A Comparative Study of Antiestrogen Action: Temporal Patterns of Antagonism of Estrogen Stimulated Uterine Growth and Effects on Estrogen Receptor Levels123

作者：Evan R. Ferguson, Benita S. Katzenellenbogen · 发表于：Endocrinology · 年份：1977 · DOI：10.1210/endo-100-5-1242 · 被引用次数：87 · 研究领域：Estrogen and related hormone effects、Effects and risks of endocrine disrupting chemicals

Studies were undertaken to ascertain the effects of structural modification of two well-known antiestrogens (CI-628 and U-11,100A) on their estrogenic and antiestrogenic potencies and temporal patterns of effectiveness in the immature rat uterus. Changes in the chemical structures of these anti-estrogens produce compounds with markedly different affinities for the uterine estrogen receptor as measured in an in vitro cell-free cytosol system; binding affinities relative to estradiol (100%) are: CI-628, 4%; CI-680, 34%; 94X1127 (94X),222%; U-11,100A (UA), 6%; and U-23,469 (U-23), 0.1%. Although all five antiestrogens (daily injections of 50 microng over three days) appear equally effective in stimulating 72 h uterine weight when given alone, or in blocking the estradiol-stimulated weight increase when given with estradiol, marked differences in their potencies are noted when the effects of the compounds are monitored beyond 24 h following a single injection. The compounds CI-628, CI-680 and UA (50 microng sc in saline), which have a methylated hydroxyl group (at the site analogous to the steroid position 3), show a prolonged maintenance of elevated levels of nuclear receptor (beyond 48 h) and elevated uterine weight (until 72 h); this correlates with a prolonged period of depressed cytoplasmic receptor levels (beyond 48 h) and prolonged uterine insensitivity to estrogen (beyond 36 h as monitored by 3 h wet weight response). In contrast, a single injection of 50 microng of 94X (...