Estrogen Receptor in Rabbit Ovaries and Effects of Antiestrogen on Progesterone Production*

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Abstract
The present experiments examine the hypothesis that in pseudopregnant rabbits, a dramatic steroidogenic effect of estradiol on ovarian progesterone production is mediated by the estradiol-receptor complex mechanism. Such a hypothesis predicts that 1) estrogen receptor in the corpus luteum would accumulate rapidly in the cytosol after removal of a chronic Silastic capsule source of estradiol, and 2) the antiestrogen CI-628 (l-[2-(p-[α-(p-methoxyphenyl)β-nitrostyryl]phenoxy)-ethyl]pyrolidine monocitrate) would block the rescue of progesterone production that occurs upon reinsertion of the estradiolfilled capsules. Superovulation was induced, and on the second day after hCG (day 2), an estradiol-filled capsule was inserted beneath the skin in each rabbit. Progesterone in peripheral serum was 26 ± 4 ng/ml (mean ± SEM) on day 9 when the estradiol-filled capsule was removed; serum progesterone then declined to 7 ± 2 ng/ml within 18 h (day 10). Available cytoplasmic estrogen receptor in the corpus luteum was 799 ± 86 fmol/g wet weight (mean ± SEM) on day 9 when progesterone production was high; on day 10, 18 h after removal of the estradiol-filled capsule, available cytoplasmic receptor increased almost 300% to 2063 ± 174. In these same tissues, the level of 0.4 M KCl-extractable nuclear estrogen receptor was 387 ± 12 on day 9 but dropped to 111 ± 30 on day 10. The available estrogen receptor that accumulates in day 10 cytosols was translocated to the nucleus by an iv injection of estradiol or CI-628. If rabbits were reimplanted on day 10 with estradiol-filled capsules, serum progesterone rose to 31 ± 5 within 48 h. In contrast, when rabbits were given concomitant injections of CI-628 beginning 5 min before capsule reinsertion, progesterone remained low (7 ± 4 ng/ ml on day 12). Serum progesterone declined to less than 0.5 ng/ml on day 12 in rabbits treated with CI-628 but not reimplanted with estradiol-filled capsules. Apparently, the antiestrogen CI-628 may block estradiol-stimulated progesterone production by depleting available cytoplasmic estrogen receptor. Estrogen receptor translocated to the nucleus as a consequence of injections of CI-628 fails to support progesterone production.