NEGATIVE FEEDBACK EFFECTS OF ESTROGEN ON LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE OCCUR IN PUBERTAL, BUT NOT PREPUBERTAL, OVARIECTOMIZED FEMALE RHESUS-MONKEYS

In a previous study we found that ovariectomy resulted in an increase in both LHRH release and LH release in pubertal monkeys but not in prepubertal monkeys. To determine whether this castration-induced LHRH increase is due to the removal of estrogen, in the present study, the effects of estradiol benzoate (EB, 30 mug/kg body wt) on in vivo LHRH release were examined using a push-pull perfusion method in prepubertal (age 15-19 months, n = 5), early pubertal (24-29 months, n = 5), and midpubertal (36-48 months, n = 5) female rhesus monkeys that were ovariectomized 3 to 5 months earlier. LHRH in 10-min perfusate fractions from the stalk-median eminence was measured from -6 to +24 h after EB injection. Circulating LH levels were also monitored over the same period at various intervals. EB decreased LH levels in early pubertal and midpubertal monkeys, whereas it did not cause any significant effects on LH release in the prepubertal monkey. EB also resulted in suppression of LHRH release in both early and midpubertal monkeys; mean LHRH release before EB in the early and midpubertal groups was 6.6 +/- 0.6 and 7.0 +/- 0.6 pg/ml . 10 min, respectively. EB decreased mean LHRH release beginning 3 h after EB with the nadir occurring at 18-21 h after EB (1.0 +/- 0.2 pg/ml . 10 min) in early pubertal monkeys and 21-24 h after EB (1.2 +/- 0.1 pg/ml . 10 min) in midpubertal monkeys. Decrease of mean LHRH release was due to a decrease in LHRH pulse amplitude and basal release but not pulse frequency. Oil injection alone (control) failed to suppress LHRH and LH release. In contrast to the results in pubertal monkeys, mean LHRH release in prepubertal monkeys was not altered by EB (before EB, 1.1 +/- 0.2 pg/ml . 10 min; 18-21 h after EB. 1.5 +/- 6.3 pg/ml . 10 min). These results suggest that the LHRH neurosecretory system in pubertal monkeys is responsive to the negative feedback effects of estrogen. However, the fact that estradiol failed to suppress LHRH release in prepubertal monkeys indicates that the LHRH neurosecretory system and/or its regulatory systems are not sensitive to estradiol before the onset of puberty. These findings are consistent with the hypothesis that the increase in pulsatile LHRH release at the onset of puberty is not dependent on changes in ovarian steroid feedback mechanisms.