Publication Date:
2011-02-19
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320855/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320855/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Quanxi -- Kannan, Athilakshmi -- DeMayo, Francesco J -- Lydon, John P -- Cooke, Paul S -- Yamagishi, Hiroyuki -- Srivastava, Deepak -- Bagchi, Milan K -- Bagchi, Indrani C -- U54 HD055787-01A1/HD/NICHD NIH HHS/ -- U54HD055787/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2011 Feb 18;331(6019):912-6. doi: 10.1126/science.1197454.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Comparative Biosciences, University of Illinois Urbana/Champaign, Urbana, IL 61820, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21330545" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
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
;
Female
;
Fibroblast Growth Factors/genetics/*metabolism
;
Gene Expression Profiling
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Mifepristone/pharmacology
;
Mucin-1/metabolism
;
Phosphorylation
;
Pregnancy
;
Progesterone/antagonists & inhibitors/*metabolism/pharmacology
;
Receptors, Fibroblast Growth Factor/metabolism
;
Receptors, Progesterone/metabolism
;
*Signal Transduction
;
Stromal Cells/cytology/metabolism
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
