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Prenatal Dihydrotestosterone Differentially Masculinizes Tonic and Surge Modes of Luteinizing Hormone Secretion in Sheep¹

Reproductive Sciences Program and Department of Biology (K.S.M., D.L.F.), and Department of Obstetrics and Gynecology and Biology (D.L.F.), University of Michigan, Ann Arbor, Michigan 48109-0404; and the Departments of Obstetrics and Gynecology and Molecular, Cellular, and Developmental Biology, Yale University (R.I.W.), New Haven, Connecticut 06520-8063

Address all correspondence and requests for reprints to: Dr. Douglas L. Foster, Room 1101, 300 North Ingalls Building, Ann Arbor, Michigan 48109-0404. E-mail: dlfoster{at}umich.edu

The control of LH secretion in sheep is sexually differentiated. Males begin to reduce their sensitivity to inhibitory steroid feedback, leading to a pubertal increase in tonic LH secretion by 10 weeks of age, but females remain hypersensitive until 30 weeks. Moreover, only females can respond to the 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 involved is not known because testosterone can be converted to estradiol or dihydrotestosterone (DHT). This study tested the hypothesis that DHT, which cannot be converted to an estrogen, masculinizes tonic LH without defeminizing the LH surge. Pregnant ewes were treated with DHT (800, 400, or 200 mg/week) during the critical period for sexual differentiation of gonadotropin secretion (days 30–90; 145 days is term). To evaluate the time of the decrease in responsiveness to steroid inhibition, a constant steroid feedback signal was produced. At 4 weeks of age, androgenized females (800 mg, n = 5; 400 mg, n = 4; 200 mg, n = 5) and control males (n = 7) and females (n = 9) were gonadectomized and implanted with a SILASTIC brand estradiol capsule. Tonic 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 control males. These results lead to the hypothesis that in the sheep, distinct 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 control of GnRH from operating in the male, but nonaromatizable androgens differentiate the tonic control to permit high GnRH secretion earlier in life.

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