Steroid Receptor Activation: The Glucocorticoid Receptor as a Model System
The glucocorticoid receptor has been used as a model for steroid receptor activation. Because of recent evidence for the essentially nuclear location of the unoccupied receptors of 1,25-dihydroxycholecalciferol and 17 β-estradiol, the significance of the activation mechanism converting unactivated receptor complexes to DNA-binding forms is unclear for some receptors. Up to now the weight of evidence favors a cytoplasmic location of the unactivated glucocorticoid receptor. In this article we describe studies on the nature of the activation mechanism and of regulatory factors. Activation is defined as the conversion of non-DNA binding forms of steroid-receptor complexes to DNA binding forms. In vivo studies suggest that the activation mechanism has biological significance since it occurs under physiological conditions. The activation mechanism may consist of two steps in vitro, the first of which is sensitive to molybdate. The second step may involve the removal of an RNA from the receptor complex by RNase. Activation also results in a decreased molecular size of the receptor complex. Regulatory factors influencing activation which have been identified so far include a low molecular weight modulator which inhibits activation and a macromolecular inhibitor. A macromolecule in cytosol also acts as a stimulator of the second step of activation and may be RNase. Since phosphorylation/dephosphorylation may play some role in this overall process, the activity of a protein kinase has been described which is associated with the purified, liganded receptor and which mediates the phosphorylation of the 90,000 molecular weight steroid-binding component of the receptor complex. All of these observations are synthesized into a speculative mechanism of action of the glucocorticoid receptor complex and its activation.
KeywordsGlucocorticoid Receptor Receptor Complex Triamcinolone Acetonide Estradiol Receptor Coid Receptor
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