Prenatal dihydrotestosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in sheep

The control of LH secretion in sheep is sexually differentiated. Males begi n to reduce their sensitivity to inhibitory steroid feedback, leading to a pubertal increase in tonic LH secretion by 10 weeks of age, but females rem ain hypersensitive until 30 weeks. Moreover, only females can respond to th e positive feedback action of estradiol to produce a preovulatory LH surge. Prenatal exposure of the female lamb to testosterone masculinizes tonic LH and abolishes the LH surge postnatally. However, the type of steroid invol ved is not known because testosterone can be converted to estradiol or dihy drotestosterone (DHT). This study tested the hypothesis that DHT, which can not be converted to an estrogen, masculinizes tonic LH without defeminizing the LH surge. Pregnant ewes were treated with DHT (800, 400, or 200 mg/wee k) during the critical period for sexual differentiation of gonadotropin se cretion (days 30-90; 145 days is term). To evaluate the time of the decreas e in responsiveness to steroid inhibition, a constant steroid feedback sign al was produced. At 4 weeks of age, androgenized females (800 mg, n = 5; 40 0 mg, n = 4; 200 mg, n = 5) and control males (n = 7) and females (n = 9) w ere gonadectomized and implanted with a SILASTIC brand estradiol capsule. T onic LH secretion in males began to increase at 6.7 +/- 0.5 weeks (mean +/- SEM). In DHT-treated females, the LH increase began at the same time (800 mg DHT, 10.7 +/- 3.9 weeks; 400 mg DHT, 9.9 +/- 5.9 weeks; 200 mg DHT, 7.1 +/- 4.9 weeks). This was several months earlier than in control females (29 .1 +/- 0.8 weeks; P < 0.05). After puberty, estradiol induced LH surges in 8 of 9 control females and 11 of 12 DHT-treated females, but not in any con trol males. These results lead to the hypothesis that in the sheep, distinc t requirements exist for differentiation of 2 types of reproductive hormone control systems, and that conversion of testosterone to an estrogen is not essential for both. Aromatization is necessary to prevent the surge contro l of GnRH from operating in the male, but nonaromatizable androgens differe ntiate the tonic control to permit high GnRH secretion earlier in life.