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Selective Inhibition of Estrogen-regulated Gene Expression in Vivo by the Pure Antiestrogen ICI 182,780¹

Departments of Integrative Biology, Pharmacology, and Physiology [S. M. H., C. C., G. M. S.] and Obstetrics, Gynecology, and Reproductive Sciences [S. M. H.], University of Texas Health Sciences Center, Houston, Texas 77225, and Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030 [L.M.]

Estrogen-stimulated cell proliferation is thought to be mediated by the induction of growth-regulatory factors. Abnormal regulation of such factors may be associated with tumorigenesis. Two such factors, vascular endothelial growth factor and c-fos, are rapidly induced in the uterus by estrogens. We show that the induction of these transcripts by 17ß-estradiol or tamoxifen is selectively blocked by the pure antiestrogen ICI 182,780 in a dose-dependent manner. This indicates that induction of the two genes requires different levels of estrogen receptor or that their induction occurs by different mechanisms. This suggests that selective dose-dependent antagonism of estrogen-dependent transcription may be possible in target tissues and tumors.

¹ This research was supported by a Grant-in-Aid from the American Heart Association, Texas Affiliate, and by NIH Grants HD-08615 and ES-06995.

² To whom requests for reprints should be addressed, at Department of Integrative Biology, Pharmacology, and Physiology, University of Texas Medical School, P. O. Box 20708, 6431 Fannin Street, Houston, TX 77225. Phone: (713) 500-7459; Fax: (713) 500-7455; E-mail: shyder@farmr1.med.uth.tmc.edu.

Received 4/ 2/97. Accepted 5/15/97.

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