Characterisation of high affinity binding sites of androgens in primary hepatocellular carcinoma

Abstract

The reported presence of androgen receptors (AR) in hepatocellular carcinoma (HCC) and foetal liver, but not in normal adult human liver, has been followed by further study of AR employing a new microassay. Tissues examined were: 5 samples of HCC with surrounding normal liver in 3 cases; 5 samples of cirrhotic liver and a single specimen of HCC in a child. High affinity binding of 5α-dihydrotestosterone (DHT) was detected in cytosol (11.5–21 fmol/mg, K d 1.5 × 10 −10−3.1 × 10 −11 mol/l) and in nucelosol (8.7–11.4 fmol/mg, 6.7−1.4 x 10 −11 mol/l) of the 5 HCC samples. All other liver samples exhibited non-specific binding only. Competition studies indicated that DHT, testosterone, androstenedione, 5α-androstan-3β, 17ß-diol, androst-5-ene-3β, 17β-diol and cyproterone acetate were acting at the same receptor binding site, relative displacement of 3H-DHT being 100, 85.7, 77.4, 67.8, 34.5 and 60.2 per cent respectively. Presence of 3.5S cytosolic and both 2.8S and 4S nucleosolic receptor patterns were demonstrated in both prostatic and HCC tissue. These studies confirm the presence of a cytosolic and nucleosolic androgen receptor in HCC which possesses similar characteristics to the AR of human prostate.