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.