Some Studies on the Effect of Androgens on Adrenal Cortical Function of Rats

Abstract

The effect of ACTH upon the inhibition of corticosteroidogenesis produced by treating rats with several synthetic adrogens has been evaluated. In experiments lasting about 2 weeks in which the simultaneous treatment with ACTH prevented the fall in adrenal weight due to the androgen therapy, corticosteroidogenesis measured in adrenal homogenates was still greatly reduced. Associated with the reduced production of corticosterone from progesterone there was a marked fall in the level of adrenal mitochondrial cytochrome P-450. The fall in cytochrome P-450 was not prevented by simultaneous treatment with ACTH. Treatment of rats with all 3 androgens, 17a-methylandrostenediol, 17a-methyltestosterone and 11/3-hydroxy-17«-methyltestosterone, brought about the decrease in cytochrome P-450 levels, whereas when metyrapone, a nonsteroidal competitive inhibitor of steroid 11/3-hydroxylase, was given to rats for 6 weeks no change occurred in the level of adrenal mitochondrial cytochrome P-450. These data suggest that this property of the androgens is not necessarily related to their potential as inhibitors of steroid hydroxylases. {Endocrinology 86: 1085, 1970)

The effects of flutamide on the neonatal rat hypothalamic–pituitary–adrenal and gonadal axes in response to hypoxia

“…Although the adult rat adrenal does not express CYP17 and cannot synthesize appreciable androgens (Gallo-Payet & Battista, 2014), the neonatal rat adrenal may have the capacity to synthesize androgens that could be a critical local factor in the development of normal adrenal function (Pignatelli, Xiao, Gouveia, Ferreira, & Vinson, 2006;Zhou, Kang, Chen, Han, & Ma, 2015). Furthermore, the neonatal adrenal may express the AR making it susceptible to circulating testosterone from the gonads (Brownie, Colby, Gallant, & Skelton, 1970;Calandra et al, 1978;Rifka, Cutler, Sauer, & Loriaux, 1978).…”

Biological Aspects of Cytochrome P450 and Associated Hydroxylation Reactions

“…However, the cytochrome P450 levels and steroid hydroxylation capacities can be restored on adminis tration of ACTH [76,118]. Administration of several synthetic androgens to female rats resulted in a marked fall in the level of adrenal mitochondrial cytochrome P450 and the rate of corticosteroidogenesis, even when ACTH was used to maintain the weight of the adrenal [11], These observations exemplify the difficulties inherent in determining the 'normal' content and function of cytochrome P450-dependent steroid hydroxylases in endocrine tissues and since these questions have been extensively discussed by others [see 9,25,35,53,90,91,126,129,145] they will not be elaborated on here.…”

Expression of adrenal cytochromes P-450 in testosterone-induced hypertension.

“…3 -5 The major defect in androgen-treated animals is impaired 11/J-hydroxylation of 11-deoxycorticosterone (DOC) to corticosterone. 4 - 5 This results in the accumulation of DOC, a mineralocorticoid that is known to produce hypertension in rats. 6 -7 The mechanism for this defect in corticosteroidogenesis is unclear.…”