The Regulation System of Brain Aromatase Activity

Abstract

Recently, some studies have found the greatest aromatase activity in brain areas associated with sexual differention and sexual behavior, namely the hypothalamic and limbic structures. We studied the regulation of aromatase activity in the hypothalamic area of male rats, using a sensitive in vitro assay which measures the amount of 3H2O formed by tissue homogenates during the conversion of [1 beta-3H] androstenedione to estrogen. After castration, hypothalamic aromatase activity was significantly decreased (P less than 0.01), and seminal vesicle (SV) and prostate (PR) weights were also significantly decreased (P less than 0.01). Castrated male rats were given testosterone (T), 5 alpha-dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha, 17 beta-diol (A3 alpha), 5 alpha-androstane-3 beta and 17 beta-diol(A3 beta) in various doses (200-1000 micrograms/day) for 10 days, and were given 600 micrograms/day T, DHT, A3 alpha and A3 beta for various durations (1-10 days). We found that T, DHT and A3 alpha but not A3 beta reversed the effects of castration on the hypothalamic aromatase activity. The order of this reversible effect of androgens was as follows: T greater than or equal to DHT greater than A3 alpha. T, DHT, A3 alpha and A3 beta increased SV and PR weights, and the order of this effect was as follows: DHT greater than T greater than A3 alpha much greater than A3 beta. We administered the antiandrogen (flutamide) to intact male rats (8 mg/day for 6 days). Flutamide decreased hypothalamic aromatase activity at the same level as that of castrated rats. Likewise, administration of both flutamide and T to castrated rats blocked the T-induced increase in hypothalamic aromatase activity and accessory sexual organ weight. From these results, we suggest that T, DHT and A3 alpha regulated hypothalamic aromatase activity, that T was the most effective of the androgens, and that was different from peripheral androgen target organs.