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1 January 2009 GPR30 Does Not Mediate Estrogenic Responses in Reproductive Organs in Mice
Christiane Otto, Iris Fuchs, Gunther Kauselmann, Heidrun Kern, Branko Zevnik, Puk Andreasen, Gilda Schwarz, Helga Altmann, Mario Klewer, Michael Schoor, Richardus Vonk, Karl-Heinrich Fritzemeier
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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.

Christiane Otto, Iris Fuchs, Gunther Kauselmann, Heidrun Kern, Branko Zevnik, Puk Andreasen, Gilda Schwarz, Helga Altmann, Mario Klewer, Michael Schoor, Richardus Vonk, and Karl-Heinrich Fritzemeier "GPR30 Does Not Mediate Estrogenic Responses in Reproductive Organs in Mice," Biology of Reproduction 80(1), 34-41, (1 January 2009). https://doi.org/10.1095/biolreprod.108.071175
Received: 12 June 2008; Accepted: 1 August 2008; Published: 1 January 2009
KEYWORDS
estradiol
estradiol receptor
female reproductive tract
Gpr30-deficient mice
mammary gland
mechanisms of hormone action
reproduction
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