| Smoothelin-like 1 protein is a bifunctional regulator of the progesterone receptor during pregnancy. | |
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MedLine Citation:
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PMID: 21771785 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During pregnancy, uterine smooth muscle (USM) coordinately adapts its contractile phenotype in order to accommodate the developing fetus and then prepare for delivery. Herein we show that SMTNL1 plays a major role in pregnancy to promote adaptive responses in USM and that this process is specifically mediated through interactions of SMTNL1 with the steroid hormone receptor PR-B. In vitro and in vivo SMTNL1 selectively binds PR and not other steroid hormone receptors. The physiological relationship between the two proteins was also established in global gene expression and transcriptional reporter studies in pregnant smtnl1(-/-) mice and by RNA interference in progesterone-sensitive cell lines. We show that the contraction-associated and progestin-sensitive genes (oxytocin receptor, connexin 43, and cyclooxygenase-2) and prolactins are down-regulated in pregnant smtnl1(-/-) mice. We suggest that SMTNL1 is a bifunctional co-regulator of PR-B signaling and thus provides a molecular mechanism whereby PR-B is targeted to alter gene expression patterns within USM cells to coordinately promote alterations in USM function during pregnancy. |
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Authors:
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Khaldon Bodoor; Beata Lontay; Rachid Safi; Douglas H Weitzel; David Loiselle; Zhengzheng Wei; Szabolcs Lengyel; Donald P McDonnell; Timothy A Haystead |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-07-19 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-05 Completed Date: 2011-12-05 Revised Date: 2011-12-09 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 31839-51 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Female Gene Expression Profiling Gene Expression Regulation / physiology Mice Muscle Contraction / physiology Muscle Proteins / metabolism, physiology* Muscle, Smooth / metabolism Myometrium / metabolism, physiology Phosphoproteins / metabolism, physiology* Pregnancy Progestins Prolactin Receptors, Progesterone / metabolism* Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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R37 DK048807-18/DK/NIDDK NIH HHS; R56DK065954-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CHASM protein, mouse; 0/Muscle Proteins; 0/Phosphoproteins; 0/Progestins; 0/Receptors, Progesterone; 9002-62-4/Prolactin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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