Document Detail

The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2.
MedLine Citation:
PMID:  21330545     Owner:  NLM     Status:  MEDLINE    
During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy.
Quanxi Li; Athilakshmi Kannan; Francesco J DeMayo; John P Lydon; Paul S Cooke; Hiroyuki Yamagishi; Deepak Srivastava; Milan K Bagchi; Indrani C Bagchi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  331     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-18     Completed Date:  2011-03-08     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  912-6     Citation Subset:  IM    
Department of Comparative Biosciences, University of Illinois Urbana/Champaign, Urbana, IL 61820, USA.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / genetics*,  metabolism*
Cell Proliferation
Embryo Implantation / physiology*
Endometrium / drug effects,  metabolism*
Epithelial Cells / cytology,  drug effects,  metabolism
Epithelium / metabolism
Estradiol / metabolism
Estrogen Receptor alpha / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
Fibroblast Growth Factors / genetics,  metabolism*
Gene Expression Profiling
Mice, Inbred C57BL
Mice, Knockout
Mifepristone / pharmacology
Mucin-1 / metabolism
Progesterone / antagonists & inhibitors,  metabolism*,  pharmacology
Receptors, Fibroblast Growth Factor / metabolism
Receptors, Progesterone / metabolism
Signal Transduction*
Stromal Cells / cytology,  metabolism
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Estrogen Receptor alpha; 0/Hand2 protein, mouse; 0/Mucin-1; 0/Receptors, Fibroblast Growth Factor; 0/Receptors, Progesterone; 50-28-2/Estradiol; 57-83-0/Progesterone; 62031-54-3/Fibroblast Growth Factors; 84371-65-3/Mifepristone; EC Signal-Regulated MAP Kinases
Comment In:
Science. 2011 Feb 18;331(6019):863-4   [PMID:  21330520 ]

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