This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mukherjee, A.
Right arrow Articles by O'Malley, B. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mukherjee, A.
Right arrow Articles by O'Malley, B. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2006, p. 6571-6583, Vol. 26, No. 17
0270-7306/06/$08.00+0     doi:10.1128/MCB.00654-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Steroid Receptor Coactivator 2 Is Critical for Progesterone-Dependent Uterine Function and Mammary Morphogenesis in the Mouse

Atish Mukherjee,1 Selma M. Soyal,1 Rodrigo Fernandez-Valdivia,1 Martine Gehin,2 Pierre Chambon,2 Francesco J. DeMayo,1 John P. Lydon,1 and Bert W. O'Malley1*

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas,1 Institut Clinique de la Souris (ICS-IGBMC), BP10142, 67404 Illkirch Cedex, France2

Received 14 April 2006/ Accepted 18 June 2006

Although the essential involvement of the progesterone receptor (PR) in female reproductive tissues is firmly established, the coregulators preferentially enlisted by PR to mediate its physiological effects have yet to be fully delineated. To further dissect the roles of members of the steroid receptor coactivator (SRC)/p160 family in PR-mediated reproductive processes in vivo, state-of-the-art cre-loxP engineering strategies were employed to generate a mouse model (PRCre/+ SRC-2flox/flox) in which SRC-2 function was abrogated only in cell lineages that express the PR. Fertility tests revealed that while ovarian activity was normal, PRCre/+ SRC-2flox/flox mouse uterine function was severely compromised. Absence of SRC-2 in PR-positive uterine cells was shown to contribute to an early block in embryo implantation, a phenotype not shared by SRC-1 or -3 knockout mice. In addition, histological and molecular analyses revealed an inability of the PRCre/+ SRC-2flox/flox mouse uterus to undergo the necessary cellular and molecular changes that precede complete P-induced decidual progression. Moreover, removal of SRC-1 in the PRCre/+ SRC-2flox/flox mouse uterus resulted in the absence of a decidual response, confirming that uterine SRC-2 and -1 cooperate in P-initiated transcriptional programs which lead to full decidualization. In the case of the mammary gland, whole-mount and histological analysis disclosed the absence of significant ductal side branching and alveologenesis in the hormone-treated PRCre/+ SRC-2flox/flox mammary gland, reinforcing an important role for SRC-2 in cellular proliferative changes that require PR. We conclude that SRC-2 is appropriated by PR in a subset of transcriptional cascades obligate for normal uterine and mammary morphogenesis and function.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6205. Fax: (713) 798-5599. E-mail: berto{at}bcm.tmc.edu.

Molecular and Cellular Biology, September 2006, p. 6571-6583, Vol. 26, No. 17
0270-7306/06/$08.00+0     doi:10.1128/MCB.00654-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fernandez-Valdivia, R., Mukherjee, A., Creighton, C. J., Buser, A. C., DeMayo, F. J., Edwards, D. P., Lydon, J. P. (2008). Transcriptional Response of the Murine Mammary Gland to Acute Progesterone Exposure. Endocrinology 149: 6236-6250 [Abstract] [Full Text]  
  • Chopra, A. R., Louet, J.-F., Saha, P., An, J., DeMayo, F., Xu, J., York, B., Karpen, S., Finegold, M., Moore, D., Chan, L., Newgard, C. B., O'Malley, B. W. (2008). Absence of the SRC-2 Coactivator Results in a Glycogenopathy Resembling Von Gierke's Disease. Science 322: 1395-1399 [Abstract] [Full Text]  
  • Laws, M. J., Taylor, R. N., Sidell, N., DeMayo, F. J., Lydon, J. P., Gutstein, D. E., Bagchi, M. K., Bagchi, I. C. (2008). Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival. Development 135: 2659-2668 [Abstract] [Full Text]  
  • Lu, Z., Hardt, J., Kim, J.J. (2008). Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation. Mol Hum Reprod 14: 357-366 [Abstract] [Full Text]  
  • Zeng, Z., Velarde, M. C., Simmen, F. A., Simmen, R. C.M. (2008). Delayed Parturition and Altered Myometrial Progesterone Receptor Isoform A Expression in Mice Null for Kruppel-Like Factor 9. Biol. Reprod. 78: 1029-1037 [Abstract] [Full Text]  
  • He, B., Feng, Q., Mukherjee, A., Lonard, D. M., DeMayo, F. J., Katzenellenbogen, B. S., Lydon, J. P., O'Malley, B. W. (2008). A Repressive Role for Prohibitin in Estrogen Signaling. Mol. Endocrinol. 22: 344-360 [Abstract] [Full Text]  
  • Jeong, J.-W., Lee, K. Y., Han, S. J., Aronow, B. J., Lydon, J. P., O'Malley, B. W., DeMayo, F. J. (2007). The p160 Steroid Receptor Coactivator 2, SRC-2, Regulates Murine Endometrial Function and Regulates Progesterone-Independent and -Dependent Gene Expression. Endocrinology 148: 4238-4250 [Abstract] [Full Text]  
  • Lee, K. Y., Jeong, J.-W., Wang, J., Ma, L., Martin, J. F., Tsai, S. Y., Lydon, J. P., DeMayo, F. J. (2007). Bmp2 Is Critical for the Murine Uterine Decidual Response. Mol. Cell. Biol. 27: 5468-5478 [Abstract] [Full Text]  
  • Yuan, Y., Xu, J. (2007). Loss-of-Function Deletion of the Steroid Receptor Coactivator-1 Gene in Mice Reduces Estrogen Effect on the Vascular Injury Response. Arterioscler. Thromb. Vasc. Bio. 27: 1521-1527 [Abstract] [Full Text]  
  • Schumacher, M., Guennoun, R., Ghoumari, A., Massaad, C., Robert, F., El-Etr, M., Akwa, Y., Rajkowski, K., Baulieu, E.-E. (2007). Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System. Endocr. Rev. 28: 387-439 [Abstract] [Full Text]  
  • Wierman, M. E. (2007). Sex steroid effects at target tissues: mechanisms of action. Adv. Physiol. Educ. 31: 26-33 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»