title: GPR30 does not mediate estrogenic responses in reproductive organs in mice.
abstract: The G protein-coupled receptor Gpr30 (Gper) was recently claimed to bind to estradiol and to activate cytoplasmic signal transduction pathways in response to estradiol. However, there are conflicting data regarding the role of Gpr30 as an estrogen receptor (ER): several laboratories were unable to demonstrate estradiol binding to GPR30 or estradiol-activated signal transduction in Gpr30-expressing cells. To clarify the potential role of Gpr30 as an ER, we generated Gpr30-deficient mice. Although Gpr30 was expressed in all reproductive organs, histopathological analysis did not reveal any abnormalities in these organs in Gpr30-deficient mice. Mutant male and female mice were as fertile as their wild-type littermates, indicating normal function of the hypothalamic-pituitary-gonadal axis. Moreover, we analyzed estrogenic responses in two major estradiol target organs, the uterus and the mammary gland. For that purpose, we examined different readout paradigms such as morphological measures, cellular proliferation, and target gene expression. Our data demonstrate that in vivo Gpr30 is dispensable for the mediation of estradiol effects in reproductive organs. These results are in clear contrast to the phenotype of mice lacking the classic ER alpha (Esr1) or aromatase (Cyp19a1). We conclude that the perception of Gpr30 (based on homology related to peptide receptors) as an ER might be premature and has to be reconsidered.
authors.affiliation: Therapeutic Research Group Women's Healthcare, Bayer Schering Pharma AG, 13353 Berlin, Germany. christiane.otto@bayerhealthcare.com
authors.forename: Christiane
authors.initials: C
authors.lastname: Otto
authors.forename: Iris
authors.initials: I
authors.lastname: Fuchs
authors.forename: Gunther
authors.initials: G
authors.lastname: Kauselmann
authors.forename: Heidrun
authors.initials: H
authors.lastname: Kern
authors.forename: Branko
authors.initials: B
authors.lastname: Zevnik
authors.forename: Puk
authors.initials: P
authors.lastname: Andreasen
authors.forename: Gilda
authors.initials: G
authors.lastname: Schwarz
authors.forename: Helga
authors.initials: H
authors.lastname: Altmann
authors.forename: Mario
authors.initials: M
authors.lastname: Klewer
authors.forename: Michael
authors.initials: M
authors.lastname: Schoor
authors.forename: Richardus
authors.initials: R
authors.lastname: Vonk
authors.forename: Karl-Heinrich
authors.initials: KH
authors.lastname: Fritzemeier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D066246:ErbB Receptors / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D008098:Litter Size / Q000502:physiology; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014599:Uterus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
chemical_list: C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol; D012313:RNA; D066246:ErbB Receptors