ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1570922
This article is part of the Research TopicWomen in Experimental Pharmacology and Drug Discovery Pharmacology 2025View all articles
The GPR30 Agonist G-1 Promotes Hair Growth via Wnt/Hedgehog Signaling in Mice
Provisionally accepted
- 1Kyoto University, Kyoto, Japan
- 2Kindai University, Higashi-osaka, Ōsaka, Japan
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Background: GPR30 is a membrane-associated receptor involved in rapid, non-genomic estrogen signaling. Estrogen significantly influences hair growth and susceptibility to hair loss, with differences primarily driven by hormonal factors. While estrogen's role in regulating hair follicle cycling is recognized, its precise molecular mechanisms remain unclear. This study investigates the role of GPR30 in hair follicle biology and evaluates its potential as a therapeutic target for estrogenmediated hair loss disorders.The GPR30 selective agonist G-1 was administrated to female Gpr30-deficient mice with a C57BL/6J background and human hair follicle dermal papilla cell, and the effects on hair growth and the molecular signaling were evaluated.We demonstrate that GPR30 is abundantly expressed in mouse skin, particularly during the anagen phase of the hair follicle cycle, implicating it in hair growth regulation. Activation of GPR30 using the selective agonist G-1 in mouse skin and human dermal papilla cells significantly upregulated Wnt/Hedgehog signaling, which are key pathways promoting hair growth. These effects were absent in Gpr30-deficient mice or in those administered a GPR30 antagonist, confirming the essential role of GPR30 in estrogen-mediated regulation of hair follicle activity.Our findings underscore the importance of GPR30 in modulating hair growth and suggest that GPR30, along with its selective agonists, holds promise as a novel therapeutic target for treating hair loss disorders and other estrogen-responsive conditions.
Keywords: GPR30, estrogen, Hair growth, G-1, Wnt/Hedgehog signaling
Received: 04 Feb 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Mayu, Yamanaka, Nishikawa, Masujima, Ohue-Kitano and Kimura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ryuji Ohue-Kitano, Kindai University, Higashi-osaka, 577-8502, Ōsaka, Japan
Ikuo Kimura, Kyoto University, Kyoto, Japan
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