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Molecular and Cellular Biology, March 2008, p. 1770-1782, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01556-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Peroxisome Proliferator-Activated Receptor {gamma} Is a Target of Progesterone Regulation in the Preovulatory Follicles and Controls Ovulation in Mice{triangledown}

Jaeyeon Kim,1 Marcey Sato,1 Quanxi Li,2 John P. Lydon,3 Francesco J. DeMayo,3 Indrani C. Bagchi,2 and Milan K. Bagchi1*

Departments of Molecular and Integrative Physiology,1 Veterinary Biosciences, University of Illinois Urbana-Champaign, Urbana, Illinois,2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas3

Received 24 August 2007/ Returned for modification 4 October 2007/ Accepted 24 December 2007

The progesterone receptor (PR) plays a critical role during ovulation. Mice lacking the PR gene are anovulatory due to a failure in the rupture of the preovulatory follicles. The pathways that operate downstream of PR to control ovulation are poorly understood. Using gene expression profiling, we identified peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) as a target of regulation by PR in the granulosa cells of the preovulatory follicles during the ovulatory process. To investigate the function of PPAR{gamma} during ovulation, we created a conditional knockout mouse in which this gene was deleted via Cre-Lox-mediated excision in granulosa cells. When these mutant mice were subjected to gonadotropin-induced superovulation, the preovulatory follicles failed to rupture and the number of eggs released from the mutant ovaries declined drastically. Gene expression analysis identified endothelin-2, interleukin-6, and cyclic GMP-dependent protein kinase II as novel targets of regulation by PPAR{gamma} in the ovary. Our studies also suggested that cycloxygenase 2-derived metabolites of long-chain fatty acids function as endogenous activating ligands of PPAR{gamma} in the preovulatory follicles. Collectively, these studies revealed that PPAR{gamma} is a key mediator of the biological actions of PR in the granulosa cells and activation of its downstream pathways critically controls ovulation.

* Corresponding author. Mailing address: University of Illinois, MC-114, 534 Burrill Hall, 407 S. Goodwin, Urbana, IL 61801. Phone: (217) 244-5054. Fax: (217) 333-1133. E-mail: mbagchi{at}life.uiuc.edu

{triangledown} Published ahead of print on 2 January 2008.

Molecular and Cellular Biology, March 2008, p. 1770-1782, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01556-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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