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Transcriptional regulation of steroid receptor coactivator-1 (SRC-1) in glucocorticoid action

I Kurihara1, H Shibata, T Suzuki

  • 1Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

Endocrine Research
|February 24, 2001
PubMed

Insights

Glucocorticoids downregulate steroid receptor coactivator-1 (SRC-1) expression in various rat tissues and cells. This ligand-mediated downregulation of SRC-1 is crucial for regulating glucocorticoid action and protecting cells.

Area of Science:

  • Molecular Endocrinology
  • Gene Regulation
  • Steroid Hormone Action

Background:

  • Steroid receptor coactivators, like SRC-1, enhance transcriptional activity.
  • Glucocorticoid receptor (GR) expression is autoregulated by its ligand.
  • The regulation of coactivator expression by glucocorticoids remains largely unexplored.

Purpose of the Study:

  • To investigate whether glucocorticoids regulate coactivator expression levels.
  • To determine the effect of dexamethasone on SRC-1 mRNA and protein levels.

Main Methods:

  • In vivo studies in various rat tissues (liver, heart, kidney, stomach, cerebrum).
  • In vitro studies using rat renal mesangial cells.
  • Quantitative analysis of SRC-1 mRNA and protein expression following dexamethasone treatment.

Main Results:

  • Dexamethasone treatment significantly downregulated SRC-1 mRNA levels in multiple rat tissues.
  • Dexamethasone also reduced SRC-1 mRNA and protein levels in rat renal mesangial cells.
  • These findings indicate a ligand-mediated downregulation of SRC-1.

Conclusions:

  • Glucocorticoids regulate the expression of coactivators, specifically SRC-1.
  • Ligand-mediated downregulation of SRC-1 plays a critical role in glucocorticoid physiology.
  • This regulatory mechanism may protect cells from excessive glucocorticoid effects.

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