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) expressi on has been demonstrated to mediate at least in part the uterotrophic action of estradiol. We studied the effects of tamoxifen, a partial an tagonist to the estrogen receptor widely used in the treatment of brea st cancer, and ICI 182780, a pure antagonist to the estrogen receptor, on uterine weight and uterine IGF-I gene expression in the rat. Tamox ifen increased uterine weight to 125% of control values and doubled ut erine 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 expr ession is a molecular marker that correlates with the effects of parti al agonists and antagonists to the estrogen receptor on the uterus. Fu rthermore, the induction of uterine IGF-I expression by tamoxifen prov ides a molecular mechanism to account for the uterotrophic effects whi ch are commonly seen with tamoxifen therapy and which have been associ ated with endometrial neoplasia.