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10:36
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Membrane oestrogen receptor alpha signalling to cell functions.
1Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, Long Beach, CA 90822, USA. ellis.levin@med.va.gov
The Journal of Physiology
|August 19, 2009
Summary
Steroid hormones, like estrogen, activate cellular functions through membrane receptors, not just inside the nucleus. This rapid signaling pathway is conserved across species, impacting diverse biological actions.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Steroid hormone action is traditionally associated with nuclear receptors.
- Non-genomic, extranuclear steroid hormone signaling is conserved from plants to humans.
- Membrane receptors initiate rapid cellular responses to steroid hormones.
Purpose of the Study:
- To review the conserved mechanisms of non-genomic steroid hormone action.
- To highlight the role of membrane-localized steroid receptors.
- To discuss the signaling pathways activated by membrane-bound steroid receptors.
Main Methods:
- Literature review of studies on steroid hormone signaling.
- Focus on membrane-localized estrogen receptor alpha (mERα).
- Comparison of conserved signaling elements across different steroid hormone receptors.
Main Results:
- Steroid hormones (e.g., brassinosteroids, sex steroids) bind to membrane receptors (e.g., tyrosine kinase receptors).
- Membrane receptor ligation triggers rapid signaling cascades involving G proteins, calcium, cAMP, and kinases.
- Evidence supports membrane receptors for glucocorticoids, mineralocorticoids, thyroid hormone, and vitamin D.
Conclusions:
- Extranuclear steroid hormone action is a fundamental biological process.
- Membrane receptors mediate rapid steroid hormone effects crucial for cellular functions.
- Further research is needed to clarify the nature and function of all membrane-localized steroid receptors, including those in mitochondria.
Related Concept Videos
01:31Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
01:31Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
01:07Types of Receptors: Internal Receptors
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
01:21Cell-surface Signaling
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
01:45Endocrine Signaling
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
01:45Endocrine Signaling
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.