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How LH induces EGF\u2010like factor expression is unclear. In the present study, a rapid increase of phosphorylated cAMP response element binding protein (CREB) was observed after the activation of LH receptor by human chorionic gonadotropin. Large antral follicles from equine chorionic gonadotropin\u2010primed mice were cultured in medium with LH to stimulate the expression of EGF\u2010like factors. CREB phosphorylation was increased in granulosa cells; conversely KG\u2010501, a CREB functional inhibitor, significantly reduced LH\u2010induced gene expression of EGF\u2010like factors, oocyte meiotic resumption, and cumulus cell expansion. Reduction of CREB expression by <jats:italic>Creb<\/jats:italic> siRNA also repressed LH\u2010induced expression of EGF\u2010like factors in cultured granulosa cells. Inactivation of mitogen\u2010activated protein kinase (MAPK3\/1) by U0126 inhibited LH\u2010induced CREB phosphorylation and EGF\u2010like factors gene expression, whereas the activation of LH receptor increased Akt\/protein kinase B phosphorylation, which is involved in LH\u2010induced CREB phosphorylation and the expression of EGF\u2010like factors. Thus, LH induces MAPK3\/1 and Akt activation, both of which are required for the CREB\u2010promoted expression of EGF\u2010like factors in granulosa cells. <jats:italic>Mol. Reprod. Dev. 83: 1116\u20131127, 2016. \u00a9 2016 Wiley Periodicals, Inc<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrd.22753","type":"journal-article","created":{"date-parts":[[2016,10,22]],"date-time":"2016-10-22T19:56:38Z","timestamp":1477166198000},"page":"1116-1127","source":"Crossref","is-referenced-by-count":20,"title":["CREB activity is required for luteinizing hormone\u2010induced the expression of EGF\u2010like factors"],"prefix":"10.1002","volume":"83","author":[{"given":"Yakun","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology College of Biological Sciences, China Agricultural University Beijing People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqiong","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology College of Biological Sciences, China Agricultural University Beijing People's Republic of 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