Progesterone-transforming enzyme activity in the hypothalamus of the male rat

The aim of the present study was to assess the activities of the progestero ne (Pr) transforming enzyme systems 3 alpha-oxidoreductase (3 alpha-OR), 5 alpha-reductase (5 alpha-R) and 20 alpha-oxidoreductase (20 alpha-OR) in th e hypothalamus of the male rat, at different stages of sexual maturation an d following castration and adrenalectomy. Special attention was paid to tra nsformation to 3 alpha-reduced compounds previously shown to inhibit FSH sy nthesis and secretion. Homogenates of hypothalamic tissue were incubated wi th C-14-progesterone. Pr-metabolites were isolated, identified by gas chrom atography/mass-spectrometry (GC/MS) and measured by liquid scintillation co unting (LSC). In adult rats a ratio of 6:2.5:1 for 5 alpha-R:3 alpha-OR:20 alpha-OR enzym e-activities was found. The hypothalamic 5 alpha-R and particularly 3 alpha -OR activities were considerably higher before puberty (10-20 day old rats) than in adulthood. Adrenalectomy in adult rats resulted in an increased ac tivity of the three enzyme systems. No significant changes were seen follow ing castration. Among the isolated metabolites, 3 alpha-hydroxy-pregn-4-en-20-one (3 alpha- Pr) and 3 alpha-hydroxy-5 alpha-pregnane-20-one (5 alpha,3 alpha-Pr) were i dentified. Conversion to both these neurosteroids was considerably higher d uring prepuberty than in adulthood. The finding that before puberty the hyp othalamus has a markedly increased capacity to convert Pr to 3 alpha-reduce d compounds, such as 3 alpha-Pr, known to effectively inhibit FSH release, warrants further research into the mechanisms regulating the hypothalamic f ormation of biologically active Pr derivatives and their role in the regula tion of gonadotropin secretion. (C) 1999 Elsevier Science Ltd. All rights r eserved.