| 1. |
- Bondesson, Maria, et al.
(author)
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Estrogen receptor signaling during vertebrate development
- 2015
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In: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1849:2, s. 142-151
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Research review (peer-reviewed)abstract
- Estrogen receptors are expressed and their cognate ligands produced in all vertebrates, indicative of important and conserved functions. Through evolution estrogen has been involved in controlling reproduction, affecting both the development of reproductive organs and reproductive behavior. This review broadly describes the synthesis of estrogens and the expression patterns of aromatase and the estrogen receptors, in relation to estrogen functions in the developing fetus and child. We focus on the role of estrogens for the development of reproductive tissues, as well as non-reproductive effects on the developing brain. We collate data from human, rodent, bird and fish studies and highlight common and species-specific effects of estrogen signaling on fetal development. Morphological malformations originating from perturbed estrogen signaling in estrogen receptor and aromatase knockout mice are discussed, as well as the clinical manifestations of rare estrogen receptor alpha and aromatase gene mutations in humans.
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| 2. |
- Dey, Prasenjit, et al.
(author)
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Estrogen Receptor beta 2 Induces Hypoxia Signature of Gene Expression by Stabilizing HIF-1 alpha in Prostate Cancer
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Journal article (peer-reviewed)abstract
- The estrogen receptor (ER) beta variant ER beta 2 is expressed in aggressive castration-resistant prostate cancer and has been shown to correlate with decreased overall survival. Genome-wide expression analysis after ER beta 2 expression in prostate cancer cells revealed that hypoxia was an overrepresented theme. Here we show that ER beta 2 interacts with and stabilizes HIF-1 alpha protein in normoxia, thereby inducing a hypoxic gene expression signature. HIF-1 alpha is known to stimulate metastasis by increasing expression of Twist1 and increasing vascularization by directly activating VEGF expression. We found that ER beta 2 interacts with HIF-1 alpha and piggybacks to the HIF-1 alpha response element present on the proximal Twist1 and VEGF promoters. These findings suggest that at least part of the oncogenic effects of ER beta 2 is mediated by HIF-1 alpha and that targeting of this ER beta 2 -HIF-1 alpha interaction may be a strategy to treat prostate cancer.
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| 3. |
- Heverin, Maura, et al.
(author)
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On the regulatory importance of 27-hydroxycholesterol in mouse liver
- 2017
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In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier. - 0960-0760 .- 1879-1220. ; 169, s. 10-21
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Research review (peer-reviewed)abstract
- 27-Hydroxycholesterol (27OH) is a strong suppressor of cholesterol synthesis and a weak activator of LXR in vitro. The regulatory importance of 27OH in vivo is controversial. Here we utilized male mice with increased levels of 27OH either due to increased production (CYP27A1 transgenic mice) or reduced metabolism (Cyp7b1-/- mice). We also used mice lacking 27OH due to a knockout of Cyp27a1. The latter mice were treated with cholic acid to compensate for reduced bile acid synthesis. The effects of the different levels of 27OH on Srebp- and other LXR-regulated genes in the liver were investigated. In the liver of CYP27tg mice we found a modest increase of the mRNA levels corresponding to the LXR target genes Cyp7b1 and Abca1. A number of other LXR-regulated genes were not affected. The effect on Abca1 mRNA was not seen in the liver of Cyp7b1-/- mice. There were little or no effects on cholesterol synthesis. In the liver of the Cyp27-/- mice treated with 0.025% cholic acid there was no significant effect of the knockout on the LXR target genes. In a previous work triple-knockout mice deficient in the biosynthesis of 24S-hydroxycholesterol, 25-hydroxycholesterol and 27OH were shown to have impaired response to dietary cholesterol, suggesting side-chain oxidized oxysterols to be mediators in cholesterol-induced effects on LXR target genes at a transcriptional level (Chen W. et al., Cell Metab. 5 (2007) 73-79). The hydroxylated oxysterol responsible for the effect was not defined. We show here that treatment of wildtype mice with dietary cholesterol under the same conditions as in the above study induced the LXR target genes Lpl, Abcg8 and Srebp1c in wild type mice but failed to activate the same genes in mice lacking 27-hydroxycholesterol due to a knockout of Cyp27. We failed to demonstrate the above effects at the protein level (Abcg8) or at the activity level (Lpl). The results suggest that 27OH is not an important regulator of Srebp- or LXR regulated genes under basal conditions in mouse liver. On the other hand 27OH appears to mediate cholesterol-induced effects on some LXR target genes at a transcriptional level under some in vivo conditions.
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| 4. |
- Ibrahim, Ahmed, et al.
(author)
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Colitis-induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity
- 2019
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:12, s. 3086-3098
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Journal article (peer-reviewed)abstract
- Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone-replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine-specific deletion of ERβ (ERβKOVil ) were generated using the Cre-LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water. The microbiota population were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples (N = 39). Differences in the microbiota due to AOM/DSS and absence of ERβ were identified through bioinformatic analyses of the 16S-Seq data, and the distribution of bacterial species was corroborated using qPCR. We demonstrate that colitis-induced CRC reduced the gut microbiota diversity and that loss of ERβ enhanced this process. Further, the Bacteroidetes genus Prevotellaceae_UCG_001 was overrepresented in AOM/DSS mice compared to untreated controls (3.5-fold, p = 0.004), and this was enhanced in females and in ERβKOVil mice. Overall, AOM/DSS enriched for microbiota impacting immune system diseases and metabolic functions, and lack of ERβ in combination with AOM/DSS enriched for microbiota impacting carbohydrate metabolism and cell motility, while reducing those impacting the endocrine system. Our data support that intestinal ERβ contributes to a more favorable microbiome that could attenuate CRC development.
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| 5. |
- Jansson, John-Olov, 1954, et al.
(author)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Journal article (peer-reviewed)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 6. |
- Mills, James A., et al.
(author)
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Archiving Primary Data : Solutions for Long-Term Studies
- 2015
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In: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 30:10, s. 581-589
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Journal article (peer-reviewed)abstract
- The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (PIs) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.
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| 7. |
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| 8. |
- Moller, Anders Pape, et al.
(author)
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Effects of interspecific coexistence on laying date and clutch size in two closely related species of hole-nesting birds
- 2018
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In: Journal of Animal Ecology. - : WILEY. - 0021-8790 .- 1365-2656. ; 87:6, s. 1738-1748
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Journal article (peer-reviewed)abstract
- Coexistence between great tits Parus major and blue tits Cyanistes caeruleus, but also other hole-nesting taxa, constitutes a classic example of species co-occurrence resulting in potential interference and exploitation competition for food and for breeding and roosting sites. However, the spatial and temporal variations in coexistence and its consequences for competition remain poorly understood. We used an extensive database on reproduction in nest boxes by great and blue tits based on 87 study plots across Europe and Northern Africa during 1957-2012 for a total of 19,075 great tit and 16,729 blue tit clutches to assess correlative evidence for a relationship between laying date and clutch size, respectively, and density consistent with effects of intraspecific and interspecific competition. In an initial set of analyses, we statistically controlled for a suite of site-specific variables. We found evidence for an effect of intraspecific competition on blue tit laying date (later laying at higher density) and clutch size (smaller clutch size at higher density), but no evidence of significant effects of intraspecific competition in great tits, nor effects of interspecific competition for either species. To further control for site-specific variation caused by a range of potentially confounding variables, we compared means and variances in laying date and clutch size of great and blue tits among three categories of difference in density between the two species. We exploited the fact that means and variances are generally positively correlated. If interspecific competition occurs, we predicted a reduction in mean and an increase in variance in clutch size in great tit and blue tit when density of heterospecifics is higher than the density of conspecifics, and for intraspecific competition, this reduction would occur when density of conspecifics is higher than the density of heterospecifics. Such comparisons of temporal patterns of means and variances revealed evidence, for both species, consistent with intraspecific competition and to a smaller extent with interspecific competition. These findings suggest that competition associated with reproductive behaviour between blue and great tits is widespread, but also varies across large spatial and temporal scales.
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| 9. |
- Shore, Richard, et al.
(author)
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Sex differences and effects of oestrogen in rat gastric mucosal defence
- 2017
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In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 23:3, s. 426-436
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Journal article (peer-reviewed)abstract
- AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence. METHODS Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry. RESULTS The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 +/- 0.12 mL/min.g in males and 0.51 +/- 0.03 mL/min.g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 +/- 1 mu m and 80 +/- 3 mu m respectively. After 60 min the mucus thickness increased to 113 +/- 3 mu m in males and 121 +/- 3 mu m in females with no statistically significant difference seen between the sexes. Following oestrogen administration (0.1 followed by 1 mu g/kg.min), mean blood flow in the gastric mucosa decreased by 31% [68 +/- 13 perfusion units (PFU)] in males which was significantly different compared to baseline (P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 +/- 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 +/- 0.04 to 1.1 +/- 0.1 mL/min.100 g in males and 0.4 +/- 0.3 to 2.1 +/- 0.3 mL/min.100 g in females (P = 0.065)]. There were no significant differences between 17 beta-Estradiol treated males (mean ratio of positive staining +/- SEM) (0.06 +/- 0.07) and females (0.11 +/- 0.11) in the staining of ER alpha (P = 0.24). Also, there were no significant differences between 17 beta-Estradiol treated males (0.18 +/- 0.21) and females (0.06 +/- 0.12) in the staining of ER beta (P = 0.11). Finally, there were no significant differences between 17 beta-Estradiol treated males (0.04 +/- 0.05) and females (0.11 +/- 0.10) in the staining of CGRP (P = 0.14). CONCLUSION Gastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.
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| 10. |
- Vaugoyeau, Marie, et al.
(author)
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Interspecific variation in the relationship between clutch size, laying date and intensity of urbanization in four species of hole-nesting birds
- 2016
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 6:16, s. 5907-5920
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Journal article (peer-reviewed)abstract
- The increase in size of human populations in urban and agricultural areas has resulted in considerable habitat conversion globally. Such anthropogenic areas have specific environmental characteristics, which influence the physiology, life history, and population dynamics of plants and animals. For example, the date of bud burst is advanced in urban compared to nearby natural areas. In some birds, breeding success is determined by synchrony between timing of breeding and peak food abundance. Pertinently, caterpillars are an important food source for the nestlings of many bird species, and their abundance is influenced by environmental factors such as temperature and date of bud burst. Higher temperatures and advanced date of bud burst in urban areas could advance peak caterpillar abundance and thus affect breeding phenology of birds. In order to test whether laying date advance and clutch sizes decrease with the intensity of urbanization, we analyzed the timing of breeding and clutch size in relation to intensity of urbanization as a measure of human impact in 199 nest box plots across Europe, North Africa, and the Middle East (i.e., the Western Palearctic) for four species of hole-nesters: blue tits (Cyanistes caeruleus), great tits (Parus major), collared flycatchers (Ficedula albicollis), and pied flycatchers (Ficedula hypoleuca). Meanwhile, we estimated the intensity of urbanization as the density of buildings surrounding study plots measured on orthophotographs. For the four study species, the intensity of urbanization was not correlated with laying date. Clutch size in blue and great tits does not seem affected by the intensity of urbanization, while in collared and pied flycatchers it decreased with increasing intensity of urbanization. This is the first large-scale study showing a species-specific major correlation between intensity of urbanization and the ecology of breeding. The underlying mechanisms for the relationships between life history and urbanization remain to be determined. We propose that effects of food abundance or quality, temperature, noise, pollution, or disturbance by humans may on their own or in combination affect laying date and/or clutch size.
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| 11. |
- Westerfelt, Per, et al.
(author)
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Nesting of solitary wasps and bees in natural and artificial holes in dead wood in young boreal forest stands
- 2015
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In: Insect Conservation and Diversity. - : Wiley. - 1752-458X .- 1752-4598. ; 8, s. 493-504
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Journal article (peer-reviewed)abstract
- 1. Life history traits of solitary nest provisioning bees and wasps (Aculeata) are characterised by low fecundity and extensive parental care. Therefore, it can be expected that egg-laying females are demanding in their nest choice. 2. Dead wood in young boreal forest stands in mid-Sweden were surveyed for holes made by different insect species and the occupancy of solitary bees or wasps in those holes was analysed. Artificial nests consisting of wooden poles with pre-drilled holes were used for comparison. 3. In 1634 wood objects, 5793 potential nesting holes of 16 types were labelled to insect species or genera that had made the hole. Only 1.8% of these were occupied by any bee or wasp species. In contrast to the natural wood objects, artificial nests had high occupancy (c. 30%). 4. Hole diameter, rather than tree species, hole type or stand age, was the most important factor explaining occupancy of a certain aculeate species. Holes in standing dead wood (SDW) had higher occupancy than holes in stumps and logs. 5. The results are discussed in the context of aculeate life history traits. It is argued that the reason for the low occupancy in the natural dead wood, espe- cially in the stumps, was that most holes were situated in moist and decayed wood, and offered inferior conditions for offspring during the development from egg to adult. 6. Retention and creation of SDW objects of different tree species at final felling is recommended.
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