Influence of Gonadectomy and Replacement with Estradiol or Testosterone on Formation of 5α-Reduced Metabolites of Corticosterone by the Adrenal Gland of the Rat¹

Abstract

The effects of prepuberal gonadectomy on adrenal function were studied in both male and female rats. Steroid production was measured in vitro using either adrenal homogenates or slices. Adrenal tissue from castrated animals of either sex produced less steroid when determined by acid fluorescence or ultraviolet absorption. The effect was reversed after replacement with testosterone or estradiol. No difference due to castration was observed when steroid production was measured with blue tetrazolium. Corticosterone added in vitro to adrenal tissue from gonadectomized rats was converted to a fluorescence negative, ultraviolet negative, blue tetrazolium positive metabolite. This conversion was inhibited by gonadal hormone replacement in vivo. The metabolite was identified by Rf both before and after acetylation on several paper and thin layer chromatographic systems and also by infrared spectroscopy as 3β,5α-tetrahydrocorticosterone (compound R). Two additional compounds tentatively identified by chromatography alone were 3α,5α-tetrahydrocorticosterone and 5α-dihydrocorticosterone. Further studies showed that the decreased production of steroids by adrenal homogenates observed after ovariectomy was abolished by preincubation of the tissue as slices. Such preincubation concomitantly reduced the conversion of added corticosterone to compound R. The reaction involves 2 enzymes, 5α-reductase and 3-hydroxysteroid dehydrogenase. Activity of the latter is not increased after castration. The results demonstrate that gonadectomy enhances the capacity of the adrenal gland to convert corticosterone to compound R and other tetrahydro metabolites. The data are consistent with the hypothesis that adrenal 5α-reductase activity is increased after castration and is inhibited by replacement with testosterone or estradiol. These effects may represent a physiologic mechanism for regulation of adrenal steroid secretion.