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Updated: Jul 11, 2026
10:51
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Extranuclear steroid receptors: nature and actions
Stephen R Hammes1, Ellis R Levin
1Department of Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8857, USA. stephen.hammes@utsouthwestern.edu
Endocrine Reviews
|October 6, 2007
Summary
Steroid hormones rapidly affect cells via membrane receptors, influencing protein modification and gene expression. Understanding these membrane-initiated steroid signaling pathways is crucial for various biological processes and diseases.
Area of Science:
- Molecular Endocrinology
- Cellular Signaling
- Membrane Biology
Background:
- Steroid hormones traditionally exert genomic effects via nuclear receptors.
- Emerging evidence shows rapid, non-genomic effects initiated at the plasma membrane.
Purpose of the Study:
- To review recent advancements in understanding membrane-initiated steroid signaling (MISS).
- To explore the integration of extranuclear and nuclear steroid receptor functions.
Main Methods:
- Review of existing literature on steroid receptor localization and function.
- Analysis of signaling pathways involving membrane receptors, G proteins, and kinases.
- Examination of structural determinants for membrane receptor activity.
Main Results:
- Steroid receptors can function at the plasma membrane, mediating rapid cellular responses.
- MISS involves protein modification, ion flux, and kinase cascades, impacting gene expression.
- Extranuclear and nuclear receptor pools likely comprise the same proteins.
Conclusions:
- Rapid steroid signaling is integral to diverse physiological processes, including reproduction and cardiovascular function.
- Further research is needed to fully elucidate the integration of membrane and nuclear receptor actions in organ biology.
- Understanding MISS is key to advancing fields like cancer biology and endocrinology.
Related Concept Videos
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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...
01:31Internal 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.
01:08Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...