PRENATAL TESTOSTERONE DIFFERENTIALLY MASCULINIZES TONIC AND SURGE MODES OF LUTEINIZING-HORMONE SECRETION IN THE DEVELOPING SHEEP

In sheep, prenatal exposure to androgens during a critical period for sexual differentiation can masculinize tonic luteinizing hormone (LH) secretion and defeminize the LH surge. The present study investigated the possible independent control of these two modes of LH secretion, as revealed by their developmental history. Specifically, we tested the hypothesis that separate critical periods exist for androgenization of tonic and surge LH secretion. Pregnant ewes were treated weekly with testosterone cypionate (200 mg in oil). As a control and to induce robust masculinization of reproductive neuroendocrine function, one group of females received testosterone from day 30 to 86 of gestation (LONG group). To determine if masculinization of tonic LH secretion develops separately from that of the LH surge, two additional groups were treated from day 30 to 51 (EARLY group) or 65-86 (LATE group). At birth, the external genitalia of the LONG- and EARLY-treated females were masculinized; those of the LATE-treated group were normal. At 2 weeks of age, all androgenized females, together with normal males and females (n = 8 each), were gonadectomized and steroids replaced using an estradiol-filled Silastic capsule. First, to determine the timing of the pubertal decrease in steroid sensitivity, circulating LH was monitored twice weekly. Second, to test the function of the LH surge system, LH was measured every 1-2 h for 60 h after an acute increase in estradiol at 9 months of age. With regard to tonic LH secretion, in control males and LONG-treated females, a sustained increase in tonic LH in the presence of constant steroid feedback occurred at 7.1 +/- 0.3 and 10.9 +/- 1.7 weeks of age, respectively (mean +/- SE). In control females, tonic LH increased at 27.1 +/- 0.8 weeks. Despite the differences in their genitalia, EARLY and LATE testosterone treatment produced intermediate effects: LH secretion increased at 19.3 +/- 1.2 and 20.4 +/- 0.8 weeks, respectively. In response to acute estradiol stimulation, all control females produced a surge of LH that peaked 18.4 rt 0.6 h after steroid treatment. For the control males and LONG-treated females, LH concentrations were not sustained above unsuppressed pretreatment levels throughout the 60-hour sampling period. All but 4 of the 18 EARLY- and LATE-treated females responded to estradiol stimulation with a surge of LH that peaked at 29.8 +/- 1.6 and 31.8 +/- 1.3 h, significantly later than that of control females. These data indicate that it is possible to advance the pubertal increase in tonic LH secretion without preventing the LH surge, thereby suggesting that tonic and surge LH secretion can be differentially masculinized by prenatal testosterone.