Evidence that desensitization to the negative estrogen feedback is a prepubertal and not a postpubertal event in female rats

Female rats were ovariectomized at 31 days of age, on the day of proestrus, or on the day of the first vaginal estrus if corpora lutea were seen in the ovaries. Immediately after castration, estradiol-17 beta (E2) or oil was administered via s.c. silastics capsules, or a 1:240 mixture of estradiol benzoate (EB) and cholesterol or cholesterol alone was unilaterally implanted into the hypothalamic ventromedial-arcuate region. Forty-eight hours after surgery the rats were decapitated and the serum concentrations of LH and FSH estimated. In rats implanted s.c. with E2 in anestrus, proestrus or estrus, estrogen treatment reduced the circulating LH level to 9.4; 60.4 and 33.6% and that of FSH to 49.5; 120.3 and 63%, respectively, of the concentration recorded in the corresponding controls implanted with oil. Following the intrahypothalamic implantation of EB, the serum concentration of LH was lowered to 20.8; 67.4 and 68.1% and that of FSH to 48.8; 87.0 and 62.0% as compared to the cholesterol-implanted controls. The findings clearly suggest that a major part of the change in sensitivity to the negative feedback of estrogen occurs prior to the first preovulatory surge of gonadotrophins.