β3-adrenoceptor is the predominant β-adrenoceptor subtype in human myometrium and its expression is up-regulated in pregnancy

Abstract

To assess whether pregnancy might influence the functionality and expression of human myometrial β2 and β3- adrenoceptors (β2- and β3-AR), we performed functional, binding, Western blot, and molecular biology experiments in human nonpregnant and near-term pregnant myometrium. Inhibition of spontaneous contractions induced by a β3-AR agonist, SR 59119A, was significantly greater in pregnant, compared with nonpregnant, myometrial strips (E′max = 61 ± 5% vs. 44 ± 5% for pregnant and nonpregnant myometrium, respectively), whereas salbutamol, a β2-AR agonist, was significantly less efficient in pregnant, compared with nonpregnant, myometrium (Emax = 29 ± 4 vs. 54 ± 8%). Although two populations of binding sites corresponding to β2- and β3-AR were identified in both nonpregnant and pregnant myometrium, we found a clear predominance of the β3-AR subtype. Moreover, β3-AR binding sites were up-regulated 2-fold in myometrium at the end of pregnancy. Both β2- and β3-AR mRNA were expressed in human nonpregnant and pregnant myometrium. Contrary to β2-AR, the expression of the β3-AR transcripts and immunoreactive proteins was increased in pregnant, compared with nonpregnant, myometrium. Such compelling data suggest a predominant role for β3-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. Copyright © 2005 by The Endocrine Society.