Coupling of Dual Signaling Pathways: Epidermal Growth Factor Action Involves the Estrogen Receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 10; pp. 4658 - 4662
• Main Authors: Ignar-Trowbridge, Diane M., Nelson, Karen G., Bidwell, Mark C., Curtis, Sylvia W., Washburn, Todd F., McLachlan, John A., Korach, Kenneth S.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15-05-1992; National Acad Sciences; National Academy of Sciences
• Subjects: activity; Animals; Biochemistry; Biological and medical sciences; Cell Nucleus - metabolism; Cell physiology; Delayed-Action Preparations; Diethylstilbestrol - pharmacology; DNA; DNA biosynthesis; DNA Replication - drug effects; epidermal growth factor; Epidermal Growth Factor - pharmacology; Estradiol - analogs & derivatives; Estradiol - metabolism; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Estrogen receptors; Estrogens; Female; Fundamental and applied biological sciences. Psychology; Hormones; induction; Inositol Phosphates - metabolism; Lipid metabolism; Lipids; Medical research; Memory interference; Mice; Mice, Inbred Strains; Molecular and cellular biology; Nuclear interactions; Ovariectomy; phosphatidylinositol; Phosphatidylinositols - metabolism; Polyunsaturated Alkamides; receptors; Receptors, Estrogen - drug effects; Receptors, Estrogen - metabolism; Receptors, Estrogen - physiology; Responses to growth factors, tumor promotors, other factors; Rodents; role; Signal Transduction - drug effects; Steroids; turnover; Uterus; Uterus - drug effects; Uterus - physiology; Rodentia; Estrogen; DNA synthesis; Metabolism; Phosphatidylinositol; Vertebrata; Mammalia; Epidermal growth factor; Mouse; Uterus; Cross reaction; Antagonist; Sex steroid hormone; Hormonal receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.10.4658

Epidermal growth factor (EGF) reproduces many of the effects of estrogen on the murine female reproductive tract and may partially mediate estrogen-induced growth and differentiation. This study was performed to investigate the mechanism by which EGF elicits estrogen-like actions in the whole animal. EGF was administered to adult ovariectomized mice by slow release pellets implanted under the kidney capsule. The induction of uterine DNA synthesis and phosphatidylinositol lipid turnover by EGF or administration of diethylstilbestrol (5 μ g/kg), a potent estrogen, was attenuated by the estrogen receptor antagonist ICI 164,384. Furthermore, EGF mimicked the effects of estrogen on enhanced nuclear localization of the estrogen receptor and the formation of a unique form of the estrogen receptor found exclusively in the nucleus. These results suggest that EGF may induce effects similar to those of estrogen in the mouse uterus by an interaction between the EGF signaling pathway and the classical estrogen receptor. The demonstration of cross-talk between polypeptide growth factors and steroid hormone receptors may be of importance to our understanding of the regulation of normal growth and differentiation as well as the mechanisms of transmission of extracellular mitogen signals to the nucleus.