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Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: Potential role in functional progesterone withdrawal at term
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Karteris, Emmanouil, Zervou, Sevasti, Pang, Yefei, Dong, Jing, Hillhouse, Edward W., Randeva, Harpal S. and Thomas, Peter (2006) Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: Potential role in functional progesterone withdrawal at term. MOLECULAR ENDOCRINOLOGY, 20 (7). pp. 1519-1534. doi:10.1210/me.2005-0243 ISSN 0888-8809.
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Official URL: http://dx.doi.org/10.1210/me.2005-0243
Abstract
Progestin withdrawal is a crucial event for the onset of labor in many mammalian species. However, in humans the mechanism of a functional progestin withdrawal is unclear, because progestin concentrations do not drop in maternal plasma preceding labor. We report the presence of two novel functional membrane progestin receptors (mPRs), mPR alpha and mPR beta, in human myometrium that are differentially modulated during labor and by steroids in vitro. The mPRs are coupled to inhibitory G proteins, resulting in a decline in cAMP levels and increased phosphorylation of myosin light chain, both of which facilitate myometrial contraction. Activation of mPRs leads to transactivation of PR-B, the first evidence for cross-talk between membrane and nuclear PRs. Progesterone activation of the mPRs leads also to a decrease of the steroid receptor coactivator 2. Our data indicate the presence of a novel signaling pathway mediated by mPRs that may result in a functional progestin withdrawal, shifting the balance from a quiescent state to one of contraction.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > RC Internal medicine | ||||
Journal or Publication Title: | MOLECULAR ENDOCRINOLOGY | ||||
Publisher: | ENDOCRINE SOC | ||||
ISSN: | 0888-8809 | ||||
Official Date: | July 2006 | ||||
Dates: |
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Volume: | 20 | ||||
Number: | 7 | ||||
Number of Pages: | 16 | ||||
Page Range: | pp. 1519-1534 | ||||
DOI: | 10.1210/me.2005-0243 | ||||
Publication Status: | Published |
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