PRENATAL ANDROGENS TIME NEUROENDOCRINE PUBERTY IN THE SHEEP - EFFECT OF TESTOSTERONE DOSE

In sheep, prenatal exposure to androgens during a critical period for sexual differentiation of the brain (30-90 days of gestation; 145 days is term) can advance the timing of puberty in females and prevent the preovulatory LH surge. The present study tests the hypothesis that in sheep, the timing of neuroendocrine sexual maturation is related to t he amount of prenatal steroid exposure. In addition, we determined if different steroid requirements exist for sexual differentiation of the tonic and surge modes of gonadotropin secretion. Testosterone was adm inistered weekly to three groups of pregnant ewes from days 30-90 of g estation at doses of 200, 80, or 32 mg/week. The resulting androgenize d female lambs together with control males and females (n = 5-7/group) were gonadectomized at 3 weeks of age, and gonadal steroids were repl aced with a SILASTIC brand estradiol filled capsule. LH concentrations were measured from biweekly blood samples. Sustained increases in cir culating LH were considered to reflect the initiation of neuroendocrin e puberty. In male lambs, LH secretion started to increase at 8.3 +/- 0.9 weeks of age (mean +/- SEM). The two highest doses of prenatal and rogen advanced the onset of neuroendocrine sexual maturation in female s. In the 200 mg androgenized females, the pubertal LH rise (10.2 +/- 2.0 weeks) began about the same time as in males. Tn the 80 mg treatme nt group, LH concentrations increased at 16.2 +/- 1.5 weeks, which was later than in males, but well before that in normal females (27.1 +/- 0.7 weeks. For females treated viith the lowest dose of androgen (32 mg), the pubertal LH increase (24.6 +/- 1.9 weeks) began about the sam e time as in normal females. To test the function of the LH surge syst em, LR was measured every 2 h for 60 h after an acute increase in circ ulating estradiol was produced by implanting additional estrogen capsu les. All control females produced a surge in response to acute estradi ol stimulation. LH surges did not occur in males, 200 mg androgenized females, or 80 mg androgenized females. Of six females from the 32 mg treatment group, two produced LH surges in response to the stimulatory feedback action of estradiol; me conclude that the greater the amount of prenatal testosterone, the earlier the initiation of the pubertal LH rise. Moreover, the finding that low doses of testosterone (32 mg/w eek) are capable of abolishing the LH surge without significantly adva ncing the timing of puberty supports our hypothesis that different ste roid requirements exist for sexual differentiation of tonic and surge modes of LH secretion.