RESUMEN
The aim of the present study was to assess the progesterone (Pr) transforming 5 alpha-reductase (5 alpha-R) and 3 alpha-oxidoreductase (3 alpha-OR) activities in the hypothalamus of the male rat as a function of age and following castration and/or adrenalectomy performed at the sixth day of life. The hypothalamic activity of these enzymes was estimated from the sum of the 5 alpha- or 3 alpha-reduced metabolites produced from 14C-labeled Pr incubated "in vitro" with hypothalamic tissue. Plasma levels of testosterone (T), progesterone (Pr), estrone (E1), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured simultaneously. Special attention was paid to the GC/MS analysis of the endogenous content of the hypothalamic Pr-metabolites 3 alpha-hydroxy-pregn-4-en-20-one (3 alpha-Pr), 5 alpha-pregnane-3,20-dione (5 alpha-Pr) and 3 alpha-hydroxy-5 alpha-pregnan-20-one (5 alpha,3 alpha-Pr). The high 5 alpha-R and 3 alpha-OR activities estimated in the hypothalamus of prepubertal rats are not related to the action of gonadal or adrenal steroids. Substantial and comparable endogenous 3 alpha- and/or 5 alpha-Pr-metabolites were found in hypothalami from both prepubertal and mature rats. The results of the present study do not provide evidence for a contributory role of the 3 alpha-hydroxylated Pr derivative to the regulation of gonadotropin secretion in the male rat.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Hipotálamo/enzimología , Oxidorreductasas/metabolismo , Progesterona/metabolismo , Adrenalectomía , Envejecimiento/fisiología , Animales , Radioisótopos de Carbono/metabolismo , Castración , Inhibidores Enzimáticos/farmacología , Estrona/sangre , Finasterida/farmacología , Hormona Folículo Estimulante/sangre , Hipotálamo/efectos de los fármacos , Hormona Luteinizante/sangre , Masculino , Progesterona/sangre , Ratas , Ratas Wistar , Testosterona/sangreRESUMEN
The aim of the present study was to assess the activities of the progesterone (Pr) transforming enzyme systems 3alpha-oxidoreductase (3alpha-OR), 5alpha-reductase (5alpha-R) and 20alpha-oxidoreductase (20alpha-OR) in the hypothalamus of the male rat, at different stages of sexual maturation and following castration and adrenalectomy. Special attention was paid to transformation to 3alpha-reduced compounds previously shown to inhibit FSH synthesis and secretion. Homogenates of hypothalamic tissue were incubated with 14C-progesterone. Pr-metabolites were isolated, identified by gas chromatography/mass-spectrometry (GC/MS) and measured by liquid scintillation counting (LSC). In adult rats a ratio of 6:2.5:1 for 5alpha-R:3alpha-OR:20alpha-OR enzyme- activities was found. The hypothalamic 5alpha-R and particularly 3alpha-OR activities were considerably higher before puberty (10-20 day old rats) than in adulthood. Adrenalectomy in adult rats resulted in an increased activity of the three enzyme systems. No significant changes were seen following castration. Among the isolated metabolites, 3alpha-hydroxy-pregn-4-en-20-one (3alpha-Pr) and 3alpha-hydroxy-5alpha-pregnane-20-one (5alpha,3alpha-Pr) were identified. Conversion to both these neurosteroids was considerably higher during prepuberty than in adulthood. The finding that before puberty the hypothalamus has a markedly increased capacity to convert Pr to 3alpha-reduced compounds, such as 3alpha-Pr, known to effectively inhibit FSH release, warrants further research into the mechanisms regulating the hypothalamic formation of biologically active Pr derivatives and their role in the regulation of gonadotropin secretion.