The effects of female sexual hormones on the expression and function of α1A- and α1D-adrenoceptor subtypes in the late-pregnant rat myometrium

Bóta, Judit and Hajagos-Tóth, Judit and Ducza, Eszter and Samavati, Reza and Borsodi, Anna and Benyhe, Sándor (2015) The effects of female sexual hormones on the expression and function of α1A- and α1D-adrenoceptor subtypes in the late-pregnant rat myometrium. European Journal of Pharmacology, 769. pp. 177-184. ISSN 0014-2999

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Abstract

The aim of the study was to investigate the roles of α1-adrenoceptor subtypes in the last-day pregnant rat uterus in vitro by the administration of subtype-specific antagonists (the α1A-adrenoceptor antagonist WB 4101 and the α1D-adrenoceptor antagonist BMY 7378) after 17β-estradiol or progesterone pretreatment. In isolated organ bath studies, contractions were elicited with (-)-noradrenaline (10-8-10-5 M) in the presence of propranolol (10-5 M) and yohimbine (10-6 M) in order to avoid β-, and α2-adrenergic action. The myometrial expressions of the α1-adrenoceptor subtypes were determined by means of the real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting techniques. The activated G protein levels were investigated through radiolabelled GTP binding assays. Both 17β-estradiol and progesterone pretreatment changed the myometrial contracting effect of (-)-noradrenaline. In the presence of WB 4101, progesterone pretreatment decreased the (-)-noradrenaline-induced myometrial contraction. In the presence of BMY 7378, both the 17β-estradiol and the progesterone pretreatment reduced the effect of (-)-noradrenaline. The mRNA and protein expressions of the α1A-adrenoceptors were decreased after 17β-estradiol pretreatment. (-)-Noradrenaline increased the [35S]GTPγS binding of the α1-adrenoceptors, which was most markedly elevated by progesterone. Pertussis toxin inhibited the [35S]GTPγS binding-stimulating effect of (-)-noradrenaline, indicating the role of Gi proteins in the signal mechanisms. 17β-estradiol pretreatment blocks the expression of the α1A-adrenoceptors, whereas it does not influence the expression of the α1D-adrenoceptors. Progesterone pretreatment does not have any effect on the myometrial mRNA and protein expressions of the α1-adrenoceptors, but it alters the G protein coupling of these receptors, promoting a Gi-dependent pathway. © 2015 Elsevier B.V. All rights reserved.

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