Relationship of estradiol to luteal function in the cycling baboon.

Since exogenous 17 beta-estradiol (E2) is luteolytic in some primates, it is reasonable to conclude that endogenous E2 is the naturally occurring luteolytic substance. However, a link between endogenous E2 and spontaneous luteolysis has not been demonstrated. In an attempt to understand the function of E2 in spontaneous luteolysis, we employed the antiestrogen clomiphene. We administered E2, clomiphene, or E2 plus clomiphene to baboons during the luteal phase and measured systemic levels of estrone, E2, progesterone (P), and LH, E2 alone depressed the concentrations of P and bioassayable LH prematurely. The length of the luteal phase was significantly shortened (12.8 +/- 0.9 vs. 15.8 +/- 0.4 days for sham controls; P less than 0.01). Clomiphene blocked the luteolytic effect of exogenous E2, resulting in P levels which were not significantly different (P greater than 0.01) from control and a luteal phase of normal length (15.0 +/- 1.0 days). Treatment with E2 alone caused serum LH concentrations to decrease. The administration of clomiphene alone maintained circulating LH at early to midluteal phase levels but did not alter luteal phase P concentrations or prolong the length of the luteal phase (15.6 +/- 0.4 days). The results suggest that E2-induced luteolysis is a result of the withdrawal of luteotropic support from the (corpus) luteum, while spontaneous luteolysis is a result of some other mechanism which may not involve endogenous E2.