A Mechanism for Regression of the Rabbit Corpus Luteum: Uterine-Induced Loss of Luteal Responsiveness to 17β-Estradiol12

Abstract

Estradiol-17.beta. was administered continuously to pseudopregnant rabbits to determine whether this treatment would prevent regression of corpora lutea and prolong the period of progesterone secretion. Estradiol was administered via a Silastic capsule placed s.c. either on the day of mating (day 0) or the day after mating to vasectomized males. These estradiol implants maintained serum estradiol at approximately 3-fold normal concentrations. Blood samples were taken on alternate days, beginning on day 2 and ending on day 22 or 28 at which time the corpora lutea were removed, weighed and examined histologically. Mean serum progesterone concentrations in untreated pseudopregnant rabbits reached a peak value of 13.4 ng/ml on day 10 and by day 18 had fallen to 1.5 ng/ml. Continuous estradiol treatment did not enhance luteal weight or serum progesterone levels, which were 14.5 and 2.1 ng/ml on days 10 and 18, respectively. The inability of estradiol to extend the period of progesterone secretion was not due to altered metabolism of estradiol, since the serum concentrations of estradiol were not different on days 10 and 22 in rabbits with an estradiol implant (.apprx. 15 pg/ml). The corpora lutea regressed in the presence of elevated levels of estradiol, which is considered to be the principal luteotropic hormone in the rabbit. In pseudopregnant rabbits which were hysterectomized and treated with estradiol, serum progesterone increased to a peak value of 12.4 ng/ml on days 10-12 and remained elevated at approximately 11 ng/ml throughout the period of observation (day 28). Hysterectomized rabbits without estradiol treatment showed a gradual decline in serum progesterone after days 10-12 to levels of 2-3 ng/ml on day 20, and these levels were maintained through the remainder of the experiment (day 28). To exclude possible intraovarian influences on progesterone secretion, ectopic corpora lutea were established beneath the kidney capsule. The period of elevated progesterone in rabbits with ectopic corpora lutea with or without an estradiol implant was similar to that in pseudopregnant rabbits with corpora lutea in situ. This indicates that luteal regression is not caused by intraovarian hormone changes. A decline in serum estradiol is not a prerequisite for regression of corpora lutea at the end of pseudopregnancy. The ovary is not a privileged site for normal luteolysis. The uterus has a primary role in limiting the life span of the corpus luteum by reducing luteal responsiveness to estradiol.