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Cell surface estrogen receptors coupled to cNOS mediate immune and vascular tissue regulation: therapeutic
1Neuroscience Research Institute, State University of New York Old Westbury, Old Westbury, NY 11568, USA. gstefano@li.net
Abstract:
The vast number of reports dealing with estrogen and its associated molecular signaling cascades deal with genomic processes. However, recently data is emerging that demonstrates that estrogen may also work via estrogen cell surface receptors. In this regard, we describe such receptors on human monocytes, granulocytes and vascular endothelial cells. It would appear that these receptors are coupled to constitutive nitric oxide synthase derived nitric oxide release via the stimulation of intracellular calcium transients. It is this cascade that has the ability to down regulate both immune and vascular cellular processes, i. e, adherence. Based on this, for example we surmise that in menopause an earlier initiation of estrogen therapy may be more beneficial so as to prevent a decrease in its cellular signaling and maintenance functions, at least with respect to NO-related events.
Insights
Estrogen acts via cell surface receptors to regulate immune and vascular functions through nitric oxide signaling. Early estrogen therapy may preserve these crucial cellular processes, particularly during menopause.
Area of Science:
- Endocrinology
- Molecular Biology
- Immunology
Background:
- Estrogen's genomic signaling is well-established.
- Emerging evidence suggests non-genomic, cell surface receptor-mediated actions of estrogen.
Purpose of the Study:
- To investigate estrogen cell surface receptors on human immune and vascular cells.
- To elucidate the signaling cascade involving nitric oxide release.
Main Methods:
- Identification of estrogen cell surface receptors on monocytes, granulocytes, and vascular endothelial cells.
- Analysis of intracellular calcium transients and nitric oxide release.
Main Results:
- Estrogen cell surface receptors were identified on target cells.
- Receptor activation stimulates nitric oxide release via intracellular calcium signaling.
- This cascade down-regulates immune and vascular cellular adherence.
Conclusions:
- Estrogen exerts rapid, non-genomic effects through cell surface receptors.
- Estrogen signaling impacts immune and vascular cell function via nitric oxide.
- Early estrogen therapy may be beneficial in menopause to maintain cellular functions.