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Semin Reprod Med 2007; 25(1): 005-013
DOI: 10.1055/s-2006-956771
Copyright © 2007 by Thieme Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Myometrial Progesterone Responsiveness

Sam Mesiano1
  • 1Department of Reproductive Biology, Case Western Reserve University; Department of Obstetrics/Gynecology, University Hospitals Case Medical Center, Cleveland, Ohio
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Publication History

Publication Date:
05 January 2007 (online)

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ABSTRACT

Progesterone actions in human pregnancy are controlled by the extent of myometrial progesterone responsiveness. Current progress in unraveling the biochemistry for myometrial progesterone responsiveness at the genomic and nongenomic levels have lead to novel hypotheses regarding the role of these pathways in the hormonal control of human pregnancy and parturition. For the genomic pathway, progesterone interacts with the type-B nuclear progesterone receptor (nPR-B), which decreases expression of contraction-associated genes. For the nongenomic pathway, progesterone interacts with membrane-associated PRs (mPRs) to modulate directly intracellular Ca2+ and cyclic adenosine monophosphate (cAMP) levels. During most of human pregnancy the genomic and nongenomic pathway cooperate to maintain myometrial relaxation. However, at parturition the relaxing actions of progesterone are nullified by changes in myometrial progesterone responsiveness. This occurs by (1) increased expression of the nPR variants (e.g., PR-A and/or PR-C) and changes in nPR coregulator levels that together repress the transcriptional activity of PR-B; and (2) increased expression of specific mPRs, especially mPRß, which augments contractility by decreasing intracellular cAMP. Functional progesterone withdrawal may be induced by locally produced prostaglandins that alter myometrial nPR expression. This may be an important physiological link between the control of parturition and the immune/inflammatory process.

KEYWORDS

Progesterone responsiveness - myometrium - human pregnancy - genomic - nongenomic

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Sam MesianoPh.D. 

Department of Reproductive Biology, Case Western Reserve University; Department of Obstetrics/Gynecology, University Hospitals of Cleveland

11100 Euclid Ave, Cleveland, OH 44106-5034

Email: sam.mesiano@cwru.edu

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