原发性肝细胞癌中雄激素高亲和力结合位点的表征

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

作者信息

Wilkinson M L, Iqbal M J, Williams R

出版信息

Clin Chim Acta. 1985 Oct 31;152(1-2):105-13. doi: 10.1016/0009-8981(85)90181-0.

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 5 alpha-dihydrotestosterone (DHT) was detected in cytosol (11.5-21 fmol/mg, Kd 1.5 X 10(-10)-3.1 X 10(-11) mol/l) and in nucleosol (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, 5 alpha-androstan-3 beta, 17 beta-diol, androst-5-ene-3 beta,17 beta-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.

摘要

据报道，在肝细胞癌（HCC）和胎儿肝脏中存在雄激素受体（AR），而在正常成人肝脏中不存在，随后采用一种新的微量测定法对AR进行了进一步研究。所检查的组织包括：3例HCC患者的5份伴有周围正常肝脏的样本；5份肝硬化肝脏样本以及1例儿童HCC标本。在5份HCC样本的胞质溶胶（11.5 - 21飞摩尔/毫克，解离常数1.5×10⁻¹⁰ - 3.1×10⁻¹¹摩尔/升）和核溶胶（8.7 - 11.4飞摩尔/毫克，6.7 - 1.4×10⁻¹¹摩尔/升）中检测到5α - 双氢睾酮（DHT）的高亲和力结合。所有其他肝脏样本仅表现出非特异性结合。竞争研究表明，DHT、睾酮、雄烯二酮、5α - 雄烷 - 3β,17β - 二醇、雄甾 - 5 - 烯 - 3β,17β - 二醇和醋酸环丙孕酮作用于同一受体结合位点，3H - DHT的相对取代率分别为100%、85.7%、77.4%、67.8%、34.5%和60.2%。在前列腺组织和HCC组织中均证实存在3.5S胞质溶胶受体以及2.8S和4S核溶胶受体模式。这些研究证实了HCC中存在胞质溶胶和核溶胶雄激素受体，其具有与人类前列腺AR相似的特征。