This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by HALUSKA, G. J. Articles by BRENNER, R. M. Search for Related Content PubMed PubMed Citation Articles by HALUSKA, G. J. Articles by BRENNER, R. M.

Uterine Estrogen Receptors Are Increased by RU486 in Late Pregnant Rhesus Macaques but not after Spontaneous Labor^*

Division of Reproductive Biology and Behavior, Oregon Regional Primate Research Center (G.J.H., N.B. W., M.J.N., R.M.B.) Beaverton, Oregon 97006
The Department of Obstetrics/Gynecology, Oregon Health Sciences University (M.J.N.) Portland, Oregon 97201

Address requests for reprints to: Dr. George J. Haluska, Oregon Regional Primate Research Center, 505 NW 185th Avenue, Beaverton, Oregon 97006.

Progesterone withdrawal as a mechanism for parturition in primates is controversial. The progesterone antagonist RU486, given in late pregnancy to rhesus monkeys at a dose of 47 mmol/kg·day (20 mg/kg·day), causes an increase in uterine activity, but not the expected increase in amniotic fluid prostaglandins or cervical dilatation. We, therefore, studied the effect of RU486 on estrogen receptor (ER) localization and concentration in reproductive tract tissues in rhesus monkeys during late gestation and after spontaneous labor at term. Distribution of ER in pregnant uterine tissues was studied by immunocytochemical techniques and quantified by a biochemical assay, both of which employed a monoclonal antibody specific for ER.

ER was not present in amnion and chorion by immunocytochemical investigation; however, a significant increase in receptor staining was seen in decidua and myometrium after RU486 treatment compared to that in both pregnant control tissues and parturient tissues. Sucrose gradient assay of nuclear (n) and cytosolic (c) ER revealed a low level of ER (expressed as fmol of estradiol bound/mg of DNA) in pregnant and parturient decidua (pregnant: nER = 7.3 ± 2.4, cER = 17.1 ± 6.4; parturient, nER = 7.7 ± 3.1, cER = 16.4 ± 8.8) and myometrium (pregnant: nER = 21.7 ± 4.1, cER = 20.8 ± 5.3; parturient: nER = 30.0 ± 2.8, cER = 10.7 ± 6.7). In contrast, tissues collected from RU486-treated animals contained high levels of ER in decidua (nER = 52.3 ± 16.8, cER = 240.5 ± 145.3) and myometrium (nER = 77.0 ± 19.2; cER = 66.5 ± 31.6).

We conclude that 1) the increase in ER in decidua and myometrium after RU486 treatment is the result of a decrease in the inhibitory action of progesterone on ER and documents the progesterone receptor antagonism by RU486 during induced myometrial contractility in late pregnant rhesus monkeys; 2) the absence of ER from amnion and chorion indicates that the normally observed increase in prostaglandin production by rhesus fetal membranes during labor is not mediated by ER; and 3) the absence of a change in the concentration of ER in decidua and myometrium from pregnant control monkeys and those in spontaneous labor indicates that an increase in ER (and, by inference, a withdrawal of receptor-mediated progesterone inhibition) is not part of the normal events in preparation for parturition in primates.

^* This work was supported by Grant RR-OO163 from the NIH and Grants HD-O6159 and HD-18185 from the NICHHD. Presented in part at the 35th Annual Meeting of the Society for Gynecologic Investigation, Baltimore, MD, March 17-20, 1988. Publication 1682 of the Oregon Regional Primate Research Center.

Received April 17, 1989.

This article has been cited by other articles:

				G. X. Rosario, D. N. Modi, G. Sachdeva, D. D. Manjramkar, and C. P. Puri Morphological events in the primate endometrium in the presence of a preimplantation embryo, detected by the serum preimplantation factor bioassay Hum. Reprod., January 1, 2005; 20(1): 61 - 71. [Abstract] [Full Text] [PDF]

				S. Mesiano Myometrial Progesterone responsiveness and the Control of Human Parturition Reproductive Sciences, May 1, 2004; 11(4): 193 - 202. [Abstract] [PDF]

				H.A. Rodriguez, L. Kass, J. Varayoud, J.G. Ramos, H.H. Ortega, M. Durando, M. Munoz-de-Toro, and E.H. Luque Collagen remodelling in the guinea-pig uterine cervix at term is associated with a decrease in progesterone receptor expression Mol. Hum. Reprod., December 1, 2003; 9(12): 807 - 813. [Abstract] [Full Text] [PDF]

				S. Mesiano, E.-C. Chan, J. T. Fitter, K. Kwek, G. Yeo, and R. Smith Progesterone Withdrawal and Estrogen Activation in Human Parturition Are Coordinated by Progesterone Receptor A Expression in the Myometrium J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2924 - 2930. [Abstract] [Full Text] [PDF]

				W. X. Wu, X. H. Ma, G. C. S. Smith, and P. W. Nathanielsz Differential distribution of ERalpha and ERbeta mRNA in intrauterine tissues of the pregnant rhesus monkey Am J Physiol Cell Physiol, January 1, 2000; 278(1): C190 - C198. [Abstract] [Full Text] [PDF]

				X. Fang, S. Wong, and B. F. Mitchell Effects of RU486 on Estrogen, Progesterone, Oxytocin, and Their Receptors in the Rat Uterus during Late Gestation Endocrinology, July 1, 1997; 138(7): 2763 - 2768. [Abstract] [Full Text] [PDF]