AGE-SPECIFIC AND REGION-SPECIFIC EXPRESSIONS OF THE MESSENGER-RNA ENCODING FOR STEROIDOGENIC ENZYMES P450SCC, P450C17 AND 3-BETA-HSD IN THEPOSTNATAL RAT-BRAIN

Neurosteroids are now known to be synthesized de novo in the nervous s ystem through mechanisms at least partly independent of peripheral ste roidogenic glands. In mammals, the presence of the cholesterol side-ch ain cleavage enzyme (cytochrome P450scc) and the enzyme 3 beta-hydroxy steroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3 beta-HSD) has bee n well established in the brain, whereas limited information has been available on the enzyme 17 alpha-hydroxylase/c17, 20-lyase (cytochrome P450c17), which converts pregnenolone to dehydroepiandrosterone, one of the most abundant neurosteroids. In addition, little is known regar ding developmental changes in these steroidogenic enzymes during postn atal life. Thus, the pathway of neurosteroid formation in the brain is still incomplete. Therefore, we examined expressions of the messenger RNAs (mRNAs) encoding for three key enzymes, P450scc, P450c17 and 3 b eta-HSD, in the rat brain at different postnatal ages using RT-PCR ana lysis. The expression of P450scc mRNA was found throughout the brain a t the same level, while the 3 beta-HSD mRNA expression was higher in t he cerebellum and cerebrum than in other brain regions. The P450c17 mR NA was highly expressed in the mesencephalon. On the other hand, highe r expressions of the cerebellar and cerebral 3 beta-HSD mRNAs were obs erved only in neonatal life. In contrast, the expression of P450scc mR NA was relatively constant during neonatal life and in adulthood. A si milar constant expression of the P450c17 mRNA was evident in the mesen cephalon. Serial Southern hybridization in this study confirmed the sp ecific mRNA expression corresponding to each enzyme. These results sug gest that in the postnatal rat the expression of 3 beta-HSD or P450c17 mRNA may be age- or region-dependent, unlike the P450scc mRNA express ion. (C) 1998 Elsevier Science B.V. All rights reserved.