Evidence for changes in sensitivity to testosterone negative feedback on gonadotropin release during sexual development in the male rat

Male rats were castrated at different ages and injected sc once daily for 2 days with either oil or various doses of testosterone propionate (TP). Castration elevated serum gonadotropins at all ages studied from day 15 to clay 88, but the response was maximal for LH at 58 days and minimal at 15 days. The elevation of FSH was minimal at 88 days but similar at other ages. Whereas 10 μg/100 g body wt of TP were sufficient to prevent the rise in serum FSH and LH which occurred 2 days after castration in 15-day-old rats and 10 M-g were still effective in 28-day-old animals, the suppressibility of serum gonadotropins decreased with age and by 58 days the 10 μg/100 g body wt dose was no longer effective. Higher doses of TP suppressed the increase in serum LH and FSH at all ages studied. The results suggest that the sensitivity of the hypothalamic pituitary unit to the negative feedback of testosterone declines during sexual development and that this change, which is especially noticeable at the time of puberty, may be responsible for maintenance of gonadotropin release in the face of rising testosterone levels and play a role in the induction of puberty. In another experiment, the initiation of TP replacement therapy was delayed for 5 days. In contrast to the results when replacement was initiated immediately, differential sensitivity of LH to TP at 20 and 60 days of age could not be demonstrated under these conditions. Surprisingly, in this situation, the 25 μg dose was able to prevent partially the post-castration rise in FSH at 60 days, whereas both 10 and 25 μg doses were ineffective at 20 days. These findings suggest that removal of the gonads in the immature male rat elevates the setpoint of the feedback system, setting it at the higher level of androgens encountered in the mature animal.