title: CREB activity is required for luteinizing hormone-induced the expression of EGF-like factors.
abstract: A surge of luteinizing hormone (LH) from the pituitary gland induces the expression of the epidermal growth factor (EGF)-like factors, which triggers oocyte maturation, cumulus expansion, and ovulation. How LH induces EGF-like 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-primed mice were cultured in medium with LH to stimulate the expression of EGF-like factors. CREB phosphorylation was increased in granulosa cells; conversely KG-501, a CREB functional inhibitor, significantly reduced LH-induced gene expression of EGF-like factors, oocyte meiotic resumption, and cumulus cell expansion. Reduction of CREB expression by Creb siRNA also repressed LH-induced expression of EGF-like factors in cultured granulosa cells. Inactivation of mitogen-activated protein kinase (MAPK3/1) by U0126 inhibited LH-induced CREB phosphorylation and EGF-like factors gene expression, whereas the activation of LH receptor increased Akt/protein kinase B phosphorylation, which is involved in LH-induced CREB phosphorylation and the expression of EGF-like factors. Thus, LH induces MAPK3/1 and Akt activation, both of which are required for the CREB-promoted expression of EGF-like factors in granulosa cells. Mol. Reprod. Dev. 83: 1116-1127, 2016. © 2016 Wiley Periodicals, Inc.
authors: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors: Yakun
authors: Y
authors: Wang
authors: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors: Xiaoqiong
authors: X
authors: Hao
authors: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors: Jing
authors: J
authors: Yang
authors: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors: Jia
authors: J
authors: Li
authors: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
authors: Meijia
authors: M
authors: Zhang
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D002070:Butadienes; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009570:Nitriles; C113580:U 0126; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D051057:Proto-Oncogene Proteins c-akt; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3