Glucocorticoid action and novel mechanisms of steroid resistance: role of glucocorticoid receptor-interacting proteins for glucocorticoid responsiveness

J Endocrinol. 2003 Sep;178(3):331-7. doi: 10.1677/joe.0.1780331.

Abstract

Glucocorticoids are widely used to treat inflammatory and malignant diseases. However, many individuals show a lack of therapeutic response and unwanted side-effects. Various known and unknown parameters determine glucocorticoid responsiveness, among them glucocorticoid receptor (GR)-interacting proteins. Several of the proteins interacting with GR also participate in other signal transduction pathways such as the AP-1 pathway and the nuclear factor-kappaB pathway. We suggest that a closer study of GR-interacting proteins may shed new light on mechanisms determining glucocorticoid sensitivity. In this commentary, the general mechanisms of GR action will be addressed and a proteomic-based method to study GR-interacting proteins will be described in brief.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytosol / metabolism
  • Drug Resistance
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Isoelectric Focusing
  • Liver / metabolism
  • MAP Kinase Signaling System / physiology
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Rats
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Signal Transduction / physiology*
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • 14-3-3 Proteins
  • Anti-Inflammatory Agents
  • NF-kappa B
  • Receptors, Glucocorticoid
  • Tyrosine 3-Monooxygenase
  • Proto-Oncogene Proteins c-raf