In Vivo Effects of a GPR30 Antagonist

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2009 May 12

PMID 19430488

Citations 241

Authors

Megan K Dennis

Ritwik Burai

Chinnasamy Ramesh

Whitney K Petrie

Sara N Alcon

Tapan K Nayak

Cristian G Bologa

Andrei Leitao

Eugen Brailoiu

Elena Deliu

Nae J Dun

Larry A Sklar

Helen J Hathaway

Jeffrey B Arterburn

Tudor I Oprea

Eric R Prossnitz

Affiliations

Soon will be listed here.

Abstract

Estrogen is central to many physiological processes throughout the human body. We have previously shown that the G protein-coupled receptor GPR30 (also known as GPER), in addition to classical nuclear estrogen receptors (ER and ER), activates cellular signaling pathways in response to estrogen. In order to distinguish between the actions of classical estrogen receptors and GPR30, we have previously characterized G-1 (1), a selective agonist of GPR30. To complement the pharmacological properties of G-1, we sought to identify an antagonist of GPR30 that displays similar selectivity against the classical estrogen receptors. Here we describe the identification and characterization of G15 (2), a G-1 analog that binds to GPR30 with high affinity and acts as an antagonist of estrogen signaling through GPR30. In vivo administration of G15 revealed that GPR30 contributes to both uterine and neurological responses initiated by estrogen. The identification of this antagonist will accelerate the evaluation of the roles of GPR30 in human physiology.

Citing Articles

Interaction of GPER-1 with the endocrine signaling axis in breast cancer.

Molina Calistro L, Arancibia Y, Olivera M, Domke S, Torres R Front Endocrinol (Lausanne). 2025; 16:1494411.

PMID: 39936103 PMC: 11811623. DOI: 10.3389/fendo.2025.1494411.

GPER1 signaling restricts macrophage proliferation and accumulation in human hepatocellular carcinoma.

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PMID: 39582864 PMC: 11582010. DOI: 10.3389/fimmu.2024.1481972.

GPR30 Selective Agonist G1 Exhibits Antiobesity Effects and Promotes Insulin Resistance and Gluconeogenesis in Postmenopausal Mice Fed a High-Fat Diet.

Liu D, Zheng M, Lu C, Miao M, Zhan Y, Ma F J Lipids. 2024; 2024:5513473.

PMID: 39554996 PMC: 11567725. DOI: 10.1155/2024/5513473.

Activation of G Protein-Coupled Estrogen Receptor 1 (GPER) Attenuates Obesity-Induced Asthma by Switching M1 Macrophages to M2 Macrophages.

Son S, Im D Int J Mol Sci. 2024; 25(17).

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G protein-coupled estrogen receptor 1 and collagen XVII endodomain expression in human cutaneous melanomas: can they serve as prognostic factors?.

Cakir U, Balogh P, Ferenczik A, Brodszky V, Krenacs T, Karpati S Pathol Oncol Res. 2024; 30:1611809.

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