviors, confirming an essential role of androgen in maintaining SSCs and mating behaviors. Brain steroid hormone analysis revealed that cyp17a1 KO fish have reduced levels of T and 11-KT. We performed RNA sequencing on brain samples of control and cyp17a1 KO male zebrafish to get insights regarding the impact of cyp17a1 KO on gene expression pattern, and to correlate it with the observed disruption of male-typical mating behaviors. Transcriptome analysis of cyp17a1 KO males showed a differential gene expression when compared to control males. In total, 358 genes were differentially regulated between control males and KO males. Important genes including brain aromatase (cyp19a1b), progesterone receptor (pgr), deiodinase (dio2), and insulin-like growth factor 1 (igf1) that are involved in brain functions, as well as androgen response genes including igf1, frem1a, elovl1a, pax3a, mmp13b, hsc70, ogg1 were regulated. RT-qPCR analysis following rescue of cyp17a1 KO with T and 11-KT further suggested that androgen-mediated signaling is disrupted in the cyp17a1 KO fish. Our results indicated that cyp17a1 KO fish have an incomplete masculinization and altered brain gene expression, which could be due to decreased androgen levels.
49.	Sundh, Henrik, et al. (author) Environmental salinity regulates the in vitro production of [3H]-1,25-dihydroxyvitamin D3 and [3H]-24,25 dihydroxyvitamin D3 in rainbow trout (Oncorhynchus mykiss) 2007 In: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 152:2-3, s. 252-258 Journal article (peer-reviewed)abstract Previous studies have shown that specific binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) to enterocyte basolateral membranes (BLM), as well as circulating concentrations, is affected in response to changes in environmental salinity. It is not known if the production of 1,25(OH)2D3 and 24,25(OH)2D3 is affected by environmental salinity. The aim of the present study was to measure the in vitro production of [3H]-1,25(OH)2D3 and [3H]-24,25(OH)2D3 in fresh water (FW) and after 1, 2, 3, and 7 days after transfer to seawater (SW). Pooled sub-cellular fractions (mitochondria and microsomes) from liver or kidney was incubated with [3H]-25(OH)D3 and the produced metabolites were separated using HPLC. Hepatic production of [3H]-1,25(OH)2D3 was decreased after 24 h in SW. This was followed by an up-regulation after 48 h and a second, slower decrease in production rate which leveled out after 7 days in SW. The production rate in SW was lower than the original rate in FW-adapted fish. For hepatic [3H]-24,25(OH)2D3 production the pattern was reversed. Renal production of [3H]-24,25(OH)2D3 increased significantly during the period of SW acclimation. These results suggest that environmental salinity regulates the production rate of the two antagonizing calcium regulatory hormones; 1,25(OH)2D3 and 24,25(OH)2D3. This gives further evidence to the hypothesis that there is a physiological regulation and a differentiated importance of 1,25(OH)2D3 and 24,25(OH)2D3 in relation to environmental calcium concentrations.
50.	Sundström, Görel, et al. (author) Characterization of the neuropeptide Y system in the frog Silurana tropicalis (Pipidae) : three peptides and six receptor subtypes 2012 In: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 177:3, s. 322-331 Journal article (peer-reviewed)abstract Neuropeptide Y and its related peptides PYY and PP (pancreatic polypeptide) are involved in feeding behavior, regulation of the pituitary and the gastrointestinal tract, and numerous other functions. The peptides act on a family of G-protein coupled receptors with 4-7 members in jawed vertebrates. We describe here the NPY system of the Western clawed frog Silurana (Xenopus) tropicalis. Three peptides, NPY, PYY and PP, were identified together with six receptors, namely subtypes Y1, Y2, Y4, Y5, Y7 and Y8. Thus, this frog has all but one of the ancestral seven gnathostome NPY-family receptors, in contrast to mammals which have lost 2-3 of the receptors. Expression levels of mRNA for the peptide and receptor genes were analyzed in a panel of 19 frog tissues using reverse transcriptase quantitative PCR. The peptide mRNAs had broad distribution with highest expression in skin, blood and small intestine. NPY mRNA was present in the three brain regions investigated, but PYY and PP mRNAs were not detectable in any of these. All receptor mRNAs had similar expression profiles with high expression in skin, blood, muscle and heart. Three of the receptors, Y5, Y7 and Y8, could be functionally expressed in HEK-293 cells and characterized with binding studies using the three frog peptides. PYY had the highest affinity for all three receptors (K(i) 0.042-0.34 nM). Also NPY and PP bound to the Y8 receptor with high affinity (0.14 and 0.50 nM). The low affinity of NPY for the Y5 receptor (100-fold lower than PYY) differs from mammals and chicken. This may suggest a less important role of NPY on Y5 in appetite stimulation in the frog compared with amniotes. In conclusion, our characterization of the NPY system in S. tropicalis with its six receptors demonstrates not only greater complexity than in mammals but also some interesting differences in ligand-receptor preferences.

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