| LH-induced neuregulin 1 (NRG1) type III transcripts control granulosa cell differentiation and oocyte maturation. | |
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MedLine Citation:
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PMID: 21047912 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epidermal growth factor (EGF)-like factors [amphiregulin (AREG), betacellulin, and epiregulin] are induced by LH and activate the EGF receptor (ERBB1)/ERK1/2 pathway in granulosa cells and cumulus cells of preovulatory follicles to impact ovulation. However, the expression and roles of other ERBB family members and their ligands have not been explored in detail. Herein, we document that two transcripts of the neuregulin (Nrg1) gene are expressed in granulosa cells, and that the type III Nrg1 is induced during ovulation in an ERK1/2 and C/EBPβ-dependent manner. Western blotting shows that intact (75 kDa) and secreted (45 kDa) forms of neuregulin 1 (NRG1) are present in the ovary. NRG1 likely binds to ERBB3/ERBB2 complexes that are expressed in granulosa cells and cumulus cells. In cultured granulosa cells, NRG1 selectively stimulates the phosphorylation of AKT/PKB compared to ERK1/2. However, when granulosa cells were cultured with NRG1 and AREG, the phosphorylation of ERK1/2 was markedly enhanced as compared with that by AREG alone. Cotreatment with NRG1 and AREG also increased progesterone production. When cumulus-oocyte complexes (COCs) were cultured with both NRG1 and AREG, the matured oocytes exhibited significantly higher developmental competence as compared with that of oocytes cultured with AREG alone. Collectively, these results document that the expression of type III NRG1 is induced in granulosa cells during ovulation and that NRG1 enhances AREG-induced ERK1/2 phosphorylation in both granulosa cells and cumulus cells. The NRG1 pathway has two roles: one is to enhance AREG-induced progesterone production in granulosa cells, and the other is to regulate oocyte maturation by a cumulus cell-dependent mechanism. |
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Authors:
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Noritaka Noma; Ikko Kawashima; Heng-Yu Fan; Youko Fujita; Tomoko Kawai; Yoshinori Tomoda; Toshihiro Mihara; Joanne S Richards; Masayuki Shimada |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: Molecular endocrinology (Baltimore, Md.) Volume: 25 ISSN: 1944-9917 ISO Abbreviation: Mol. Endocrinol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: 2011-04-11 Revised Date: 2013-02-22 |
Medline Journal Info:
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Nlm Unique ID: 8801431 Medline TA: Mol Endocrinol Country: United States |
Other Details:
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Languages: eng Pagination: 104-16 Citation Subset: IM |
Affiliation:
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Laboratory of Reproductive Endocrinology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Cell Differentiation / drug effects* Cells, Cultured Chorionic Gonadotropin / pharmacology Cumulus Cells / cytology, drug effects, enzymology Embryonic Development / drug effects Enzyme Activation / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism Female Gene Expression Regulation / drug effects Glycoproteins / pharmacology Granulosa Cells / cytology*, drug effects, enzymology Humans Intercellular Signaling Peptides and Proteins / pharmacology Ligands Luteinizing Hormone / pharmacology* Mice Molecular Sequence Data Neuregulin-1 / genetics*, metabolism, pharmacology Oocytes / cytology*, drug effects Ovulation / drug effects Promoter Regions, Genetic / genetics Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / genetics, metabolism Receptor Protein-Tyrosine Kinases / metabolism Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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HD-07495/HD/NICHD NIH HHS; HD-16229/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chorionic Gonadotropin; 0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/Ligands; 0/Neuregulin-1; 0/Nrg1 protein, mouse; 0/RNA, Messenger; 117147-70-3/amphiregulin; 9002-67-9/Luteinizing Hormone; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
| Comments/Corrections | |
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