Prenatal testosterone differentiates brain regions controlling gonadotropin release in guinea pigs

Sexual differentiation of behavior and gonadotropin release in short-gestation 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 exposure. The brain areas mediating gonadotropin release are not sexually differentiated in nonhuman primates, but similar information is not available for the guinea pig. To obtain new information on this subject, we treated pregnant guinea pigs 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 micrograms estradiol benzoate (EB, s.c.) 2 wk after gonadectomy. 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 females (0 of 5, 2.5 mg TP; 0 of 10, 5 mg TP; 0 of 7, 10 mg TP). No LH surges 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 microgram/kg BW), and serial blood samples were taken.(ABSTRACT TRUNCATED AT 250 WORDS)