The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium: Putative role of interleukin-1β
Endocrinology, ISSN: 0013-7227, Vol: 148, Issue: 7, Page: 3205-3213
2007
- 43Citations
- 22Captures
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Metrics Details
- Citations43
- Citation Indexes43
- 43
- CrossRef34
- Captures22
- Readers22
- 22
Article Description
CRH targets the human myometrium during pregnancy. The efficiency of CRH actions is determined by expression of functional receptors (CRH-R), which are dynamically regulated. Studies in myometrial tissue biopsies using quantitative RT-PCR demonstrated that the onset of labor, term or preterm, is associated with a significant 2- to 3-fold increase in CRH-R1 mRNA levels. Detailed analysis of myometrial CRH-R1 mRNA variants showed a decline of the pro-CRH-R1 mRNA encoding the CRH-R1β variant during labor and increased mRNA levels of CRH-R1d mRNA. Studies in myometrial cells identified IL-1β as an important regulator of myometrial CRH-R1 gene expression because prolonged treatment of myometrial cells with IL-1β (1 ng/ml) for 18 h induced expression of CRH-R1 mRNA levels by 1.5- to 2-fold but significantly attenuated CRH-R1β mRNA expression by 70%. In contrast, IL-1β had no effect on CRH-R1d mRNA expression. Studies using specific inhibitors suggest that ERK1/2, p38 MAPK, and downstream nuclear translocation of nuclear factor-κB mediate IL-1β effects on myometrial CRH-R1 gene. However, the increased CRH-R1 mRNA expression was associated with a dampening of the receptor efficacy to activate the adenylyl cyclase/cAMP signaling cascade. Thus, our findings suggest that IL-1β is an important regulator of CRH-R1 expression and functional activity, and this interaction might play a role in the transition of the uterus from quiescence to active contractions necessary for the onset of parturition. Copyright © 2007 by The Endocrine Society.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34347246325&origin=inward; http://dx.doi.org/10.1210/en.2007-0095; http://www.ncbi.nlm.nih.gov/pubmed/17431005; https://academic.oup.com/endo/article/148/7/3205/2501942; https://dx.doi.org/10.1210/en.2007-0095; https://academic.oup.com/endo/article-abstract/148/7/3205/2501942?redirectedFrom=fulltext
The Endocrine Society
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