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ß₃-Adrenoceptor Is the Predominant ß-Adrenoceptor Subtype in Human Myometrium and Its Expression Is Up-Regulated in Pregnancy

Unité Propre de Recherche de l’Enseignement Supérieur EA220–Pharmacology (C.R., M.B., H.Q., E.N., C.A.), Unité de Formation et de Recherche Biomédicale des Saints Pères, 75006 Paris, France; Institut National de la Santé et de la Recherche Médicale U427 (C.R., M.B.-F., H.Q., D.C., M.J.L.) and Department of Gynecology (D.C.), Port-Royal Maternity Hospital, 75014 Paris, France; Department of Gynecology (C.L.), Centre Hospitalier Universitaire du Bocage, 21000 Dijon, France; Sanofi-Aventis Research Center (T.C.), 20137 Milan, Italy; Laboratory of Cardiovascular Physiopathology and Pharmacology (M.B.), Faculty of Medicine, 21079 Dijon, France

Address all correspondence and requests for reprints to: Céline Rouget, Unité Propre de Recherche de l’Enseignement Supérieur EA220–Pharmacology, Unité de Formation et de Recherche Biomédicale des Saints Pères, 45 rue des Saints Pères, F-75006 Paris, France. E-mail: celine.rouget{at}univ-paris5.fr.

To assess whether pregnancy might influence the functionality and expression of human myometrial ß₂- and ß₃-adrenoceptors (ß₂- and ß₃-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 ß₃-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 ß₂-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 ß₂- and ß₃-AR were identified in both nonpregnant and pregnant myometrium, we found a clear predominance of the ß₃-AR subtype. Moreover, ß₃-AR binding sites were up-regulated 2-fold in myometrium at the end of pregnancy. Both ß₂- and ß₃-AR mRNA were expressed in human nonpregnant and pregnant myometrium. Contrary to ß₂-AR, the expression of the ß₃-AR transcripts and immunoreactive proteins was increased in pregnant, compared with nonpregnant, myometrium. Such compelling data suggest a predominant role for ß₃-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.

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