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AuthorFardoun, Manal
AuthorMondello, Stefania
AuthorKobeissy, Firas
AuthorEid, Ali H.
Available date2023-03-05T07:06:19Z
Publication Date2022-11-10
Publication NameFrontiers in Pharmacology
Identifierhttp://dx.doi.org/10.3389/fphar.2022.1061374
CitationFardoun M, Mondello S, Kobeissy F and Eid AH (2022) G protein estrogen receptor as a potential therapeutic target in Raynaud’s phenomenon. Front. Pharmacol. 13:1061374. doi: 10.3389/fphar.2022.1061374
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85142483910&origin=inward
URIhttp://hdl.handle.net/10576/40623
AbstractExaggerated cold-induced vasoconstriction can precipitate a pathogenesis called Raynaud’s phenomenon (RP). Interestingly, RP is significantly more prevalent in females than age-matched men, highlighting the potential implication of 17β-estradiol (E2) in the etio-pathogenesis of this disease. Indeed, we have previously reported that E2 stimulates the expression of vascular alpha 2C-adrenoceptors (α2C-AR), the sole mediator of cold-induced constriction of cutaneous arterioles. This induced expression occurs through the cyclic adenosine monophosphate → exchange protein activated by cAMP→ Ras-related protein 1→ c-Jun N-terminal kinase→ activator protein-1 (cAMP/Epac/Rap/JNK/AP-1 pathway). On the basis that estrogen-induced rapid cAMP accumulation and JNK activation occurs so rapidly we hypothesized that a non-classic, plasma membrane estrogen receptor was the mediator. We then showed that an impermeable form of E2, namely E2:BSA, mimics E2 effects suggesting a role for the membranous G-protein coupled estrogen receptor (GPER) in E2-induced α2C-AR expression. Our current working hypothesis and unpublished observations further cement this finding, as G1, a GPER agonist, mimics while G15, a GPER antagonist, abrogates estrogen’s effect on the expression of vascular α2C-AR. These, and other observations, highlight the potential of GPER as a tractable target in the management of RP, particularly in pre-menopausal women.
SponsorAPCs for this paper have been offset by a generous support from Frontiers as part of the support offered to women in pharmacology, for the specific invitation to Women in Translational Pharmacology: 2021.
Languageen
PublisherFrontiers Media
Subjectalpha 2C adrenoceptor
cardiovascular disease
estrogen
gender bias
GPER
raynaud’s phenomenon
vasoconstriction
VSMC
TitleG protein estrogen receptor as a potential therapeutic target in Raynaud’s phenomenon
TypeArticle
Volume Number13
ESSN1663-9812
dc.accessType Open Access


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