Changing Ratios of Nuclear Estrone to Estradiol Binding in Endometrium at Implantation: Regulation by Chorionic Gonadotropin and Progesterone during Rescue of the Primate Corpus Luteum *

Nuclear binding of 17β-estradiol (NE2R) and estrone (NE1R) was measured in monkey endometrium at different times in the nonfertile menstrual cycle and compared to that during implantation in the fertile menstrual cycle. After finding significant differences in nuclear estrogen binding in the periimplantation interval, we mimicked natural rescue of the corpus luteum by administering either exogenous hCG or progesterone to unmated monkeys during the late luteal phase. In all, endometriectomies were performed on 44 female rhesus monkeys. Besides the 27 unmated monkeys that provided endometrial tissue from the midfoliicular phase through the luteal phase, 9 cycling females were mated on day 12 after the onset of menses, 4 others received hCG injections on cycle day 23, and 4 more received Silastic implants containing progesterone on day 23. Total concentrations of NE1R and NE2R were measured on days 8, 12, 15, 18, and 24 of the menstrual cycle (unmated monkeys) and on the day 24 for both the mated and treated (hCG or progesterone) monkeys. The ratio of the mean of NE1R to that of NE2R were less than 1 (range, 0.34–0.80) throughout the nonfertile menstrual cycle. Among the 9 mated monkeys, 4 had ratios of 0.70, like that of unmated females on cycle day 24,concurrent with a mean serum progesterone concentration of 0.5 ± 0.1 ng/ml (mean ± SE); this progesterone level is typical of the late luteal phase in the nonfertile cycle. In contrast, the remaining 5 mated monkeys had a NE1R to NE2R ratio of 2.50 in endometrial tissue. Further, there was an abrupt increase of progesterone in the circulation during the late luteal phase (cycle day 24), reaching 3.6 ± 1 ng/ml. This late luteal phase increase in serum progesterone is characteristic of the rescue of the corpus luteum during initiation of implantation in these primates. Among the other groups, a similar change in nuclear estrogen receptor ratios was found in the endometrium of nonmated monkeys having received exogenous hCG or progesterone in the periimplantation interval; their nuclear estrogen receptor ratios were 3.5 and 2.3, respectively. We conclude that in the periimplantation interval (approximately cycle day 24), the ratio of NE1R to NE2R rose significantly in three circumstances: 1) during spontaneous rescue of the corpus luteam in normal pregnancies; 2) after artificial rescue of the corpus luteum by hCG; and 3) after simulated rescue of the corpus luteam by the administration of progesterone in the late luteal phase. These findings show that the late luteal phase rise in serum progesterone during the fertile menstrual cycie is responsible for the relative increase in NE1R in endometrial tissue at implantation and that the preimplantation blastocyst is probably not involved in this change.