SEX-DIFFERENCES IN ANDROGEN-REGULATED CYTOCHROME-P450 AROMATASE MESSENGER-RNA IN THE RAT-BRAIN

The conversion of testosterone to estradiol by cytochrome P450 aromata se (P450(AROM)) in the medial preoptic area is required for full expre ssion of male sexual behavior in rats, Preoptic P450(AROM) activity is stimulated by androgens through an androgen-receptor mediated mechani sm that regulates P450(AROM) gene expression. The mechanism of enzyme induction appears to be sexually dimorphic in several species leading to greater testosterone-stimulated P450(AROM) activity in males than i n females, The present study was designed to determine whether the sex difference in androgen-regulated P450(AROM) activity is manifested at the levels of mRNA expression. We compared the concentrations of P450 (AROM) mRNA and enzyme activity between five different treatment group s: intact males, castrated males (CX), ovariectomized females (OVX), C X males treated with dihydrotestosterone (CX + DHT), and OVX females t reated with DHT (OVX + DHT). We found that unstimulated levels of P450 (AROM) mRNA and enzyme activity in both the preoptic area and medial b asal hypothalamus were similar in the CX and OVX groups. However, when treated with equivalent doses of DHT, the levels of P450(AROM) mRNA a nd enzyme activity in both brain regions were significantly higher in males than in females (i.e., CX + DHT group > OVX + DHT group). These results demonstrate that sex differences in the regulation of P450(ARO M) in brain are exerted pretranslationally by androgen and suggest tha t gender differences in androgen responsiveness play an important role in regulating gene expression in the adult rat brain.