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Science 331 (6019): 912-916

Copyright © 2011 by the American Association for the Advancement of Science

The Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2

Quanxi Li,1 Athilakshmi Kannan,1 Francesco J. DeMayo,2 John P. Lydon,2 Paul S. Cooke,1 Hiroyuki Yamagishi,3 Deepak Srivastava,4 Milan K. Bagchi,5,* Indrani C. Bagchi1,*

Abstract: 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.

1 Department of Comparative Biosciences, University of Illinois Urbana/Champaign, Urbana, IL 61820, USA.
2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
3 Keio University School of Medicine, Tokyo 160-8582, Japan.
4 The Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94158, USA.
5 Department of Molecular and Integrative Physiology, University of Illinois Urbana/Champaign, Urbana, IL 61820, USA.

* To whom correspondence should be addressed. E-mail: ibagchi{at} (I.C.B.); mbagchi{at} (M.K.B.)

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