STEROID-METABOLISM IN THE MAMMALIAN BRAIN - 5ALPHA-REDUCTION AND AROMATIZATION

Several steroid molecules, including androgens, estrogens, progestagen s, and corticostereroids, are able to modulate the brain development a nd functions. These compounds are not always active in their own natur al molecular configuration but they often need to be transformed at th e level of their target cells into 'active metabolites'. The two major metabolic pathways that transform steroids in the brain are: the 5alp ha-reductase-3alpha-hydroxy-steroid dehydrogenase and the aromatase pa thways. Both are present in the brain and probably exert specific role s in the mechanism of action of hormonal steroids. In this article we briefly review some important findings achieved in our own and in othe r laboratories concerning the cellular and subcellular brain distribut ion, development, regulation, cloning, and molecular characterization of the involved enzymes. In particular, the recent identification of t wo isoforms of the 5alpha-reductase, the type 1 and type 2, possessing different structural, biochemical, and distribution characteristics h as attracted a considerable attention. The few data available on their brain distribution have been carefully considered. Finally, we have t ried to focus on the role of the steroid metabolites in the brain, bot h when they interact with genomic and with membrane receptors. In part icular, some unpublished observations on the effects of two 5alpha-red uctase inhibitors on progesterone-induced anesthesia, a phenomenon med iated through the GABA(A) receptor, are presented. (C) 1997 Elsevier S cience Inc.