Age- and region-specific expressions of the messenger RNAs encoding for steroidogenic enzymes P450scc, P450c17 and 3β-HSD in the postnatal rat brain

Abstract

Neurosteroids are now known to be synthesized de novo in the nervous system through mechanisms at least partly independent of peripheral steroidogenic glands. In mammals, the presence of the cholesterol side-chain cleavage enzyme (cytochrome P450scc) and the enzyme 3β-hydroxysteroid dehydrogenase/Δ 5-Δ 4-isomerase (3β-HSD) has been well established in the brain, whereas limited information has been available on the enzyme 17α-hydroxylase/c17, 20-lyase (cytochrome P450c17), which converts pregnenolone to dehydroepiandrosterone, one of the most abundant neurosteroids. In addition, little is known regarding developmental changes in these steroidogenic enzymes during postnatal 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 3β-HSD, in the rat brain at different postnatal ages using RT-PCR analysis. The expression of P450scc mRNA was found throughout the brain at the same level, while the 3β-HSD mRNA expression was higher in the cerebellum and cerebrum than in other brain regions. The P450c17 mRNA was highly expressed in the mesencephalon. On the other hand, higher expressions of the cerebellar and cerebral 3β-HSD mRNAs were observed only in neonatal life. In contrast, the expression of P450scc mRNA was relatively constant during neonatal life and in adulthood. A similar constant expression of the P450c17 mRNA was evident in the mesencephalon. Serial Southern hybridization in this study confirmed the specific mRNA expression corresponding to each enzyme. These results suggest that in the postnatal rat the expression of 3β-HSD or P450c17 mRNA may be age- or region-dependent, unlike the P450scc mRNA expression.