| 1. |
- Liang, Jianxin, et al.
(författare)
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Mechanistic study of transcription factor Sox18 during heart development
- 2024
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 350
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Maranesi, Margherita, et al.
(författare)
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Resistin in endocrine pancreas of sheep : Presence and expression related to different diets
- 2024
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Ingår i: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 348
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Marcial Lopez, Agustina, et al.
(författare)
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Persistently expressed human chorionic gonadotropin induces premature luteinization and progressive alterations on the reproductive axis in female mice.
- 2023
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Ingår i: General and comparative endocrinology. - : Elsevier BV. - 1095-6840 .- 0016-6480. ; 336
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Shu, Tingting, et al.
(författare)
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Zebrafish cyp17a1 Knockout Reveals that Androgen-Mediated Signaling is Important for Male Brain Sex Differentiation
- 2020
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Ingår i: General and Comparative Endocrinology. - : Academic Press. - 0016-6480 .- 1095-6840. ; 295
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Vargas-Chacoff, L., et al.
(författare)
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Effects of long-term cortisol treatment on growth and osmoregulation of Atlantic salmon and brook trout
- 2021
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480. ; 308
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Tidskriftsartikel (refereegranskat)abstract
- Cortisol is the final product of the hypothalamic-pituitary-interrenal (HPI) axis and acts as a gluco- and mineralocorticoid in fish. Long-term elevations of cortisol have been linked to reduced growth in fishes, but the mechanism(s) and relative sensitivities of species are still unclear. We carried out experiments to examine the relative effects of cortisol on growth and gill NKA activity in two salmonids: Atlantic salmon (Salmo salar) and brook trout (Salvelinus fontinalis). Treatment with intraperitoneal cortisol implants for 30 days resulted in reduced growth in both species, but with greater sensitivity to cortisol in brook trout. Gill NKA activity was strongly upregulated by cortisol in Atlantic salmon, and weakly upregulated in brook trout but with no statistically significant effect. Cortisol treatment resulted in reduced plasma levels of insulin-like growth factor I and increased plasma growth hormone levels in Atlantic salmon. Our results demonstrate that there are species differences in the sensitivity of growth and osmoregulation to cortisol, even among species in the same family (Salmonidae).
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