PRENATAL TESTOSTERONE DIFFERENTIATES BRAIN-REGIONS CONTROLLING GONADOTROPIN-RELEASE IN GUINEA-PIGS

Sexual differentiation of behavior and gonadotropin release in short-g estation mammalian species is affected by perinatal testosterone (T). Differentiation of dimorphic behaviors in two long-gestation species ( guinea pigs and rhesus macaques) depends upon prenatal androgen exposu re. The brain areas mediating gonadotropin release are not sexually di fferentiated in nonhuman primates, but similar information is not avai lable for the guinea pig. To obtain new information on this subject, w e treated pregnant guinea pig with testosterone propionate (TP; 2.5, 5 , or 10 mg/day) or vehicle (control) on Days 30-39 of gestation and 1. 0 mg/day of TP on Days 40-55 of gestation. The length of gestation in this strain (Topeka) ranges from 66 to 73 days. We evaluated permanent treatment effects on gonadotropin release by challenging adult guinea pigs with 10 mu g estradiol benzoate (EB, s.c.) 2 wk after gonadectom y. Serial serum samples were analyzed for LH by RIA. Control females ( 70.6%) released LH in surge quantities 40.1 +/- 0.7 h (mean +/- SEM, n = 24) after EB treatment. Prenatal T treatment in utero significantly decreased the number of EB-induced LH surges observed in adult female s (0 of 5, 2.5 mg TP; 0 of 10, 5 mg TP; 0 of 7, 10 mg TP). No LH surge s were induced by EB in any of the males. The postgonadectomy LH rise was 50 and 75% lower (p < 0.01) in females treated with 5 and 10 mg TP , respectively, than in other groups. Four days after the EB challenge , animals were infused with a bolus of GnRH (1 mu g/kg BW), and serial blood samples were taken. All groups showed a 5-fold increase of LH i n serum 15 min after GnRH treatment. In addition, we treated five preg nant females with 10 mg of dihydrotestosterone propionate (DHTP) for 1 0 days and with 1 mg thereafter as described for TP. The offspring of four of these pregnancies were stillborn, and the fifth pregnancy resu lted in abortion. These data demonstrate that prenatal androgen in the guinea pig differentiates cyclic centers controlling gonadotropin rel ease in the brain without affecting gonadotroph sensitivity. Even thou gh the guinea pig is a long-gestation species in which sexual differen tiation takes place before birth, the actions of androgens on the deve lopment of cyclic centers that control gonadotropin release are simila r to those reported for short-gestation rodents such as the rat, and d iffer from the actions of androgens as observed in nonhuman primates.