Chobotova Katya, Muchmore Mary-Elizabeth, Carver Janet, Yoo Hyung-J, Manek Sanjiv, Gullick William J, Barlow David H, Mardon Helen J
Nuffield Department of Obstetrics and Gynecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom OX3 9DU.
J Clin Endocrinol Metab. 2002 Dec;87(12):5769-77. doi: 10.1210/jc.2002-020069.
Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is implicated in a variety of biological processes, including reproduction. Previous studies describe increased levels of HB-EGF in the human endometrium during the midsecretory stage of the menstrual cycle, suggesting a function for HB-EGF in implantation of the human blastocyst. Here we have investigated the expression and function of the soluble and transmembrane forms of HB-EGF in the human endometrium. We show that the expression of the transmembrane form of HB-EGF in the human endometrium is modulated according to the stage of the menstrual cycle. We present data demonstrating that both the soluble and transmembrane forms of HB-EGF induce DNA synthesis in human endometrial stromal cells. Furthermore, TNFalpha has a cooperative effect on HB-EGF, EGF, TGFalpha, and betacellulin-induced DNA synthesis in stromal cells, suggesting roles for the EGF family and TNFalpha in regeneration and maturation of human endometrium. Induction of DNA synthesis by HB-EGF and its modulation by TNFalpha in endometrial stromal cells are mediated by the EGF receptor and not the HB-EGF receptor ErbB4. Our data suggest key functions for HB-EGF, TNFalpha, and the EGF receptor in endometrial maturation, via autocrine/paracrine and juxtacrine pathways, in preparation for embryo implantation.
肝素结合表皮生长因子（HB-EGF）是表皮生长因子（EGF）家族的一员，参与包括生殖在内的多种生物学过程。先前的研究表明，在月经周期的分泌中期，人子宫内膜中HB-EGF水平升高，提示HB-EGF在人胚泡着床中发挥作用。在此，我们研究了人子宫内膜中可溶性和跨膜形式的HB-EGF的表达及功能。我们发现，人子宫内膜中跨膜形式的HB-EGF的表达根据月经周期阶段而受到调节。我们提供的数据表明，可溶性和跨膜形式的HB-EGF均可诱导人子宫内膜基质细胞的DNA合成。此外，肿瘤坏死因子α（TNFα）对HB-EGF、EGF、转化生长因子α（TGFα）和β细胞素诱导的基质细胞DNA合成具有协同作用，提示EGF家族和TNFα在人子宫内膜再生和成熟中发挥作用。HB-EGF诱导子宫内膜基质细胞DNA合成及其受TNFα的调节是由EGF受体而非HB-EGF受体ErbB4介导的。我们的数据表明，HB-EGF、TNFα和EGF受体通过自分泌/旁分泌和邻分泌途径在子宫内膜成熟中发挥关键作用，为胚胎着床做准备。
