Recent studies have suggested that the hypothalamus has an important role in aging by regulating nuclear factor-?B (NF-?B)-directed gonadotropin-releasing hormone (GnRH) decline. Moreover, our previous study has shown that ischemia-reperfusion (IR) injury activates NF-?B to reduce hypothalamic GnRH release, thus suggesting that IR injury may facilitate hypothalamic programming of system aging. In this study, we further examined the role of phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) pathway, a critical intracellular signal pathway involved in the repair process after IR, in hypoxia-reoxygenation (HR)-associated GnRH decline in vitro. We used GT1-7 cells and primarily-cultured mouse GnRH neurons as cell models for investigation. Our data revealed that the activation of the PI3K/Akt/Forkhead box protein O3a (FOXO3a) pathway protects GnRH neurons from HR-induced GnRH decline by preventing HR-induced gnrh1 gene inhibition and NF-?B activation. Our results further the understanding of the regulatory mechanisms of HR-associated hypothalamic GnRH decline.
- MeSH
- 1-fosfatidylinositol-3-kinasa metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- hormon uvolňující gonadotropiny * genetika metabolismus farmakologie MeSH
- hypothalamus metabolismus MeSH
- hypoxie metabolismus MeSH
- myši MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- galanin fyziologie MeSH
- gastrointestinální hormony fyziologie MeSH
- hormon uvolňující gonadotropiny analýza metabolismus MeSH
- hormon uvolňující kortikotropin analýza metabolismus MeSH
- hypothalamus fyziologie metabolismus MeSH
- inzulin fyziologie metabolismus MeSH
- leptin analýza metabolismus MeSH
- lidé MeSH
- mentální anorexie metabolismus patofyziologie MeSH
- neuropeptid Y fyziologie MeSH
- neurosekreční systémy fyziologie patofyziologie MeSH
- obezita etiologie metabolismus patofyziologie MeSH
- orexiny fyziologie metabolismus MeSH
- poruchy příjmu potravy etiologie metabolismus patofyziologie MeSH
- regulace chuti k jídlu fyziologie MeSH
- systém hypotalamus-hypofýza patofyziologie MeSH
- tuková tkáň chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
This review is focused on the physiological and pathophysiological relevance of steroids influencing the activities of the central and peripheral nervous systems with regard to their concentrations in body fluids and tissues in various stages of human life like the fetal development or pregnancy. The data summarized in this review shows that DHEA and its unconjugated and sulfated metabolites are physiologically and pathophysiologically relevant in modulating numerous ion channels and participate in vital functions of the human organism. DHEA and its unconjugated and sulfated metabolites including 5α/β-reduced androstane steroids participate in various physiological and pathophysiological processes like the management of GnRH cyclic release, regulation of glandular and neurotransmitter secretions, maintenance of glucose homeostasis on one hand and insulin insensitivity on the other hand, control of skeletal muscle and smooth muscle activities including vasoregulation, promotion of tolerance to ischemia and other neuroprotective effects. In respect of prevalence of steroid sulfates over unconjugated steroids in the periphery and the opposite situation in the CNS, the sulfated androgens and androgen metabolites reach relevance in peripheral organs. The unconjugated androgens and estrogens are relevant in periphery and so much the more in the CNS due to higher concentrations of most unconjugated steroids in the CNS tissues than in circulation and peripheral organs. This article is part of a Special Issue entitled "Essential role of DHEA".
- MeSH
- centrální nervový systém metabolismus MeSH
- dehydroepiandrosteron fyziologie MeSH
- glukosa metabolismus MeSH
- hladké svalstvo metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- iontové kanály fyziologie MeSH
- kosterní svaly metabolismus MeSH
- lidé MeSH
- periferní nervový systém metabolismus MeSH
- steroidy metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100, 400 and 800 μg/L VZ and 5 μg/L 17β-estradiol (E2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 μg/L VZ, while it was increased in goldfish exposed to 100 μg/L VZ after 30 days of exposure. Circulating E2 level was unchanged in VZ treated goldfish, however the E2/11-KT ratio was increased in a concentration-related manner. In E2 treated goldfish, circulatory 11-KT and E2 levels were decreased and increased, respectively, which resulted in an increase in the E2/11-KT ratio. Exposure to VZ at 100 μg/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3β-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish.
- MeSH
- aromatasa metabolismus MeSH
- chemické látky znečišťující vodu aplikace a dávkování toxicita MeSH
- estradiol metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- hypofýza účinky léků metabolismus MeSH
- játra účinky léků metabolismus MeSH
- karas zlatý * MeSH
- oxazoly aplikace a dávkování toxicita MeSH
- rozmnožování účinky léků fyziologie MeSH
- testis účinky léků metabolismus MeSH
- vitelogeniny metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Two forms of gonadotropin-releasing hormone (GnRH), GnRH-I and GnRH-II, are commonly present in mammals. The main hormone controlling reproduction is GnRH-I acting through its receptor (GnRHR-I), whereas the function of GnRH-II is unknown. In primates, it has been suggested that GnRH-II is a specific agonist for the structurally distinct GnRHR-II. Here we compared effects of GnRH-I and GnRH-II on intracellular calcium and gonadotropin hormone release in neonatal rat gonadotrophs in vitro and the dependence of agonist actions on cyclic nucleotide levels. Both agonists elevated intracellular calcium and stimulated gonadotropin secretion in a concentration-dependent manner, with comparable peak amplitudes, but GnRH-I was three times more potent than GnRH-II. Antide, a specific GnRHRI antagonist, completely blocked the action of both agonists on gonadotropin release. Inhibition of adenylyl cyclase activity by melatonin and MDL significantly attenuated GnRH-I- and GnRHII- induced calcium signaling and gonadotropin release, whereas inhibition of soluble guanylyl cyclase activity was ineffective. GnRH-II also generated calcium oscillations in a fraction of gonadotrophs not expressing melatonin receptors. These results indicate that GnRH-I and GnRH-II act on the same GnRHR to stimulate gonadotropin release through intracellular calcium and cyclic nucleotide signaling, and that GnRH-II is less potent agonist for this receptor in neonatal rat gonadotrophs.
- MeSH
- adenylátcyklasy metabolismus MeSH
- gonadotropní buňky metabolismus sekrece MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- inhibitory adenylylcyklasy MeSH
- krysa rodu rattus MeSH
- luteinizační hormon sekrece MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- protein - isoformy metabolismus MeSH
- vápníková signalizace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- gonadotropiny fyziologie metabolismus MeSH
- hormon uvolňující gonadotropiny fyziologie metabolismus MeSH
- neurosekreční systémy fyziologie MeSH
- pohlavní hormony metabolismus MeSH
- předčasná puberta etiologie patofyziologie MeSH
- puberta fyziologie MeSH
- systém hypotalamus-hypofýza fyziologie MeSH
- Publikační typ
- přehledy MeSH
