Inhibition of estrogen-induced sexual receptivity by androgens: Role of the androgen receptor

Both naturally occurring and synthetic androgens have been shown to inhibit estrogen-induced sexual receptivity when administered to ovariectomized (OVX) rats. The mechanisms by which androgens exert these effects, however, remain unclear. Experiments were conducted to determine the role of the androgen receptor in the inhibition of estrogen-induced sexual receptivity in OVX rats by using flutamide, an androgen receptor antagonist. In each experiment, OVX Long-Evans rats received 6 consecutive days of estradiol benzoate (EB; 2.0 mu g/day) followed by 15 days of EB concurrent with flutamide (10.0 mg/kg; twice daily) or the vehicle and one of the following androgens or the vehicle: dihydrotestosterone propionate (7.5 mg/kg), 3 alpha-androstanediol (3.75 mg/kg), 17 alpha-methyltestosterone (7.5 mg/kg), stanozolol (7.5 mg/kg), or nandrolone decanoate (7.5 mg/kg). On Day 15, all female rats received progesterone (P; 1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of androgen/flutamide treatment. Each androgen inhibited sexual receptivity as expected, and concurrent treatment with flutamide reversed the inhibitory effects of all androgens on sexual receptivity on all test days. High levels of sexual receptivity were displayed in response to P on Day 15, regardless of experimental treatment. These results suggest that naturally occurring and synthetic androgens act at the androgen receptor to inhibit estrogen-induced sexual receptivity in OVX rats. (C) 1998 Academic Press.