On the mechanism of the positive feedback action of estradiol on luteinizing hormone secretion in the rhesus monkey

In women and rhesus monkeys, both the negative and positive feedback actions of estradiol (E₂) on gonadotropin secretion (inhibition followed by a surge) can be exerted directly at the level of the pituitary gland. We have tested the hypothesis that the positive feedback action of E₂ represents but an 'escape' from its negative feedback inhibition of gonadotropin secretion consequent to a desensitization of the gonadotropes occasioned by sustained exposure to elevated concentrations of the steroid. We have attempted to replicate such a desensitization by blocking the negative feedback action of E₂ by the administration of a potent estrogen receptor antagonist devoid of any agonistic properties (ZM 182,780) to rhesus monkeys in the midfollicular phase of the menstrual cycle (n = 14). The estrogen antagonist, administered at a dose that in separate experiments completely blocked both the negative and the positive feedback effect of exogenous E₂ on pituitary LH secretion, failed to produce a surge-like increase in serum LH concentrations. The present results do not support the hypothesis that the LH surge is the consequence of the removal of the negative feedback action of E₂. Evidence is presented that ZM 182,780, in contrast to its inhibition of E₂-induced LH surges, cannot block the inhibition of hypothalamic GnRH pulse generator activity by E₂.