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-17β (E2) silastic implants were inserted infrascapularly into 12 long-term ovariectomized cynomolgus monkeys (Macaca fascicularis) resulting in an average peripheral serum levelt 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 umol progesterone/kg bodyweight in sesame oil via im injections on days 6, 7, 8; Group III - estradiol implants plus 2.2 umol RU 486/kg in sesame oil via im injections on day 6, 7, 8; Group IV - estradiol implants plus 11 pmol 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 3H-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 H-E2/g protein; the nuclear portion was about 17%. Scatchard plot analysis indicated a Kd app of 1.04 × 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. © 1990 by The Endocrine Society.
