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Submitted on January 7, 2005
Accepted on April 15, 2005
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030; Microarray Core Facility Dept. of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, 77030 and Breast Center, Baylor College of Medicine, Houston, TX, 77030
* To whom correspondence should be addressed. E-mail: fdemayo{at}bcm.tmc.edu.
Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, affymetrix MG U74Av2 oligonucleotide arrays were used to identify the alterations in gene expression after acute and chronic P4 treatment. PRKO and wild-type mice were ovariectomized and then treated with vehicle or 1 mg P4 every 12 h. Mice were killed either 4 h after the first injection (acute P4 treatment) or after the fourth injection of P4 (chronic P4 treatment). At the genomic level, the major change in the gene expression after acute P4 treatment was the increase of 55 genes. Conversely, the major change in gene expression after chronic P4 treatment was an overall reduction in expression of 102 genes. In the analysis, retinoic acid metabolic genes: cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5 (ADH5) and aldehyde dehydrogenase 1a1 (Aldh1a1), kallikrein genes: Klk5 and Klk6, and specific transcription factors GATA-2 and Cited2 were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.
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