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Insulin-like Growth Factor I Gene Expression in the Uterus Is Stimulated by Tamoxifen and Inhibited by the Pure Antiestrogen ICI 182780¹

Departments of Medicine and Oncology, McGill University, and the Lady Davis Research Institute of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2

² To whom request for reprints should be addressed, at Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec, Canada H3T 1E2.

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.

¹ Supported by a grant from the National Cancer Institute of Canada to M. P. and by the Reisman Family Foundation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/18/93. Accepted 10/19/93.

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