title: The effects of female sexual hormones on the expression and function of α1A- and α1D-adrenoceptor subtypes in the late-pregnant rat myometrium.
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 [(35)S]GTPγS binding of the α1-adrenoceptors, which was most markedly elevated by progesterone. Pertussis toxin inhibited the [(35)S]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.
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary. Electronic address: bota.judit@pharm.u-szeged.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Bóta
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary. Electronic address: judittoth@pharm.u-szeged.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Hajagos-Tóth
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary. Electronic address: ducza@pharm.u-szeged.hu.
authors.forename: Eszter
authors.initials: E
authors.lastname: Ducza
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary. Electronic address: samavati.reza@brc.mta.hu.
authors.forename: Reza
authors.initials: R
authors.lastname: Samavati
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary. Electronic address: borsodi@brc.mta.hu.
authors.forename: Anna
authors.initials: A
authors.lastname: Borsodi
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary. Electronic address: benyhe.sandor@brc.mta.hu.
authors.forename: Sándor
authors.initials: S
authors.lastname: Benyhe
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary. Electronic address: gaspar@pharm.u-szeged.hu.
authors.forename: Róbert
authors.initials: R
authors.lastname: Gáspár
mesh_terms: D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004146:Dioxanes; D010879:Piperazines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011374:Progesterone; D004958:Estradiol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378
keywords: 17β-estradiol; Myometrial contractility; Progesterone; α(1)-adrenoreceptor subtypes