Insulin-like growth factor I gene expression in the uterus is stimulated by tamoxifen and inhibited by the pure antiestrogen ICI 182780.

Abstract

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.