Ignar-Trowbridge D M, Nelson K G, Bidwell M C, Curtis S W, Washburn T F, McLachlan J A, Korach K S
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
Proc Natl Acad Sci U S A. 1992 May 15;89(10):4658-62. 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 micrograms/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.
表皮生长因子（EGF）可重现雌激素对小鼠雌性生殖道的许多作用，并可能部分介导雌激素诱导的生长和分化。本研究旨在探讨EGF在整体动物中引发类雌激素作用的机制。通过植入肾被膜下的缓释微丸将EGF给予成年去卵巢小鼠。雌激素受体拮抗剂ICI 164,384可减弱EGF或给予强效雌激素己烯雌酚（5微克/千克）所诱导的子宫DNA合成及磷脂酰肌醇脂质周转。此外，EGF模拟了雌激素对雌激素受体核定位增强以及在细胞核中特有的一种雌激素受体形式形成的作用。这些结果表明，EGF可能通过EGF信号通路与经典雌激素受体之间的相互作用，在小鼠子宫中诱导出与雌激素类似的作用。多肽生长因子与类固醇激素受体之间存在相互作用的证明，可能对于我们理解正常生长和分化的调节以及细胞外有丝分裂原信号向细胞核传递的机制具有重要意义。
