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This version published online on December 7, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-0233
A more recent version of this article appeared on March 1, 2005
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Submitted on February 9, 2004
Accepted on November 23, 2004

{beta}3-adrenoceptor is the predominant {beta}-adrenoceptor subtype in human myometrium and its expression is up regulated in pregnancy

C. Rouget*, M. Bardou, M. Breuiller-Fouché, C. Loustalot, H. Qi, E. Naline, T. Croci, D. Cabrol, C. Advenier, and M. J. Leroy

UPRES EA220 - Pharmacology, UFR Biomédicale des Saints Pères, 45 rue des Saints Pères 75006 Paris France; INSERM U427 and Department of Gynecology, Port-Royal Maternity Hospital, 123 Bd de Port Royal, 75014 Paris France; Department of Gynecology, CHU du Bocage, 21 Bd de Lattre de Tassigny, BP 1542, 21000 Dijon France; Sanofi-Aventis Research Center, Via Piranesi, 38. 20137 Milan Italy; Laboratory of Cardiovascular Physiopathology and Pharmacology, Faculty of Medicine, 7, Bd Jeanne d'Arc, BP 87900, 21079 Dijon France

* To whom correspondence should be addressed. E-mail: celine.rouget{at}univ-paris5.fr.

In order to assess whether pregnancy might influence the functionality and the expression of human myometrial {beta}2- and {beta}3-adrenoceptors ({beta}2- and {beta}3-AR), we performed functional, binding, Western blot and molecular biology experiments in human non-pregnant and near-term pregnant myometrium. Inhibition of spontaneous contractions induced by a {beta}3-AR agonist, SR 59119A, was significantly greater in pregnant compared with non-pregnant myometrial strips (E'max = 61 ± 5% vs. 44 ± 5% for pregnant and non-pregnant myometrium respectively) whereas salbutamol, a {beta}2-AR agonist, was significantly less efficient in pregnant compared with non-pregnant myometrium (Emax = 29 ± 4% vs. 54 ± 8%). Although two populations of binding sites corresponding to {beta}2- and {beta}3-AR were identified in both non-pregnant and pregnant myometrium, we found a clear predominance of the {beta}3-AR subtype. Moreover, {beta}3-AR binding sites were up-regulated 2-fold in myometrium at the end of pregnancy. Both {beta}2- and {beta}3-AR mRNA were expressed in human non-pregnant and pregnant myometrium. Contrary to {beta}2-AR, the expression of the {beta}3-AR transcripts and immunoreactive proteins were increased in pregnant compared with non-pregnant myometrium. Such compelling data suggest a predominant role for {beta}3-AR in the regulation of human myometrium contractility, especially at the end of pregnancy, which might have important consequences for the clinical management of preterm labor.


Key words: {beta}2- and {beta}3-adrenoceptors • pregnancy • human myometrium • mRNA • binding experiments • western blotting analysis




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