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Science 289 (5485): 1751-1754

Copyright © 2000 by the American Association for the Advancement of Science

Subgroup of Reproductive Functions of Progesterone Mediated by Progesterone Receptor-B Isoform

Biserka Mulac-Jericevic, Robert A. Mullinax, Francesco J. DeMayo, John P. Lydon, Orla M. Conneely*

Progesterone regulates reproductive function through two intracellular receptors, progesterone receptor-A (PR-A) and progesterone receptor-B (PR-B), that arise from a single gene and function as transcriptional regulators of progesterone-responsive genes. Although in vitro studies show that PR isoforms can display different transcriptional regulatory activities, their physiological significance is unknown. By selective ablation of PR-A in mice, we show that the PR-B isoform modulates a subset of reproductive functions of progesterone by regulation of a subset of progesterone-responsive target genes. Thus, PR-A and PR-B are functionally distinct mediators of progesterone action in vivo and should provide suitable targets for generation of tissue-selective progestins.

Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: orlac{at}bcm.tmc.edu

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H. A. Molenda, C. P. Kilts, R. L. Allen, and M. J. Tetel (2003)
Biol Reprod 69, 1449-1457
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Unfolding the Action of Progesterone Receptors.
X. Li and B. W. O'Malley (2003)
J. Biol. Chem. 278, 39261-39264
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Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform.
B. Mulac-Jericevic, J. P. Lydon, F. J. DeMayo, and O. M. Conneely (2003)
PNAS 100, 9744-9749
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Selective Interactions of Kruppel-like Factor 9/Basic Transcription Element-binding Protein with Progesterone Receptor Isoforms A and B Determine Transcriptional Activity of Progesterone-responsive Genes in Endometrial Epithelial Cells.
X.-L. Zhang, D. Zhang, F. J. Michel, J. L. Blum, F. A. Simmen, and R. C. M. Simmen (2003)
J. Biol. Chem. 278, 21474-21482
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