Regulation of Neurosteroid Biosynthesis by Neurotransmitters and Neuropeptides

摘要

It is now established that the brain has the capability of synthesizing biologically active steroids, termed neurosteroids, that participate in the regulation of various neurophysiological and behavioral processes. However, the neuronal mechanisms regulating the activity of neurosteroid-producing cells have not yet been elucidated. We recently found that, in the frog brain, three enzymes involved in steroid biosynthesis are actively expressed in hypothalamic neurons: 3 beta-hydroxysteroid dehydrogenase/A5-A4 isomerase (3beta-HSD), cytochrome P450 17a-hydroxylase/Cl7,20-lyase (P450Ci7) and hydroxysteroid sulfotransferase (HST). Concurrently, we showed that frog hypothalamic explants can convert tritiated pregnenolone ([3H]A5P) into various bioactive steroids, including 17-hydroxypregnenolone (17OH-A5P), progesterone (P), 17-hydroxyprogesterone (170H-P), dehydroepiandrosterone (DHEA), A5P sulfate (A5PS) and DHEA sulfate (DHEAS). The hypothalamic nuclei, where the 3p-HSD-, P45Oa7_ and HST- expressing neurons are located, receive afferent fibers containing a variety of neurotransmitters and neuropeptides. Here, we show that GABA, endozepines and neuropeptide Y (NPY) regulate neurosteroid biosynthesis.