Treatment of rat liver cytosol with hydrogen peroxide (H2O2) or sodium molybdate (MoO4(2-)) inhibits thermal inactivation of glucocorticoid receptor steroid-binding capacity at 25 degrees C. Dithiothreitol (DTT) prevents the stabilization of receptors by H2O2. Heating (25 degrees C) of immune pellets formed by immunoadsorption of L-cell murine glucocorticoid receptor complexes to protein-A-Seph...

Early experience permanently alters behavior and physiology. These effects are, in part, mediated by sustained alterations in gene expression in selected brain regions. The critical question concerns the mechanism of these environmental "programming" effects. We examine this issue with an animal model that studies the consequences of variations in mother-infant interactions on the development o...

Postnatal handling increases glucocorticoid receptor expression in the rat hippocampus, thus altering the regulation of hypothalamic synthesis of corticotropin-releasing hormone and the hypothalamic-pituitary-adrenal response to stress. The effect on glucocorticoid receptor gene expression represents one mechanism by which the early environment can exert a long-term effect on neural development...

The Mr 94,000 steroid binding component of rat hepatic glucocorticoid receptor purified 5000-fold under-goes calcium-stimulated phosphorylation in vitro by [gamma-32P]ATP. Exogenous histones can be phosphorylated by this preparation without calcium. Calmodulin did not stimulate phosphorylation of the glucocorticoid receptor beyond that obtained with calcium alone. Although the specific calmodul...

The antimalaria drug chloroquine has been used as an anti-inflammatory agent for treating systemic lupus erythematosus and rheumatoid arthritis. We report that chloroquine promoted the transrepression of proinflammatory cytokines by the glucocorticoid receptor (GR). In a mouse collagen-induced arthritis model, chloroquine enhanced the therapeutic effects of glucocorticoid treatment. By inhibiti...

The feedback regulation of the human glucocorticoid receptor gene by glucocorticoid receptor-hormone complexes involves the recruitment of the nuclear phosphatase, PP2A. The PP2A holoenzyme consists of a structural subunit A, a catalytic subunit C, and a variable regulatory subunit B or PPP2R3C,with distinct specificities. Our goal was to investigate the nature of the interaction between glucoc...

Hepatic glucocorticoid receptor binding activity was measured in A/J, C57BL/6J, their F1 reciprocal crosses and their F1 recombinant inbred (RI) lines. The glucocorticoid binding capacity was measured in Hepes buffer and Hepes buffer plus dithiothreitol (DTT). The A/J parental strain showed higher levels, and a greater increase of glucocorticoid binding in the presence of DTT, than did the C57B...

We have recently purified the modulator of the glucocorticoid-receptor complex from rat liver. Purified modulator inhibits glucocorticoid-receptor complex activation and stabilizes the steroid-binding ability of the unoccupied glucocorticoid receptor. Since these activities are shared by exogenous sodium molybdate, modulator appears to be the endogenous factor that sodium molybdate mimics. In t...

Steroid hormone receptors and Stat factors comprise two distinct families of inducible transcription factors. Activation of a member of each family, namely the glucocorticoid receptor by glucocorticoids and Stat5 by prolactin, is required for the efficient induction of the expression of milk protein genes in the mammary epithelium. We have studied the mode of interaction between Stat5 and the g...

Glucocorticoids increase the number of insulin receptors in cultured human lymphocytes. This effect is specific for the insulin receptor as growth hormone receptor concentration decreases. The effect is time-dependent, dose-dependent over the physiologic concentration range of glucocorticoid, reversible, and appears to be mediated via specific glucocorticoid receptors. Protein synthesis and gly...