ABSENCE IN GLUCOCORTICOID-RESISTANT MOUSE LYMPHOMA-P1798 OF A GLUCOCORTICOID RECEPTOR DOMAIN RESPONSIBLE FOR BIOLOGICAL EFFECTS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (7) , 3127-3131
Abstract
Glucocorticoid-resistant (CR), in contrast to glucocorticoid-sensitive (CS), mouse lymphoma P1798 lacked anti-glucocorticoid receptor immunoactivity. Antibodies raised against the purified rat liver glucocorticoid receptor (GR) cross-reacted with the GR from CS, but not with the GR from CR, P1798 lymphoma. Using highly specific antisera against the GR in an indirect competitive enzyme-linked immunosorbent assay, .alpha.-chymotrypsin digestion of the GR from CS P1798 lymphoma caused a separation of a resistant-like nonimmunogenic steroid and DNA-binding domain (Stokes'' radius, 3.3 nm) from an immunoactive domain (Stokes'' radius, 2.6 nm). In contrast to CS P1798 lymphoma, immunoactivity could not be found in the cytosol from CR P1798 lymphoma before or after .alpha.-chymotrypsin digestion. This was assayed after chromatography on DNA-cellulose or gel filtration on Agarose A (0.5 m). The domain of the CS GR containing the immunoactive determinant(s), normally removed by limited proteolysis by .alpha.-chymotrypsin, appears to be missing in CR P1798 lymphoma cytosol. This domain may play an important role in the mechanism of action of glucocorticoids. This might suggest that a mutation has occurred affecting the genome resulting in defective transcription of the receptor gene(s) in CR P1798 lymphoma.