Chorionic Gonadotropin Regulates Prostaglandin E Synthase via a Phosphatidylinositol 3-Kinase-Extracellular Regulatory Kinase Pathway in a Human Endometrial Epithelial Cell Line: Implications for Endometrial Responses for Embryo Implantation

被引:32
作者
Banerjee, Prajna [2 ]
Sapru, Kavita [1 ]
Strakova, Zuzana [1 ]
Fazleabas, Asgerally T. [1 ]
机构
[1] Univ Illinois, Dept Obstet Gynecol, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA
关键词
LUTEINIZING-HORMONE RECEPTOR; LUTROPIN-CHORIOGONADOTROPIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; GRANULOSA-CELLS; LEYDIG-CELLS; MENSTRUAL-CYCLE; MOUSE UTERUS; LUTROPIN/CHORIOGONADOTROPIN RECEPTOR; AROMATASE EXPRESSION; SIGNAL-TRANSDUCTION;
D O I
10.1210/en.2009-0394
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Successful implantation necessitates modulation of the uterine environment by the embryo for a specific period of time during the menstrual cycle. Infusion of chorionic gonadotropin (CG) into the oviducts of baboons to mimic embryo transit induces a myriad of morphological, biochemical, and molecular changes in the endometrium. Endometrial epithelial cells from both baboons and humans when stimulated by CG in vitro, activates a cAMP-independent MAPK pathway leading to prostaglandin E-2 (PGE(2)) synthesis. This study shows that in the human endometrial cell line, HES, CG, acting via its G-protein coupled receptor, phosphorylates protein kinase B, c-Raf, and ERK1/2 in a phosphatidylinositol 3-kinase (PI3K)-dependent manner. Furthermore, ERK1/2 phosphorylation is independent of the signaling paradigms of G alpha(s), G alpha(I), and epidermal growth factor receptor (EGFR) transactivation, typical of gonadal cells, indicating an alternative signaling pattern in the endometrium. After phosphorylation by CG, ERK1/2 translocates to the nucleus in a time-dependent manner. Downstream of ERK1/2, CG activates the nuclear transcription factor, Elk1, also in a PI3K-MAPK-dependent manner. Lastly, we show that in HES cells, this pathway regulates the expression of the microsomal enzyme PGE2 synthase (mPTGES), a terminal prostanoid synthase responsible for PGE2 synthesis. CG regulates the mPTGES promoter and also induces mPTGES synthesis in HES cells via the PI3K-ERK1/2 pathway. We suggest that this alternative PI3K-ERK-Elk pathway activated by CG regulates prostaglandin production by the endometrial epithelium and serves as an early trigger to prepare the endometrium for implantation. (Endocrinology 150: 4326-4337, 2009)
引用
收藏
页码:4326 / 4337
页数:12
相关论文
共 74 条
  • [1] Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response
    Aoyama, T
    Matsui, T
    Novikov, M
    Park, J
    Hemmings, B
    Rosenzweig, A
    [J]. CIRCULATION, 2005, 111 (13) : 1652 - 1659
  • [2] Expression of the mature luteinizing hormone receptor in rodent urogenital and adrenal tissues is developmentally regulated at a posttranslational level
    Apaja, PM
    Aatsinki, JT
    Rajaniemi, HJ
    Petäjä-Repo, UE
    [J]. ENDOCRINOLOGY, 2005, 146 (08) : 3224 - 3232
  • [3] Embryo implantation: the molecular mechanism remains elusive
    Aplin, J. D.
    [J]. REPRODUCTIVE BIOMEDICINE ONLINE, 2006, 13 (06) : 833 - 839
  • [4] Membrane translocation of P-Rex1 is mediated by G protein βγ subunits and phosphoinositide 3-kinase
    Barber, Mark A.
    Donald, Sarah
    Thelen, Sylvia
    Anderson, Karen E.
    Thelen, Marcus
    Welch, Heidi C. E.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (41) : 29967 - 29976
  • [5] A system for stable expression of short interfering RNAs in mammalian cells
    Brummelkamp, TR
    Bernards, R
    Agami, R
    [J]. SCIENCE, 2002, 296 (5567) : 550 - 553
  • [6] Decidualization regulates the expression of the endometrial chorionic gonadotropin receptor in the primate
    Cameo, Paula
    Szmidt, Maciej
    Strakova, Zuzana
    Mavrogianis, Patricia
    Sharpe-Timms, Kathy L.
    Fazleabas, Asgerally T.
    [J]. BIOLOGY OF REPRODUCTION, 2006, 75 (05) : 681 - 689
  • [7] Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids
    Chakraborty, I
    Das, SK
    Wang, J
    Dey, SK
    [J]. JOURNAL OF MOLECULAR ENDOCRINOLOGY, 1996, 16 (02) : 107 - 122
  • [8] Loss of cyclooxygenase-2 retards decidual growth but does not inhibit embryo implantation or development to term
    Cheng, JG
    Stewart, CL
    [J]. BIOLOGY OF REPRODUCTION, 2003, 68 (02) : 401 - 404
  • [9] Gonadotropins activate proteolysis and increase invasion through protein kinase A and phosphatidylinositol 3-kinase pathways in human epithelial ovarian cancer cells
    Choi, JH
    Choi, KC
    Auersperg, N
    Leung, PCK
    [J]. CANCER RESEARCH, 2006, 66 (07) : 3912 - 3920
  • [10] Coffer PJ, 1998, BIOCHEM J, V335, P1