Beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in human myometrium and its expression is up-regulated in pregnancy

J Clin Endocrinol Metab. 2005 Mar;90(3):1644-50. doi: 10.1210/jc.2004-0233. Epub 2004 Dec 7.

Abstract

To assess whether pregnancy might influence the functionality and 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 nonpregnant 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 nonpregnant, myometrial strips (E'(max) = 61 +/- 5% vs. 44 +/- 5% for pregnant and nonpregnant myometrium, respectively), whereas salbutamol, a beta(2)-AR agonist, was significantly less efficient in pregnant, compared with nonpregnant, myometrium (E(max) = 29 +/- 4 vs. 54 +/- 8%). Although two populations of binding sites corresponding to beta(2)- and beta(3)-AR were identified in both nonpregnant 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 nonpregnant and pregnant myometrium. Contrary to beta(2)-AR, the expression of the beta(3)-AR transcripts and immunoreactive proteins was increased in pregnant, compared with nonpregnant, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Albuterol / pharmacology
  • Binding Sites / physiology
  • Blotting, Western
  • Ethanolamines / pharmacology
  • Female
  • Gene Expression / physiology
  • Humans
  • Myometrium / physiology*
  • Pregnancy / physiology*
  • RNA, Messenger / analysis
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Adrenergic, beta-3 / genetics*
  • Receptors, Adrenergic, beta-3 / metabolism*
  • Tetrahydronaphthalenes / pharmacology
  • Up-Regulation / physiology
  • Uterine Contraction / drug effects
  • Uterine Contraction / physiology

Substances

  • Adrenergic beta-Agonists
  • Ethanolamines
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • SR 59119A
  • Tetrahydronaphthalenes
  • Albuterol