Effect of adrenal manipulation on glucocorticoid receptors in MM1 hamster melanoma.

Cytosol glucocorticoid receptor of hamster Malignant Melanoma No. 1 (MM1) was characterized by dextran-coated charcoal and sucrose gradient assays. MM1 contains a specific, saturable, high-affinity (Kd 2.5 nM; 73.3 fmol/mg cytosol protein) receptor for glucocorticoid. The receptor sedimented at 7 to 8S in low-salt buffer and 5.5S in 0.4 M KCl and was sensitive to proteolysis by trypsin. Glucocorticoid receptor was inactivated by 40% (NH4)2SO4. Addition of 20 mM molybdate to the homogenizing buffer prevented inactivation. Adrenalectomy increased MM1 receptor content without altering affinity. Chronic exposure of intact or adrenalectomized hamsters to gluco- and high-dose mineralocorticoid significantly decreased the amount of unbound glucocorticoid receptors available for binding. Exposure of intact hamsters to high doses of mineralocorticoid also decreased apparent receptor affinity. These results suggest that hamster MM1 contains a high-affinity cytosol receptor for glucocorticoids similar to that of other glucocorticoid-responsive tissues, which may mediate the action of adrenal steroids on tumor behavior.