Elsevier

Steroids

Volume 56, Issue 2, February 1991, Pages 52-58
Steroids

Autoregulation of glucocorticoid receptor gene expression

https://doi.org/10.1016/0039-128X(91)90124-EGet rights and content

Abstract

Glucocorticoid receptors are members of a highly conserved family of steroid receptor proteins, which are ligand-dependent transcription factors. Previous studies have shown that the presence of functional glucocorticoid receptors is a prerequisite for manifestation of cellular responses to hormone. Glucocorticoid receptors undergo down-regulation following treatment with glucocorticoids. To define the molecular mechanisms that are involved in this process we have analyzed the down-regulation of glucocorticoid receptors both in HeLa cells, which contain endogenous receptors, and in cells containing receptors that have been introduced by DNA transfection. Our results show that cells that contain glucocorticoid receptors—either endogenous or transfected—undergo down-regulation of steroid-binding capabilities, as well as reductions in receptor protein and mRNA levels, in a remarkably similar fashion. DNA sequences in the coding region of the human glucocorticoid receptor cDNA appear to be sufficient to account for down-regulation of receptor. This novel finding suggests that unique mechanisms are involved in controlling glucocorticoid receptor homeostasis.

References (46)

  • KL Burnstein et al.

    Human glucocorticoid receptor cDNA contains sequences sufficient for receptor down regulation

    J Biol Chem

    (1990)
  • JE Kalinyak et al.

    Tissue-specific regulation of glucocorticoid receptor mRNA by dexamethasone

    J Biol Chem

    (1987)
  • S Rosewicz et al.

    Mechanism of glucocorticoid receptor down regulation by glucocorticoids

    J Biol Chem

    (1988)
  • W Hoeck et al.

    Down-regulation and phosphorylation of glucocorticoid receptors in cultured cells: investigations with a monospecific antiserum against a bacterially expressed receptorfragment

    J Biol Chem

    (1989)
  • WR McIntyre et al.

    Triamcinolone acetonide regulates glucocorticoid receptor levels by decreasing the halflife of the activated nuclear receptor form

    J Biol Chem

    (1985)
  • CW Distelhorst et al.

    Kinetic pulse chase labeling study of the glucocorticoid receptor in mouse lymphoma cells: effect of glucocorticoid and antiglucocorticoid hormones onintracellularreceptorhalf life

    J Biol Chem

    (1989)
  • A Munck et al.

    Glucocorticoid receptors and mechanisms of action

  • ER Sanchez et al.

    Demonstration that the 90-kilodalton heat shock protein is bound to the glucocorticoid receptor in its 9S nondeoxynucleic acid binding form

    Mol Endocrinol

    (1987)
  • WV Vedeckis

    Subunit dissociation as a possible mechanism of glucocorticoid receptor activation

    Biochemistry

    (1983)
  • KR Yamamoto

    Steroid receptor regulated transcription of specific genes and gene networks

    Annu Rev Genet

    (1985)
  • KL Burnstein et al.

    Regulation of gene expression by glucocorticoids

    Annu Rev Physiol

    (1989)
  • DD Petersen et al.

    3' Noncoding region of phosphoenolpyruvate carboxykinase mRNA contains a glucocorticoid-responsive mRNA stabilizing element

  • S Bourgeois et al.

    Correlation between glucocorticoid receptor and cytolytic response of murine lymphoid cell lines

    Cancer Res

    (1979)
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