title: G-1-activated membrane estrogen receptors mediate increased contractility of the human myometrium.
abstract: Estrogens are key mediators of increased uterine contractility at labor. We sought to determine whether membrane-associated estrogen receptors, such as the recently described seven-transmembrane receptor G protein-coupled receptor 30 (GPR30), mediated some of this effect. Using human myometrium obtained at term cesarean section before or after the onset of labor, we demonstrated the presence of GPR30 mRNA and protein using quantitative RT-PCR and Western blotting. GPR30 receptor was localized to the cell membrane and often colocalized with calveolin-1. Using the specific estrogen membrane receptor agonist G-1 and myometrial explants, we showed that membrane receptor activation led to phosphorylation of MAPK and the actin-modifying small heat shock protein 27. Using myometrial strips incubated with G-1 or vehicle we demonstrated that estrogen membrane receptor activation increased the myometrial contractile response to oxytocin. These data suggest that activation of the plasma membrane estrogen receptor GPR30 likely participates in the physiology of the human myometrium during pregnancy and identifies it as a potential target to modify uterine activity.
authors.affiliation: Mothers & Babies Research Centre/Endocrine Unit, Faculty of Health/School of Medicine & Public Health, The University of Newcastle & John Hunter Hospital, New Soth Wales, Australia. kaushik.maiti@newcastle.edu.au
authors.forename: K
authors.initials: K
authors.lastname: Maiti
authors.forename: J W
authors.initials: JW
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Read
authors.forename: E C
authors.initials: EC
authors.lastname: Chan
authors.forename: S C
authors.initials: SC
authors.lastname: Riley
authors.forename: P
authors.initials: P
authors.lastname: Nahar
authors.forename: R
authors.initials: R
authors.lastname: Smith
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009215:Myometrium / Q000502:physiology*; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D014590:Uterine Contraction / Q000235:genetics / Q000378:metabolism*
chemical_list: D004967:Estrogens; C109584:GPER1 protein, human; D055551:HSP27 Heat-Shock Proteins; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled