Hormonal regulation of myometrial estrogen, progesterone, and oxytocin receptors in the pregnant and pseudopregnant hamster.

Estrogen receptor (Re) and progesterone receptor (Rp) concentrations were measured in the myometrium of hamster uterus during pregnancy and pseudopregnancy. Comparison of Re and Rp levels with serum estradiol and progesterone titers revealed that receptor concentration was low when progesterone was elevated during pregnancy and pseudopregnancy. However, Re and Rp levels increased when progesterone levels dropped at the end of each condition. In comparing serum estradiol relative to progesterone at the end of pregnancy and pseudopregnancy, it was discovered that Re and Rp recovery occurred not only when the estradiol to progesterone ratio increased (pseudopregnancy) but also when the ratio did not change (pregnancy). This suggested that serum progesterone was the primary determinant of receptor down-regulation, and this was confirmed by comparing the receptor recovery response to estrogen and progesterone withdrawal in the decidualized hamster uterus. Total Re levels increased to the same extent after progesterone withdrawal whether or not serum estradiol was maintained. When serum estrogen was maintained at a steady state, nuclear Re (nRe) increased within 4 h of progesterone withdrawal, and estrogen-dependent protein responses (Rp and oxytocin receptor) were obtained within 8 h. Thus, progesterone-induced down-regulation of nRe and estrogen-dependent proteins is rapidly reversed upon removal of hormone. The recovery response of Re, Rp, and oxytocin receptor to progesterone withdrawal can be blocked by cycloheximide treatment at 4 h, suggesting that receptor recovery involves protein synthesis. These results are consistent with the hypothesis that progesterone down-regulates the Re system by a selective action on nRe retention.