Document Detail

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.
MedLine Citation:
PMID:  20444920     Owner:  NLM     Status:  MEDLINE    
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.
Shee-Uan Chen; Ruey-Jien Chen; Jeng-Yi Shieh; Chia-Hung Chou; Chung-Wu Lin; Hsin-Fen Lu; Yu-Shih Yang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-05
Journal Detail:
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:
Created Date:  2010-08-05     Completed Date:  2010-08-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3982-92     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynecology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.
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MeSH Terms
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
Flavonoids / pharmacology
Immunoenzyme Techniques
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
Reg. No./Substance:
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

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