Effects of Hypophysectomy and Administration of Cortisone or ACTH on Adrenal 5α-Reductase Activity and Steroid Production1

Preliminary studies in female rats demonstrated that adrenal 5α-reductase activity is inhibited by ACTH administration and stimulated by cortisone administration. Hypophysectomy in either sex results in enhanced activity of the enzyme in adrenal homogenates 48 hr after operation and markedly decreased recovery of corticosterone (Cpd. B) measured by acid fluorescence. Total production of corticosteroids measured by the blue tetrazolium reaction is only minimally affected. Replacement with ACTH reverses these changes, but is less effective in female rats. Acute loss of gonadal function may be excluded as the sole cause of the response to removal of the pituitary since gonadectomy is ineffective in the same time interval. Testosterone administered to hypophysectomized male rats inhibits adrenal reductase activity and increases the production of Cpd. B in vitro. Estradiol produces no change. Activity of the reductase increases progressively up to at least 96 hr after hypophysectomy. Cpd. B production varies inversely with reductase activity, i while adrenal glucose-6-phosphate dehydrogenase activity declines in the first 24 hr after hypophysectomy and remains essentially constant thereafter. Cortisone administration for 1 week stimulates adrenal reductase activity in both intact and mature-gonadectomized rats. Cpd. B production is correspondingly reduced. ACTH administration reverses these changes. No additional change in enzyme activity is observed when cortisone is administered to hypophysectomized rats. After withdrawal of cortisone, adrenal reductase activity falls to the control range within 11 days, whereas depressed Cpd. B production persists for at least 14 days. The results provide additional evidence for the participation of 5α-reductase in the modulation of adrenal cortical secretion and indicate that its activity is regulated by ACTH as well as estradiol and testosterone. (Endocrinology89: 432, 1971)