Differential suppression of progesterone receptors by progesterone in the reproductive tract of female macaques

Ovariectomized cynomolgus macaques were treated with implants of estradiol (E₂) for 14 days. Some animals then received an additional implant of progesterone (P) for 7-14 more days. After treatment with either E₂ alone or with E₂ plus P we removed the reproductive tracts and measured nuclear and cytosolic P receptors by exchange assay. In addition we used steroid radioimmunoassays(RIA) to measure levels of E₂ and P in parallel aliquots of the nuclear and cytosolic fractions. P treatment reduced the concentrations of E₂ in nuclear and cytosolic fractions in the cervix, endometrium, myometrium and oviduct compared to the amounts present after 14 days of E₂ these data are consistent with many reports that P treatment significantly lowers the amount of nuclear and cytosolic estrogen receptors in all of these tissues. In the oviduct, myometrium and cervix both cytosolic and nuclear P receptor levels were lowered during P action. In the endometrium, however, P treatment reduced the amount of P receptor only in the cytosolic but not the nuclear fraction. RIA determinations of the amount of P retained in nuclear fractions of the P-treated animals indicate that P levels were significantly elevated only in the nuclei obtained from endometrium. This specific increase in the retention of P by endometrial nuclei during P action is consistent with the specific retention of P receptor by endometrial nuclei. These results lead to the unexpected conclusion that the stimulatory effects of P as expressed in the maintenance of the progestational state in the primate endometrium may require higher levels of occupied nuclear P receptor than do the suppressive effects of P as expressed in oviductal atrophy, diminished cervical secretion and myometrial quieting.