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 a ctions of estradiol (E-2) on gonadotropin secretion (inhibition follow ed by a surge) can be exerted directly at the level of the pituitary g land. We have tested the hypothesis that the positive feedback action of E-2 represents but an ''escape'' from its negative feedback inhibit ion of gonadotropin secretion consequent to a desensitization of the g onadotropes occasioned by sustained exposure to elevated concentration s of the steroid. We have attempted to replicate such a desensitizatio n by blocking the negative feedback action off, by the administration of a potent estrogen receptor antagonist devoid of any agonistic prope rties (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 E-2 on pituitary LH sec retion, failed to produce a surge-like increase in serum LH concentrat ions. The present results do not support the hypothesis that the LH su rge is the consequence of the removal of the negative feedback action off,. Evidence is presented that ZM 182,780, in contrast to its inhibi tion of E-2-induced LH surges, cannot block the inhibition of hypothal amic GnRH pulse generator activity by E-2.