Androgens regulate brain aromatase activity in adult male rats through a receptor mechanism

Charles E. Roselli, John A. Resko

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

We studied the regulation of aromatase activity in the hypothalamus-preoptic area (HPOA) of adult male rats using a sensitive in vitro assay which measures the amount of 3H2O formed by tissue homogenates during the conversion of [1β-3H]androstenedione to estrone. After castration, HPOA aromatase activity was decreased by 60% (P < 0.05), seminal vesicle (SV) and ventral prostate (VP) weights were significantly decreased (P < 0.05), and serum LH levels were elevated. We found that testosterone (T) or 5α-dihydrotestosterone (DHT) administered in Silastic capsules for 7 days reversed the effects of castration. Testosterone and DHT stimulated HPOA aromatase activity 133% and 92%, respectively (P < 0.05). Both steroids significantly increased SV and VP wet weights and suppressed serum levels of LH (P < 0.05). Administration of either estradiol or progesterone did not reverse the effect of castration on HPOA aromatase activity or any other parameter measured. To determine the involvement of androgen receptors in the mechanism by which androgens affect brain aromatase, we administered the nonsteroidal antiandrogen flutamide to intact male rats (15 mg/day for 7 days). There was 42% less HPOA aromatase activity in treated rats than in oil-injected controls (P < 0.05). Flutamide significantly decreased SV and VP wet weights, while serum LH levels were enhanced (P < 0.05). Likewise, administration of flutamide to T-implanted castrated males blocked the T-induced increase in HPOA aromatase activity and accessory sexual organ wet weights, and prevented the T-induced suppression of serum LH. Flutamide given alone to castrated rats had no effect. Since both T and DHT stimulated HPOA aromatase activity and since the effects of T are blocked by the concomitant administration of the antiandrogen flutamide, we concluded that the control of HPOA aromatase activity by androgens is receptor mediated.

Original languageEnglish (US)
Pages (from-to)2183-2189
Number of pages7
JournalEndocrinology
Volume114
Issue number6
DOIs
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Endocrinology

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