| Human chorionic gonadotropin up-regulates expression of myeloid cell leukemia-1 protein in human granulosa-lutein cells: implication of corpus luteum rescue and ovarian hyperstimulation syndrome. | |
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MedLine Citation:
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PMID: 20444920 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: The corpus luteum is a dynamic endocrine structure with periodic development and regression during menstrual cycles. Its lifespan can be prolonged by human chorionic gonadotropin (hCG). However, the signal mechanisms of this phenomenon remain unclear. OBJECTIVE: Our objective was to investigate the molecular mechanisms of hCG in the maintenance of the viability of granulosa-lutein cells. DESIGN: Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the effects of hCG on the survival of cultured granulosa-lutein cells. The signal pathway inducing antiapoptotic protein was investigated. RESULTS: hCG enhanced viability of granulosa-lutein cells through antiapoptosis but not proliferation, because the apoptotic marker of annexin V was decreased, but the proliferative markers of Ki67 and proliferating cell nuclear antigen were not increased. Myeloid cell leukemia-1 (Mcl-1) protein, but not B-cell lymphoma protein-2 or B-cell lymphoma protein-xL, was significantly induced by hCG and LH. The granulosa-lutein cells secreted vascular endothelial growth factor that induced endothelial permeability. Mcl-1 small interfering RNA increased DNA fragmentation and diminished the antiapoptotic effect of hCG. hCG induced Mcl-1 expression through the LH/hCG receptor, adenylate cyclase, protein kinase A, and cAMP response element-binding protein signal pathway. Flavopiridol inhibited Mcl-1 production, released cytochrome c, and induced apoptosis of granulosa-lutein cells. CONCLUSIONS: We first demonstrate that hCG prevents apoptosis of granulosa-lutein cells through the induction of Mcl-1 protein via the LH/hCG receptor and a cAMP response element-binding protein-dependent pathway. We may have found the molecular mechanism for luteal rescue during early pregnancy. Mcl-1 prevents apoptosis and increases cell viability but not proliferation as mechanisms for luteal rescue. Mcl-1 is a key molecule of hCG signaling. |
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Authors:
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Shee-Uan Chen; Ruey-Jien Chen; Jeng-Yi Shieh; Chia-Hung Chou; Chung-Wu Lin; Hsin-Fen Lu; Yu-Shih Yang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-05 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-08-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 3982-92 Citation Subset: AIM; IM |
Affiliation:
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Department of Obstetrics and Gynecology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Apoptosis / drug effects Blotting, Western Cell Proliferation / drug effects Cell Survival / drug effects Cells, Cultured Chorionic Gonadotropin / pharmacology* Corpus Luteum / cytology, drug effects, metabolism Dose-Response Relationship, Drug Female Flavonoids / pharmacology Humans Immunoenzyme Techniques Immunohistochemistry Luteal Cells / cytology, drug effects, metabolism* Ovarian Hyperstimulation Syndrome / metabolism Piperidines / pharmacology Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism* RNA, Small Interfering Receptors, LH / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Chorionic Gonadotropin; 0/Flavonoids; 0/Piperidines; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/Receptors, LH; 0/myeloid cell leukemia sequence 1 protein; 146426-40-6/flavopiridol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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