Androgen Receptors in Prostatic Cancer

  • R Ghanadian
  • G Auf
  • G D Chisholm
Part of the Ettore Majorana International Science Series book series (EMISS, volume 1)

Abstract

There are good grounds for the premise that measurement of androgen receptor proteins in carcinoma of the prostate may be of value in the prediction of responsiveness to hormone manipulation. Although a receptor protein which binds dihydrotestosterone has been identified and characterised in the human prostate by sucrose density gradient centrifugation and column chromatography, routine quantitative measurements in human prostatic tissues have been beset by a number of problems in methodology. In the first place, the high level of sex hormone binding protein (SHBG) and of endogenous androgens in prostatic tissues interfere with the receptor assay and the earlier dextran charcoal technique (Mobbe et al, 1975) has proved to be unreliable. In the dextran charcoal method cytosol is labelled with either 3H testosterone or dihydrotestosterone. The free and loosely bound steroids are then separated from tightly bound steroids by the addition of dextran coated charcoal. However, due to the high affinity of androgens to SHBG it proved impossible to separate SHBG from androgen receptors using this technique. This method was replaced by the “Agar gel electrophoresis technique” (Wagner, 1972), which can separate SHBG from androgen receptors by agar gel electrophoresis, but in turn has the disadvantage that only (free) receptors are measured.

Keywords

Cortisol Testosterone Fractionation Progesterone Androgen 

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References

  1. 1.
    Auf, G. and Ghanadian, R., A comparative study of the binding of androgen receptors to dihydrotestosterone, progesterone and methyltrienolone. Proceeding of the Pharmacological modulation of steroid action, Turin, July 1978. In Press.Google Scholar
  2. 2.
    Bonne, C. and Raynaud, J. P., Methyltrienolone, a specific ligand for cellular androgen receptors. Steroids, 26, 227–230 (1975).PubMedCrossRefGoogle Scholar
  3. 3.
    Cowan, R. A., Cowan, S. A., Giles, C. A. and Grant, J. K., Prostatic distribution of sex hormone-binding globulin and cortisol-binding globulin in benign hyperplasia. Journal of Endocrinology, 71, 121–136 (1976).PubMedCrossRefGoogle Scholar
  4. 4.
    Cowan, R. A., Cowan, S. A., Grant, J. K. and Elder, H. T., Biochemical investigations of separate epithelium and stroma from benign hyperplastic prostate tissue. Journal of Endocrinology, 74, 111–120 (1977).PubMedCrossRefGoogle Scholar
  5. 5.
    Cowan, R. A., Cowan, S. A. and Grant, J. K., Binding of methyltrienolone (R1881) to a progesterone receptor-like component of human prostatic cytosol. Journal of Endocrinology 74, 281–289 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    Ghanadian, R., Auf, G., Chaloner, P. J. and Chisholm, G. D., The use of methyltrienolone in the measurement of the free and bound cytoplasmic receptor for dihydrotestosterone in benign hypertrophied human prostate. Journal of Steroid Biochemistry, 9, 325–330 (1978a).PubMedCrossRefGoogle Scholar
  7. 7.
    Ghanadian, R., Auf, G., Chisholm, G. D. and O’Donoghue, E. P. N Receptor proteins for androgens in prostatic disease. Brit. J. Urol. (1978) (In Press).Google Scholar
  8. 8.
    Mobbs, B. G., Johson, I. E. and Connolly, J. G., In vitro assay of androgen binding by human prostate. Journal of Steroid Biochemistry, 6, 453–458 (1975).Google Scholar
  9. 9.
    Rosen, V., Jung, I., Baulieu, E. E. and Robels, P., Androgen- binding proteins in human benign prostatic hypertrophy. Journal of Clinical Endocrinology and Metabolism, 41, 761–770 (1975).PubMedCrossRefGoogle Scholar
  10. 10.
    Wagner, R. K., Characterisation and assay of steroid hormone receptors and steroid binding serum proteins by agargel electro phoresis at low temperatures. Hopper Seyler’s Z. Physiol. Chem 353, 1235–1245 (1972).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • R Ghanadian
    • 1
    • 2
  • G Auf
    • 1
    • 2
  • G D Chisholm
    • 1
    • 2
  1. 1.Prostate Research LaboratoryRoyal Postgraduate Medical SchoolEngland
  2. 2.Institute of UrologyUniversity of LondonLondonEngland

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