Glucocorticoid receptors in Morris hepatomas and host liver and the correlation of biological activity with receptor levels.
Glucocorticoid-binding macromolecules were examined in Morris hepatomas 7787, 5123tc, 3683F, 7800, and 3683 and the Reuber hepatoma H-35 with the use of the synthetic glucocorticoid, triamcinolone acetonide. The physical properties of the triamcinolone acetonide-binding macromolecules of the hepatomas indicate that they are specific glucocorticoid receptors. The equilibrium association constants (Ka), sedimentation coefficients, and sensitivity to sulfhydryl-blocking reagents were found to be similar when hepatoma receptors were compared with the known properties of the liver receptor. Probably the most convincing criterion that the triamcinolone acetonide-binding macromolecules from the hepatomas are specific receptors is that 50 to 90% of the receptor can be depleted from hepatoma cytosol by treating rats with cortisol. In adrenalectomized tumor-bearing rats, the receptor levels in hepatomas 7787, 7800, 5123tc, and H-35 are comparable to or greater than receptor levels of host liver. However, tryptophan oxygenase was not responsive to glucocorticoids in hepatoma 7800 although receptor levels were quite high, and there were no indications that the receptor molecules were altered. Hepatomas 3683 and 3686F have low levels of receptor which may be related to resistance of these tumors to glucocorticoid treatment.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002729:Chloromercuribenzoates / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000378:metabolism / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D002729:Chloromercuribenzoates; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase; D014222:Triamcinolone Acetonide; D006854:Hydrocortisone