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  • Title: RU 486 (mifepristone): induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys.
    Author: Neulen J, Williams RF, Hodgen GD.
    Journal: J Clin Endocrinol Metab; 1990 Oct; 71(4):1074-5. PubMed ID: 2401709.
    Abstract:
    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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