Steroid receptors in the human prostate. Detection of tissue-specific androgen binding in prostate cancer.
We have searched for tissue-specific binding of 5alpha-androstan-17beta-ol-3-one (5alpha-dihydrotestosterone; 5alpha-DHT) in cytosols prepared from 25 surgically obtained benign prostatic hypertrophy (BPH) samples and in 3 tissue specimens containing prostate cancer cells. The distinction between steroid-receptor complexes and ligand binding to serum sex hormone-binding globulin (SHBG) was facilitated by combination experiments involving both sucrose gradient ultracentrifugation and agar gel electrophoresis. Gradient analysis of a cytosol prepared from a cervical lymph node (CLN) containing metastatic prostate tissue, revealed both 8-S and 4-S forms of high affinity (charcoal stable) 5alpha-[3H]DHT binding. When electrophoresis was performed on gradient fractions from these zones, anodally migrating steroid-receptor complexes were found only in the 8-S peak, the 4-S region containing radioligand bound to cathodally directed SHBG. In similar experiments with two BPH samples heavily invaded with prostate cancer cells only a single 4-S peak of radioligand binding was detected. Its multicomponent nature was uncovered electrophoretically when, in addition to SHBG, saturable, androgen binding molecules appeared anodally. Their incomplete resolution from SHBG on a gradient might have prevented their identification had this been the only method used. In contrast to the cancer-containing tissues, no saturable 5alpha-[3H]-DHT binding, other than that to SHBG, was detected in any of the BPH samples analysed. It is considered that, of the methods currently available, agar gel electrophoresis may be particularly useful for further investigations into the possible multicomponent nature of androgen binding of tissue origin in the human prostate.
D000230:Adenocarcinoma / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000302:isolation & purification / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone