Home LiteratureArticle Details
PMID: 19443782 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility.

Science (New York, N.Y.) ·Vol. 324 ·No. 5929 ·2009-05-15 ·Pages 938-41

Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM, Richards JS

Abstract

A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Because the signaling molecules RAS and ERK1/2 (extracellular signal-regulated kinases 1 and 2) are activated by an LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBPbeta (CCAAT/Enhancer-binding protein-beta) is a critical downstream mediator of ERK1/2 activation. Thus, ERK1/2 and C/EBPbeta constitute an in vivo LH-regulated signaling pathway that controls ovulation- and luteinization-related events.

MeSH Terms
Animals CCAAT-Enhancer-Binding Protein-beta/genetics,metabolism Enzyme Activation Female Fertility Gene Expression Profiling Granulosa Cells/enzymology,metabolism Luteinizing Hormone/metabolism MAP Kinase Signaling System Meiosis Mice Mice, Inbred C57BL Mice, Transgenic Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3/metabolism Oocytes/physiology Ovarian Follicle/physiology Ovulation Phosphorylation
Chemicals
CCAAT-Enhancer-Binding Protein-beta Luteinizing Hormone Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Fan Heng-Yu
Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Liu Zhilin
Shimada Masayuki
Sterneck Esta
Johnson Peter F
Hedrick Stephen M
Richards Joanne S
References (19)
19 references, click to expand
  1. Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation.
    Mol Cell Biol. 2007 Mar;27(5):1914-24 PMID: 17194751
  2. Conditional ablation of C/EBP beta demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis.
    Oncogene. 2006 Feb 23;25(8):1272-1276 PMID: 16205634
  3. Intercellular communication in the mammalian ovary: oocytes carry the conversation.
    Science. 2002 Jun 21;296(5576):2178-80 PMID: 12077402
  4. FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A.
    Cell Signal. 2006 Sep;18(9):1351-9 PMID: 16616457
  5. MAP kinases.
    Chem Rev. 2001 Aug;101(8):2449-76 PMID: 11749383
  6. Selective expression of KrasG12D in granulosa cells of the mouse ovary causes defects in follicle development and ovulation.
    Development. 2008 Jun;135(12):2127-37 PMID: 18506027
  7. Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is required for hepatocyte proliferation induced by TGF alpha.
    Mol Cell. 1999 Dec;4(6):1087-92 PMID: 10635333
  8. Perspective: the ovarian follicle--a perspective in 2001.
    Endocrinology. 2001 Jun;142(6):2184-93 PMID: 11356661
  9. Follicle stimulating hormone (FSH) activates the p38 mitogen-activated protein kinase pathway, inducing small heat shock protein phosphorylation and cell rounding in immature rat ovarian granulosa cells.
    Endocrinology. 1998 Jul;139(7):3353-6 PMID: 9645711
  10. Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice.
    Science. 1999 Nov 12;286(5443):1374-7 PMID: 10558995
  11. Role of MAPKs in development and differentiation: lessons from knockout mice.
    Biochimie. 2006 Sep;88(9):1091-8 PMID: 16854512
  12. Mitogen-activated protein kinase mediates luteinizing hormone-induced breakdown of communication and oocyte maturation in rat ovarian follicles.
    Endocrinology. 2005 Mar;146(3):1236-44 PMID: 15576461
  13. Low expression of COX-2, reduced cumulus expansion, and impaired ovulation in SULT1E1-deficient mice.
    FASEB J. 2007 Jun;21(8):1893-901 PMID: 17341680
  14. An essential role for C/EBPbeta in female reproduction.
    Genes Dev. 1997 Sep 1;11(17):2153-62 PMID: 9303532
  15. The role of erk1 and erk2 in multiple stages of T cell development.
    Immunity. 2005 Oct;23(4):431-43 PMID: 16226508
  16. Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse.
    Endocrinology. 2002 Jun;143(6):2221-32 PMID: 12021186
  17. EGF-like growth factors as mediators of LH action in the ovulatory follicle.
    Science. 2004 Jan 30;303(5658):682-4 PMID: 14726596
  18. Luteinizing hormone signaling in preovulatory follicles involves early activation of the epidermal growth factor receptor pathway.
    Mol Endocrinol. 2008 Apr;22(4):924-36 PMID: 18187604
  19. Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulosa cells: key roles for prostaglandin synthase 2 and progesterone receptor.
    Mol Endocrinol. 2006 Jun;20(6):1352-65 PMID: 16543407
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1171396
Published
2009-05-15
Pages
938-41
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2847890
Subset
IM
Grants
NICHD NIH HHS · HD16229 · United States
NICHD NIH HHS · U54 HD007495-366896 · United States
NICHD NIH HHS · R01 HD016229-27A2 · United States
NIAID NIH HHS · R01 AI021372 · United States
NICHD NIH HHS · U54 HD007495 · United States
Intramural NIH HHS · United States
NICHD NIH HHS · HD07495 · United States
NICHD NIH HHS · R01 HD016229 · United States
NIAID NIH HHS · R01 AI021372-26 · United States
NICHD NIH HHS · HD07165 · United States
Databases
GEO
GSE15135
Corrections
CommentIn
PMID: 19443772
External Links
PubMed source DOI: 10.1126/science.1171396 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2