Oncotarget

Research Papers: Pathology:

Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus

Fabiola F. Mehta, Jieun Son, Sylvia C. Hewitt, Eunjung Jang, John P. Lydon, Kenneth S. Korach and Sang-Hyuk Chung _

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Oncotarget. 2016; 7:17455-17467. https://doi.org/10.18632/oncotarget.8159

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Abstract

Fabiola F. Mehta1, Jieun Son1, Sylvia C. Hewitt2, Eunjung Jang1, John P. Lydon3, Kenneth S. Korach2 and Sang-Hyuk Chung1

1 Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA

2 Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

3 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Correspondence to:

Sang-Hyuk Chung, email:

Keywords: progesterone receptor, estrogen receptor α, epithelium, female reproductive tract, mouse model, Pathology Section

Received: August 04, 2015 Accepted: March 02, 2016 Published: March 17, 2016

Abstract

While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor α (ERα) in the female reproductive tracts. Using knock−in mouse models expressing ERα mutants, we determined that the DNA−binding domain (DBD) and AF2 domain of ERα were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERα AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERα DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERα. Epithelial ERα was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus.


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