SUBCELLULAR-DISTRIBUTION OF ANDROGEN RECEPTORS IN HUMAN NORMAL, BENIGN HYPERPLASTIC, AND MALIGNANT PROSTATIC TISSUES - CHARACTERIZATION OF NUCLEAR SALT-RESISTANT RECEPTORS

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (3) , 1107-1116
Abstract
Two populations of nuclear androgen receptors were characterized in human prostatic tissue. The levels and proportions of each differed in normal prostates, benign hyperplastic prostates (BPH) and malignant prostates. A significant percentage (35-50%) of total nuclear androgen receptors was associated with the salt-resistant nuclear matrix fraction. The remainder were easily extracted from nuclei by 0.6 M KCl. Optimal conditions for measuring receptors in both compartments involved the use of an inhibitor of proteolysis (phenylmethylsulfonyl fluoride) and the omission of dithiothreitol from buffers. In the presence of dithiothreitol, most of the nuclear salt-resistant receptors were rendered salt extractable. Cytosol androgen receptor levels were not significantly different in normal, BPH or malignant prostatic tissues. The levels and distribution of nuclear salt-extractable and salt-resistant androgen receptors exhibited characteristic patterns. Compared to normal prostatic tissue, nuclear salt-extractable receptors were significantly elevated in both BPH and cancer, whereas nuclear salt-resistant receptors were elevated in BPH but not in cancer. The ratio of salt-extractable to salt-resistant receptors was .apprx. 1:1 in both normal and BPH tissues and 2:1 in cancer. A microassay was developed for the measurement of androgen receptors in the 3 subcellular compartments of needle biopsy specimens of prostatic cancer.