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

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.