Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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}illinois.edu (I.C.B.); mbagchi{at}life.illinois.edu (M.K.B.)


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Murine Uterine Transcriptome, Responsive to Steroid Receptor Coactivator-2, Reveals Transcription Factor 23 as Essential for Decidualization of Human Endometrial Stromal Cells.
R. Kommagani, M. M. Szwarc, E. Kovanci, C. J. Creighton, B. W. O'Malley, F. J. DeMayo, and J. P. Lydon (2014)
Biol Reprod 90, 75
   Abstract »    Full Text »    PDF »
Differential Gene Expression Profiling of Mouse Uterine Luminal Epithelium During Periimplantation.
S. Xiao, H. Diao, F. Zhao, R. Li, N. He, and X. Ye (2014)
Reproductive Sciences 21, 351-362
   Abstract »    Full Text »    PDF »
Fibroblast Growth Factor Receptor Two (FGFR2) Regulates Uterine Epithelial Integrity and Fertility in Mice.
J. Filant, F. J. DeMayo, J. K. Pru, J. P. Lydon, and T. E. Spencer (2014)
Biol Reprod 90, 7
   Abstract »    Full Text »    PDF »
Uterine glands: development, function and experimental model systems.
P. S. Cooke, T. E. Spencer, F. F. Bartol, and K. Hayashi (2013)
Mol. Hum. Reprod. 19, 547-558
   Abstract »    Full Text »    PDF »
Progesterone Receptor Signaling in the Microenvironment of Endometrial Cancer Influences Its Response to Hormonal Therapy.
D. M. Janzen, M. A. Rosales, D. Y. Paik, D. S. Lee, D. A. Smith, O. N. Witte, M. L. Iruela-Arispe, and S. Memarzadeh (2013)
Cancer Res. 73, 4697-4710
   Abstract »    Full Text »    PDF »
KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing.
S. Ray and J. W. Pollard (2012)
PNAS 109, E1334-E1343
   Abstract »    Full Text »    PDF »
Progesterone Inhibits Uterine Gland Development in the Neonatal Mouse Uterus.
J. Filant, H. Zhou, and T. E. Spencer (2012)
Biol Reprod 86, 146
   Abstract »    Full Text »    PDF »
Brief Exposure to Progesterone During a Critical Neonatal Window Prevents Uterine Gland Formation in Mice.
P. S. Cooke, G. C. Ekman, J. Kaur, J. Davila, I. C. Bagchi, S. G. Clark, P. J. Dziuk, K. Hayashi, and F. F. Bartol (2012)
Biol Reprod 86, 63
   Abstract »    Full Text »    PDF »
Evidence for a conserved function of heart and neural crest derivatives expressed transcript 2 in mouse and human decidualization.
D. V. Huyen and B. M. Bany (2011)
Reproduction 142, 353-368
   Abstract »    Full Text »    PDF »
A Hand to Support the Implantation Window.
S. C. Hewitt and K. S. Korach (2011)
Science 331, 863-864
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882