The antiproliferative action of progesterone in uterine epithelium is mediated by hand2

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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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.

Original languageEnglish
Pages (from-to)912-916
Number of pages5
JournalScience
Volume331
Issue number6019
DOIs
Publication statusPublished - 2011 Feb 18

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Cite this

Li, Q., Kannan, A., DeMayo, F. J., Lydon, J. P., Cooke, P. S., Yamagishi, H., Srivastava, D., Bagchi, M. K., & Bagchi, I. C. (2011). The antiproliferative action of progesterone in uterine epithelium is mediated by hand2. Science, 331(6019), 912-916. https://doi.org/10.1126/science.1197454