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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Intercommunication between Voltage-Gated Calcium Channels and Estrogen Receptor/Estrogen Signaling: Insights into
Yashashwini Dinesh Subbamanda1, Anamika Bhargava1
1Department of Biotechnology, Indian Institute of Technology Hyderabad (IITH), Kandi, Sangareddy 502284, Telangana, India.
Abstract:
Voltage-gated calcium channels (VGCCs) and estrogen receptors are important cellular proteins that have been shown to interact with each other across varied cells and tissues. Estrogen hormone, the ligand for estrogen receptors, can also exert its effects independent of estrogen receptors that collectively constitute non-genomic mechanisms. Here, we provide insights into the VGCC regulation by estrogen and the possible mechanisms involved therein across several cell types. Notably, most of the interaction is described in neuronal and cardiovascular tissues given the importance of VGCCs in these electrically excitable tissues. We describe the modulation of various VGCCs by estrogen known so far in physiological conditions and pathological conditions. We observed that in most in vitro studies higher concentrations of estrogen were used while a handful of in vivo studies used meager concentrations resulting in inhibition or upregulation of VGCCs, respectively. There is a need for more relevant physiological assays to study the regulation of VGCCs by estrogen. Additionally, other interacting receptors and partners need to be identified that may be involved in exerting estrogen receptor-independent effects of estrogen.
Insights
Estrogen regulates voltage-gated calcium channels (VGCCs) through genomic and non-genomic mechanisms. Research highlights varied effects based on estrogen concentration and cell type, necessitating further physiological studies.
Area of Science:
- Molecular Biology
- Neuroscience
- Endocrinology
Background:
- Voltage-gated calcium channels (VGCCs) and estrogen receptors are key cellular proteins with known interactions.
- Estrogen exerts effects both via estrogen receptors and independently through non-genomic pathways.
Purpose of the Study:
- To elucidate the mechanisms of VGCC regulation by estrogen across various cell types.
- To review known modulations of VGCCs by estrogen under physiological and pathological conditions.
Main Methods:
- Literature review of in vitro and in vivo studies examining estrogen-VGCC interactions.
- Analysis of estrogen concentrations used in different study designs.
Main Results:
- Estrogen's regulation of VGCCs varies, with higher in vitro concentrations often causing inhibition and lower in vivo concentrations leading to upregulation.
- Interactions are most studied in neuronal and cardiovascular tissues.
Conclusions:
- Further research with physiologically relevant assays is needed to understand estrogen's regulation of VGCCs.
- Identifying novel interacting partners is crucial for understanding estrogen's receptor-independent effects.
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