Membrane estrogen receptor
Membrane estrogen receptors (mERs) are a group of
Nuclear estrogen receptors such as
Structure-function relationship
In mice and humans, ERβ localization in the plasma membrane occurs after palmitoylation on cysteine 418.[10] Dimerization of mERs appears necessary for their function in rapid cell signaling.[11]
Signaling mechanisms
G-protein coupled receptors
Various electrophysiological studies support E2 signaling via GPCRs.[12][13][14] mERs are thought to activate G-protein coupled receptors to regulate L-type Ca2+ channels and activate protein kinase A (PKA), protein kinase C (PKC), and mitogen activated protein kinase (MAPK) signaling cascades.[15][16]
Gq-coupled mERs (Gq-mERs) activation has been demonstrated to rapidly increase membrane excitability various neuronal cell types by desensitizing
mGluRs
Localization of mERs in caveolae allows them to be held in close proximity to specific receptors such as mGluRs.[20] Various studies have demonstrated mER's ability to activate mGluR signaling, even in the absence of glutamate.[21][22][23] ER/mGluR signaling is thought to be highly relevant for female motivational behavior. Interestingly, modification of caveolin expression appears to alter the nature of ER-mGluR interactions.[24]
Clinical significance
Membrane estrogen receptors have been implicated in reproductive, cardiovascular, neural, and immune function, including cancer, neurodegenerative disease, and cardiovascular disorders.[25][26]
Cancer
GPER1 pathways modify local inflammation and strengthen cellular immune responses in breast cancer and melanoma, making it a strong prognostic marker.[27][28][29]
Neurodegenerative disease
mERs have a demonstrated neuroprotective effect against neurodegenerative disorders like Parkinson's disease, which is thought to underlie the lower incidence of the disorder in women compared to men.[30][31]
Cardiovascular disorders
mERβ has been demonstrated to mitigate cardiac cell pathology caused by angiotensin II.[10][32] Activation of mER but not nuclear ER signaling in vascular epithelial cells promotes protection against vascular injury in mice. Striatin, a scaffolding protein that links mERs to membrane caveolae, is necessary for this effect.[33]
Addiction
Propensity to addiction appears to be mediated by sex hormones such as estrogen.[34] In neural reward circuity, nuclear ERs are not commonly expressed, and mERs have been demonstrated to act on mGluR5 to facilitate psychostimulant-induced behavioral and neurochemical effects.[35][36]
See also
References
- PMID 23756388.
- PMID 22538318.
- ^ PMID 18670908.
- PMID 9973260.
- PMID 12588983.
- PMID 19783454.
- PMID 22538318.
- PMID 20947496.
- S2CID 42396301.
- ^ PMID 36461668.
- PMID 15231873.
- PMID 9106625.
- PMID 9503335.
- PMID 14573532.
- PMID 11578956.)
{{cite journal}}: CS1 maint: multiple names: authors list (link - S2CID 5058096.
- PMID 23820624.
- S2CID 21184175.
- PMID 19549588.
- PMID 28962849.
- PMID 18670908.
- S2CID 16737794.
- PMID 22681685.
- S2CID 17262672.
- PMID 16511588.
- S2CID 42396301.
- PMID 19902352.
- PMID 29336307.
- S2CID 11394158.
- S2CID 202043731.
- PMID 31282427.
- S2CID 263607262.
- PMID 20577045.
- S2CID 45385549.
- PMID 24893316.
- PMID 29195840.