Insulin-like growth factor I gene expression in the uterus is stimulated by tamoxifen and inhibited by the pure antiestrogen ICI 182780.
Estrogen-induced uterine insulin-like growth factor I (IGF-I) expression has been demonstrated to mediate at least in part the uterotrophic action of estradiol. We studied the effects of tamoxifen, a partial antagonist to the estrogen receptor widely used in the treatment of breast cancer, and ICI 182780, a pure antagonist to the estrogen receptor, on uterine weight and uterine IGF-I gene expression in the rat. Tamoxifen increased uterine weight to 125% of control values and doubled uterine IGF-I expression. In contrast, ICI 182780 reduced uterine weight to 60% of control and uterine IGF-I gene expression to 13% of control. These results demonstrate for the first time that uterine IGF-I expression is a molecular marker that correlates with the effects of partial agonists and antagonists to the estrogen receptor on the uterus. Furthermore, the induction of uterine IGF-I expression by tamoxifen provides a molecular mechanism to account for the uterotrophic effects which are commonly seen with tamoxifen therapy and which have been associated with endometrial neoplasia.
Huynh
H T
HT
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Pollak
M
M
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004965:Estrogen Antagonists; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I