COUPLING OF DUAL SIGNALING PATHWAYS - EPIDERMAL GROWTH-FACTOR ACTION INVOLVES THE ESTROGEN-RECEPTOR
COUPLING OF DUAL SIGNALING PATHWAYS - EPIDERMAL GROWTH-FACTOR ACTION INVOLVES THE ESTROGEN-RECEPTOR
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DOI：
10.1073/pnas.89.10.4658
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发表时间：
1992-05-15
影响因子：
11.1
通讯作者：
KORACH, KS
中科院分区：
文献类型：
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作者：
IGNARTROWBRIDGE, DM;NELSON, KG;KORACH, KS
表皮生长因子(EGF)复制了雌激素对小鼠生殖道的许多影响，并可能部分介导了雌激素诱导的生长和分化。本研究旨在探讨EGF在整个动物体内诱导雌激素样作用的机制。成年去卵巢小鼠肾被膜下植入缓释微丸给药。雌激素受体拮抗剂ICI164,384可减弱EGF或己烯雌酚(5-mU-g/kg)对子宫DNA合成和磷脂酰肌醇脂代谢的诱导。此外，EGF模拟了雌激素在增强雌激素受体的核定位和形成一种独特形式的雌激素受体方面的作用，这种雌激素受体仅存在于细胞核中。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而在小鼠子宫中诱导类似于雌激素的效应。多肽生长因子和类固醇激素受体之间的相互作用对于我们理解正常生长和分化的调控以及细胞外有丝分裂原信号向细胞核的传递机制具有重要意义。
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-mu-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.