Markovic, Danijela, Vatish, Manu, Gu, Mei, Slater, Donna, Newton, Rob, Lehnert, Hendrik and Grammatopoulos, Dimitris (2007) The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium : putative role of interleukin-1ß. Endocrinology, Vol.148 (No.7). pp. 3205-3213. doi:10.1210/en.2007-0095

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Abstract

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-R1ß variant during labor and increased mRNA levels of CRH-R1d mRNA. Studies in myometrial cells identified IL-1ß as an important regulator of myometrial CRH-R1 gene expression because prolonged treatment of myometrial cells with IL-1ß (1 ng/ml) for 18 h induced expression of CRH-R1 mRNA levels by 1.5- to 2-fold but significantly attenuated CRH-R1ß mRNA expression by 70%. In contrast, IL-1ß 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-B mediate IL-1ß 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-1ß 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.

Item Type:	Journal Article
Subjects:	R Medicine > RG Gynecology and obstetrics
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Corticotropin releasing hormone, Myometrium, Labor (Obstetrics) -- Endocrine aspects, Interleukin-1
Journal or Publication Title:	Endocrinology
Publisher:	The Endocrine Society
ISSN:	0013-7227
Official Date:	July 2007
Dates:	Date Event July 2007 Published
Volume:	Vol.148
Number:	No.7
Page Range:	pp. 3205-3213
DOI:	10.1210/en.2007-0095
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Wellcome Trust (London, England), Warwick Private Hospitals Charitable Trust

Data sourced from Thomson Reuters' Web of Knowledge

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