By fusion between murine thymoma lines which are either homozygous (r+/r+ or r-/r-) or hemizygous (r+/r-) for the glucocorticoid receptor structural gene r, hybrid clones have been obtained which carry one, two three, or four copies of the r+ allele. These hybrids contain different amounts of normal glucocorticoid receptor as the result of a r+ gene dosage effect. Measurements of the cytolytic ...

Human lymphoblastic leukemia cells of line CEM-C7 are glucocroticoid-sensitive and contain glucocorticoid receptors of wild-type characteristics. EL4 mouse lymphoma cells are resistant to lysis by glucocorticoids due to mutant receptors that exhibit abnormal DNA binding. Hybrids between the two cell lines were prepared and analyzed with respect to glucocorticoid responsiveness and to receptor t...

Highly purified alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] from calf intestine inactivates the glucocorticoid-binding capacity of soluble preparations from mouse fibroblasts (L cells) and rat liver. The unbound receptor is sensitive to inactivation whereas the steroid-bound receptor is unaffected. The ability of the enzyme preparation to ina...

The SAK cell line, derived from a spontaneous thymic lymphoma in an AKR mouse, is resistant to lysis by glucocorticoids in spite of the presence of functional glucocorticoicl receptor. Receptor function was determined by hormone binding analyses, as well as characterization of hormonal effects on cell growth and on the accumulation of murine leukemia virus and metallothionein mRNAs. SAK cells w...

The effects of acetylation on gene expression are complex, with changes in chromatin accessibility intermingled with direct effects on transcriptional regulators. For the nuclear receptors, both positive and negative effects of acetylation on specific gene transcription have been observed. We report that p300 and steroid receptor coactivator 1 interact transiently with the glucocorticoid recept...

Hypocortisolism is a frequent finding in individuals with chronic fatigue syndrome (CFS) with other research findings implying potential dysregulation of glucocorticoid signaling. Glucocorticoid signaling is under the influence of several pathways, several of which are of interest in the study of CFS. Oxidative stress and decreased antioxidant capacity are known to disrupt the hypothalamic-pitu...

The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistan...

A 29-year-old woman with moderately elevated blood pressure and signs of hyperandrogenism (hirsutism and acne) but without typical Cushing's syndrome symptoms has been followed for almost 6 years. Steroid and glucocorticoid receptor studies indicated a primary glucocorticoid receptor defect. Elevated androgen values were of special interest. Clinical manifestation of hyperandrogenism seemed not...