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 3/3,5o:-tetrahydrocorticosterone (compound R). Two additional compounds tentatively identified by chromatography alone were 3a,5a-tetrahydrocorticosterone and 5a-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, 5a-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 5a-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. {Endo-crinology 87: 1257{Endo-crinology 87: , 1970 /CONSIDERABLE evidence is available \jk to indicate that pituitary-adrenal function is influenced by the gonadal hormones (2). However, physiologic roles for estradiol and testosterone in the regulation of adrenal function have been difficult to define. The available data seem contradictory since both stimulatory and inhibitory effects have been described for both hormones. Much of the disagreement can be related to wide variations in experimental designs used in different laboratories. For example, dose is a critical factor. The effects of estradiol and testosterone appear to

Effects of Melatonin and an Aqueous Pineal Extract on Adrenal Secretion of Reduced Steroid Metabolites in Female Rats

“…Adrenal tissue was incubated under air at 37 °C with 25 pg B in a final volume of 0.25 ml for 60 min. Details of reaction mixture and other procedures have been presented [Ogle and K itay, 1974], The rate of disappearance of added steroid was deter mined by the loss of fluorescence shown previously to coincide with the formation of 5^-reduced metabolites [Kitay et at., 1970[Kitay et at., , 1971a. Adrenal slices were incubated at 37°C in Krebs-Ringer-bicarbonate medium (KRB) under an atmosphere of 95% 0 2-5% C 0 2.…”

Pituitary-Adrenal Function in Pseudopregnant Rats

“…Adrenal slices and homogenates were prepared and incubated as previously reported [10], Corticosterone production in the incubates was measured by acid fluorescence [8]. Total steroid production was evaluated by the blue tetrazolium reaction [15], which measures all steroids with an \-ketol side chain.…”

“…Total steroid production was evaluated by the blue tetrazolium reaction [15], which measures all steroids with an \-ketol side chain. Adrenal 5x-reductase activity was assayed in homogenates [10]. Adrenal venous blood was col lected for 15 min following induction of anesthesia with ether [I I].…”

In vitro effects of oestrogen on 5α reduction of testosterone in hormone-dependent rat mammary carcinomata

“…In vitro addition of oestradiol reduces tumour synthesis of 5ac-reduced metabolites from testosterone, particularly 5ac androstanediol. Although this is the first report that oestrogen may affect the production of 5a-reduced steroids by mammary cancers, it is well documented that 5ac-reduction may be hormonally controlled in other tissues such as liver (Schriefers, 1967), adrenal cortex (Kitay, Coyne and Swygert, 1970) and prostate (Farnsworth, 1972). In common with the results presented in this study for mammary tissue, oestradiol inhibits 5ac-reduction in both adrenal cortex and prostate.…”