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Minireview: estrogen receptor-mediated rapid signaling
K Moriarty1, K H Kim, J R Bender
1Sections of Cardiovascular Medicine and Immunobiology, Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA.
Endocrinology
|September 2, 2006
Summary
Estrogen receptors (ERs) trigger rapid cell signaling via the cell membrane, distinct from nuclear actions. Understanding these membrane ER pathways and their variants offers insights into hormone replacement therapy.
Area of Science:
- Molecular Endocrinology
- Cell Signaling
- Receptor Biology
Background:
- Estrogen receptors (ERs) mediate both nuclear (genomic) and rapid membrane-initiated (non-genomic) signaling.
- Membrane ER signaling involves multimolecular complexes that activate enzymatic pathways.
- These pathways exhibit cell-type specificity and influence tissue-specific physiological outcomes.
Purpose of the Study:
- To review the evidence supporting the existence and function of membrane-associated estrogen receptors.
- To elucidate the molecular components and signaling pathways involved in membrane-initiated estrogen responses.
- To discuss the role of ER splice variants and tissue-specific ER actions.
Main Methods:
- Literature review synthesizing evidence for membrane ERs and their associated signaling complexes.
- Analysis of molecular mechanisms underlying ligand-activated signal transduction at the plasma membrane.
- Examination of studies detailing ER splice variants and their impact on membrane signaling.
Main Results:
- Established evidence for rapid, membrane-initiated estrogen signaling cascades mediated by plasma membrane-associated ERs.
- Identified the assembly of membrane ER-centered multimolecular complexes as crucial for signal transduction.
- Highlighted cell-type-specific and tissue-specific physiological outcomes of membrane ER signaling, including cross-talk with nuclear responses.
Conclusions:
- Membrane-initiated estrogen responses represent a significant signaling mechanism distinct from genomic pathways.
- Understanding the molecular basis of membrane ERs and their splice variants is key to deciphering complex estrogen actions.
- This knowledge provides critical insights into ongoing controversies regarding hormone replacement therapy in postmenopausal women.
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