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两栖动物中未结合型和硫酸化神经甾体合成的解剖学和生化证据。

Anatomical and biochemical evidence for the synthesis of unconjugated and sulfated neurosteroids in amphibians.

作者信息

Mensah-Nyagan A G, Beaujean D, Luu-The V, Pelletier G, Vaudry H

机构信息

European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, University of Rouen, 76821, Mont-Saint-Aignan, France.

出版信息

Brain Res Brain Res Rev. 2001 Nov;37(1-3):13-24. doi: 10.1016/s0165-0173(01)00110-2.

DOI:10.1016/s0165-0173(01)00110-2
PMID:11744071
Abstract

Various studies have shown that, in mammals, neurons and glial cells are capable of synthesizing bioactive steroids, or neurosteroids, which regulate the activity of the central nervous system (CNS). However, although steroid hormones are involved in the regulation of behavioral and neuroendocrine processes in amphibians, neurosteroid biosynthesis has never been studied in the CNS of non-mammalian vertebrates. Reviewed here are several data sets concerning the production of unconjugated and sulfated neurosteroids in amphibians. These data were obtained by investigating the immunohistochemical localization and activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and hydroxysteroid sulfotransferase (HST), in the frog brain. Numerous 3beta-HSD-immunoreactive neurons were detected in the anterior preoptic area, nucleus of the periventricular organ, posterior tuberculum, ventral and dorsal hypothalamic nuclei. 17beta-HSD-like immunoreactivity was found in ependymal gliocytes bordering the lateral ventricles of the telencephalon. Two populations of HST-immunoreactive neurons were localized in the anterior preoptic area and the dorsal magnocellular nucleus of the hypothalamus. High amounts of progesterone (PROG), 17-hydroxyprogesterone (17OH-PROG), testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) were measured in the frog brain by combining HPLC analysis of tissue extracts with radioimmunoassay detection. Incubation of telencephalic or hypothalamic explants with tritiated pregnenolone ([3H]PREG) yielded the synthesis of various metabolites including PROG, 17OH-PROG, DHEA and T. Incorporation of [35S]3'-phosphoadenosine 5'-phosphosulfate ([35S]PAPS) and [3H]PREG or [3H]DHEA into frog brain homogenates led to the formation of [3H,35S]pregnenolone sulfate ([3H,35S]PREGS) or [3H,35S]DHEAS, respectively. Altogether, these results demonstrate that the process of neurosteroid biosynthesis occurs in amphibians as previously seen in mammals.

摘要

多项研究表明,在哺乳动物中,神经元和神经胶质细胞能够合成生物活性类固醇,即神经甾体,其可调节中枢神经系统(CNS)的活性。然而,尽管类固醇激素参与两栖动物行为和神经内分泌过程的调节,但神经甾体生物合成从未在非哺乳动物脊椎动物的中枢神经系统中得到研究。本文综述了一些有关两栖动物中未结合和硫酸化神经甾体产生的数据集。这些数据是通过研究蛙脑中3β-羟基类固醇脱氢酶(3β-HSD)、17β-羟基类固醇脱氢酶(17β-HSD)和羟基类固醇硫酸转移酶(HST)的免疫组织化学定位和活性而获得的。在视前区前部、室周器官核、后结节、下丘脑腹侧和背侧核中检测到大量3β-HSD免疫反应性神经元。在端脑侧脑室周围的室管膜神经胶质细胞中发现了17β-HSD样免疫反应性。两群HST免疫反应性神经元定位于视前区前部和下丘脑背侧大细胞核。通过将组织提取物的高效液相色谱分析与放射免疫分析检测相结合,在蛙脑中检测到了大量的孕酮(PROG)、17-羟孕酮(17OH-PROG)、睾酮(T)和硫酸脱氢表雄酮(DHEAS)。用氚标记的孕烯醇酮([3H]PREG)孵育端脑或下丘脑外植体,可合成包括PROG、17OH-PROG、脱氢表雄酮(DHEA)和T在内的各种代谢产物。将[35S]3'-磷酸腺苷5'-磷酸硫酸酯([35S]PAPS)与[3H]PREG或[3H]DHEA掺入蛙脑匀浆中,分别导致形成[3H,35S]孕烯醇酮硫酸酯([3H,35S]PREGS)或[3H,35S]DHEAS。总之,这些结果表明,神经甾体生物合成过程在两栖动物中与在哺乳动物中一样存在。

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