Decreased androgen receptor-ligand affinity in hepatocellular carcinomas

ABSTRACT

Human liver tissues from normal, cirrhotic and hepatocellular carcinomas [HCC] were analyzed by Scatchard plots for cytosolic androgen binding capacities using methyltrienolone. The ranges and the means of the cytosolic androgen binding capacities for the normal tissue [and the normal surroundings], the cirrhotic tissue, and the HCC's in fmoles per mg protein were 3.7-47.9 [mean +/- SEM = 23.7 +/- 7.9], 3.0 - 17.3 [mean +/- SEM = 7.9 +/- 4.7] and 2.8 -14.6 [mean + SEM= 6.8 +/- 2.7], respectively. The ranges and the means of the dissociation constants [Kd] in M X 10[10] for the normal, cirrhotic and the HCC tissues were 5.7-16.0 [mean +/- SEM = 8.8 +/- 1.8], 6.7- 68.5 [mean +/- SEM = 30.1 +/- 19.3] and 35.6 - 60.0 [mean + SEM = 47.8 +/- 5.4], respectively. A significant decrease in cytosolic androgen binding capacity and a highly significant increase [P<0.001] in Kd value [or a decrease in the affinity] of the HCC androgen receptors, as compared to normal tissues, could possibly be explained by a decrease in the level of phosphorylation of the receptor as a result of a defect in the metabolic regulation of the cancerous tissues