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The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium : putative role of interleukin-1ß

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Markovic, Danijela, Vatish, Manu, Gu, Mei, Slater, Donna, Newton, Rob, Lehnert, Hendrik and Grammatopoulos, Dimitris K.. (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. ISSN 0013-7227

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Official URL: http://dx.doi.org/10.1210/en.2007-0095

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

Identification Number:

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

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