Sexual differentiation of the mechanism controlling pulsatile secretion of luteinizing hormone contributes to sexual differences in the timing of puberty in sheep.

Sexual differences in the regulation of tonic luteinizing hormone (LH) secretion were examined in immature female and male sheep (eight each, including six pairs of female/male twins). After gonadectomy of lambs at 2 weeks of age, Silastic capsules filled with estradiol, a primary central feedback steroid in both females and males, were implanted every 3 weeks for 3 days, and then removed, so that the pattern of LH secretion could be repeatedly determined in the same individuals both with and without steroid feedback. Implanted capsules yielded circulating steroid levels of 2-5 pg/ml. Circulating LH concentrations were determined by radioimmunoassay in blood samples collected at 12-min intervals for 4 h immediately before estradiol was implanted, and again, immediately before it was removed 3 days later. In male lambs, a decrease in responsiveness of the hypothalamic-pituitary axis to inhibition by estradiol began at 8-11 weeks, as evidenced by the progressive increase in mean LH concentrations and frequency of LH pulses. This correlated temporally with the onset of spermatogenesis in intact male controls (n = 8). In females, a similar decrease in responsiveness did not occur until 26-29 weeks of age, corresponding to the onset of ovulatory cycles in intact female controls (n = 6). In the absence of estradiol implants, LH pulse frequencies were higher in male lambs than in female lambs between 5 and 35 weeks of age. There was no further increase in LH pulse frequency in the absence of the gonads in either sex during the pubertal period. These findings suggest that the mechanism regulating tonic LH secretion in developing lambs is sexually differentiated in its responsiveness to inhibition by estradiol. This differentiation also occurs at a more fundamental steroid-independent level, but any causal relationship between the higher steroid-independent LH pulse frequency and the lower responsiveness to estradiol negative feedback in males is not evident. We hypothesize that these sexual differences in the regulation of tonic LH underlie the difference in the timing of puberty in male and female lambs.