Journal of Clinical Endocrinology & Metabolism, Vol 71, 1074-1075, Copyright © 1990 by Endocrine Society

ARTICLES

RU 486 (mifepristone): induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys

J Neulen, RF Williams and GD Hodgen
Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk 23510.

This study was designed to investigate the effect of the anti-progestin RU 486 on estradiol receptor concentrations in the endometrium of monkeys given physiologic estrogen replacement therapy. Estradiol-17 beta (E2) silastic implants were inserted infrascapularly into 12 long- term ovariectomized cynomolgus monkeys (Macaca fascicularis) resulting in an average peripheral serum level of approximately 100 pg/ml estradiol. On day 6 of E2 treatment four treatment groups were initiated: Group I--estradiol implants only; Group II--estradiol implants plus 11 mumol progesterone/kg bodyweight in sesame oil via im injections on days 6,7,8; Group III--estradiol implants plus 2.2 mumol RU 486/kg in sesame oil via im injections on day 6,7,8; Group IV-- estradiol implants plus 11 mumol RU 486/kg via im injections on day 6,7,8. On treatment day 9 endometrial biopsies were removed by hysterotomies. Cytosolic and nuclear estradiol receptor contents of tissues were estimated by charcoal method. In Group I, the tissue contained 376 +/- 123 pmol bound H-E2/g protein; the nuclear portion was about 16%. In Group II, the tissue contained 216 +/- 64 pmol bound 3H-E2/g protein; the nuclear portion was only 8%. In Group III, tissue contained 654 +/- 47 pmol bound H-E2/g protein; the nuclear portion was about 22%. In Group IV, the tissue contained 1198 +/- 172 pmol bound 3H- E2/g protein; the nuclear portion was about 17%. Scatchard plot analysis indicated a Kd app of 1.04 x 10(-9) M. This study demonstrates that after physiologic E2 replacement therapy estradiol receptor concentrations rise dramatically following anti-progestin treatment; this effect was dose dependent.

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