Effects of withdrawal of exogenous estradiol from pseudopregnant rabbits: transient nature of loss of luteal function and reversal of estradiol-induced suppression of luteinizing hormone-responsive adenylyl cyclase.

Abstract

We have reported in recent studies that exogenous estradiol (E2) suppresses luteal LH-responsive adenylyl cyclase activity in pseudopregnant rabbits. The purpose of the present study was to determine whether this suppression is reversible. High or low level E2-filled Silastic capsules or empty capsules were sc implanted in day 5 pseudopregnant rabbits. On day 8 of pseudopregnancy, the high level E2 implants were either sham replaced, replaced with low level E2 implants, or replaced with empty capsules. The low level E2 implants and empty capsules were sham replaced. Animals from each of the five resulting groups were killed on days 9-12 of pseudopregnancy (1, 2, 3, and 4 days postimplant manipulation). As previously reported using an intermittent injection protocol, exogenous E2 had little effect upon serum progesterone concentrations. Both high and low level E2 implants suppressed the luteal LH-responsive adenylyl cyclase, but the suppression due to the low level E2 implants was not as great as that for the high level E2 implants. Within 24 h of switching from high to low level E2 implants, LH-responsive adenylyl cyclase activity increased from the level found for animals with high level E2 throughout to that found for animals with low level E2 throughout. Total withdrawal of exogenous E2 resulted in a precipitous fall in serum progesterone concentrations, as predicted by previous studies. However, within 4 days of withdrawal, both serum progesterone and luteal LH-responsive adenylyl cyclase activity had returned to control values. E2 implants also suppressed serum LH concentrations and follicular LH-responsive adenylyl cyclase activities. Both of these effects were reversed within 24-48 h after implant withdrawal. We conclude, therefore, that effects of exogenous E2 are reversible and that the previously reported E2-induced dependency upon exogenous E2 is related to the experimental protocol used.