SEX-DIFFERENCES IN ANDROGEN RESPONSIVENESS IN THE RAT-BRAIN - REGIONAL DIFFERENCES IN THE INDUCTION OF AROMATASE-ACTIVITY

The transformation of testosterone (T) to estrogens in brain tissue by cytochrome P-450 aromatase is required for the expression of sexual b ehaviors in adult male rats. Androgens regulate aromatase activity in the medial preoptic nucleus (MPN), as well as in a reciprocally connec ted group of forebrain nuclei involved in the regulation of male sexua l behaviors. The levels of aromatase in these nuclei are generally gre ater in males than in females due to sex differences in circulating an drogen levels. However, the mechanism of enzyme induction also appears to be sexually dimorphic. The current experiments were undertaken: (1 ) to characterize and compare the kinetic properties of aromatase in m ale and female rats and (2) to study sex differences in the dose-respo nse relationship between the administered doses of T and the induction of aromatase in microdissected brain regions. Saturation analysis of aromatase activity in the MPN, bed nucleus of the stria terminalis (BN ST), periventricular preoptic area (PVPOA), anterior hypothalamus (AH) , and ventromedial hypothalamic nucleus (VMN) indicates that the great er aromatase activity observed in intact males reflects a sex differen ce in the maximal enzyme velocity, and not a sex difference in the app arent affinity of enzyme for substrate (Michaelis constant). The dose- response study of aromatase induction in the BNST, PVPOA, and VMN indi cated a sex difference in aromatase activity over a range of circulati ng T levels varying from 0.3 to 35 ng/ml. No sex difference in inducib le aromatase activity in AH was observed at any dose of T. The results of this study clearly demonstrate a sexually dimorphic effect of andr ogen action in the rat brain. Since T both regulates and is the substr ate for aromatase in the brain, this sexual dimorphism is potentially an important limitation to the action of T in females and may relate t o the enhanced expression of T-stimulated copulatory behavior in males compared to females.