Uterine steroid receptor changes associated with progesterone withdrawal during pregnancy and pseudopregnancy in rabbits.

Abstract

Cytosolic and nuclear progesterone (P) and estrogen (E) receptors (PR and ER, respectively) were measured in uterine tissues of rabbits at the end of pregnancy (days 25, 27, 29, 30, and 31 and 0-10 h postpartum) and pseudopregnancy (days 13 and 18). At both times, plasma P concentrations fell dramatically after a period of prolonged elevation, effecting changes in uterine function. Plasma concentrations of P remained elevated until day 29 of pregnancy and then fell continuously until postpartum, whereas plasma estradiol levels did not change. The numbers of nuclear ER and PR were constant from days 25-29. Concomitant with the fall in plasma P on day 30, levels of nuclear ER and PR doubled and remained elevated on day 31 and postpartum. In all cases, the numbers of nuclear receptors were negatively correlated with P concentrations. The number of cystosolic ER in the myometrium increased on day 30 of pregnancy and remained elevated on day 31 and postpartum. Although levels of cytosolic ER in the endometrium appeared to rise similarly, the change was not significant. The number of cytosolic PR in endometrium and myometrium did not change significantly. Between days 13 and 18 of pseudopregnancy, plasma P declined while plasma estradiol remained constant, as during pregnancy. At this time, cytosolic PR increased 4-fold, and nuclear PR doubled. Nuclear ER also increased between days 13 and 18, but the apparent increase in cytosolic ER was not significant. These data suggest that receptors for both steroids increase as the ratio of plasma estradiol to P increases at the end of pregnancy and pseudopregnancy. Surprisingly, nuclear PR levels are highest at term, when the influence of P in suppressing myometrial activity and preventing the onset of labor is removed. Thus, in the rabbit, the level of PR does not directly reflect the physiological response to P.