MON-254 - The Agonist G-1 Stimulates GPR30, Promoting Hair Growth in Mice via Wnt/Hedgehog Signaling

GPR30 is a membrane-associated receptor that mediates rapid, non-genomic estrogen signaling. Estrogen plays a critical role in hair growth and susceptibility to hair loss through hormonal regulation. Although estrogen has been associated with controlling hair follicle cycling, the underlying molecular mechanisms are not fully understood. In this study, we investigated the role of GPR30 in hair follicle biology and assessed its potential as a therapeutic target for estrogen-mediated hair loss. Using the GPR30-selective agonist G-1, we evaluated the effects of GPR30 activation on hair growth and molecular signaling in female Gpr30-deficient mice with a C57BL/6J background, as well as in human hair follicle dermal papilla cells. Our findings revealed that GPR30 is abundantly expressed in mouse skin, particularly during the anagen phase of the hair follicle cycle. This suggests that GPR30 plays a role in regulating hair growth. Activation of GPR30 by G-1 significantly enhanced the Wnt and Hedgehog signaling pathways in both mouse skin and human dermal papilla cells. These pathways are known to promote hair growth. Importantly, these effects were absent in Gpr30-deficient mice or in the presence of a GPR30 antagonist, confirming the essential role of GPR30 in the estrogen-mediated regulation of hair follicle activity. Taken together, these results identify GPR30 as a critical regulator of hair growth and imply that targeting GPR30 with selective agonists could be an effective treatment for hair loss disorders and other estrogen-responsive conditions.

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