Skip to main content

Molecular Biological Aspects of the Human Androgen Receptor Relating to Disease

  • Chapter

Part of the book series: Hormones in Health and Disease ((HHD))

Abstract

The androgen receptor (AR) is required for normal male sexual development. It acts as a transcriptional regulatory protein subsequent to binding either of the two biologically active forms of androgen, testosterone or dihydrotestosterone. Although knowledge of the molecular mechanisms by which this ligand activated transcription factor induces target gene expression remains incomplete, recent advances in understanding the molecular events in androgen regulation have stemmed from the use of recombinant DNA techniques in studies of this complex protein.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akin JW, Behzadian A, Tho SPT and McDonough PG (1991): Evidence for a partial deletion in the androgen receptor gene in a phenotypic male with azoospermia. Am J Obstet Gynecol 165: 1891–1894.

    PubMed  CAS  Google Scholar 

  • Arbizu T, Santamaria J, Gomez JM, Quilez A and Serra JP (1983): A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure. J Neurol Sci 59: 371–382.

    Article  PubMed  CAS  Google Scholar 

  • Balthazart J, Foidart A, Wilson EM and Ball GF (1992): Immunocyto-chemical localization of androgen receptors in the male songbird and quail brain. J Comp Neurol 317: 407–420.

    Article  PubMed  CAS  Google Scholar 

  • Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS and Willard HF (1989): Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Amer J Hum Genet 44: 264–269.

    PubMed  CAS  Google Scholar 

  • Brown TR, Lubahn DB, Wilson EM, Joseph DR, French FS and Migeon CJ (1988): Deletion of the steroid binding domain of the human AR gene in one family with complete AIS; evidence of further genetic heterogeneity in this syndrome. Proc Natl Acad Sci USA 85: 8151–8155.

    Article  PubMed  CAS  Google Scholar 

  • Brown TR, Lubahn DB, Wilson EM, French FS, Migeon CJ and Corden JL (1990): Functional characterization of naturally occurring mutant androgen receptors from subjects with complete androgen insensitivity. Mol Endocrinol 4: 1759–1772.

    Article  PubMed  CAS  Google Scholar 

  • Chang C, Kokontis J and Liao S (1988): Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 240: 324–326.

    Article  PubMed  CAS  Google Scholar 

  • Crossley M, Ludwig M, Stowell KM, De Vos P, Olek K and Brownlee GG (1992): Recovery from Hemophilia B Leyden: an androgen responsive element in the factor IX promoter. Science 257: 377–379.

    Article  PubMed  CAS  Google Scholar 

  • DeBellis A, Quigley CA, Cariello NF, El-Awady MK, Sar M, Lane MV, Wilson EM and French FS (1992): Single base mutations in the human androgen receptor gene causing complete androgen insensitivity: rapid detection by a modified denaturing gradient gel electrophoresis technique. Mol Endocrinal, 6: 1909–1920.

    Article  CAS  Google Scholar 

  • Edwards A, Civitello A, Hammond HA and Caskey CT (1991): DNA typing and genetic mapping with trimeric and tetrameric tandem repeats. Am J Hum Genet 49: 746–756.

    PubMed  CAS  Google Scholar 

  • Fischbeck KH, Ionasescu V, Ritter AW, Ionasescu R, Davies K, Ball S, Bosch P, Burns T, Hausmanowa-Petrusewicz I, Borkowska J, Ringel SP and Stern LZ (1986): Localization of the gene for X-linked spinal muscular atrophy. Neurology, Cleveland 36: 1595–1598.

    Article  CAS  Google Scholar 

  • French FS, Lubahn DB, Brown TR, Simental JA, Quigley CA, Yarbrough WG, Tan JA, Sar M, Joseph DR, Evans BAJ, Hughes IA, Migeon CJ and Wilson EM (1990): Molecular basis of androgen insensitivity. Rec Prog Horm Res 46: 1–42.

    PubMed  CAS  Google Scholar 

  • Harris SE, Rong Z, Harris MA and Lubahn DB (1990): Androgen receptor in human prostate carcinoma LNCaP/Adep cells contains a mutation which alters the specificity of the steroid-dependent transcriptional activation region. Endocrine Society Abstracts, p. 93 (Atlanta, abstr).

    Google Scholar 

  • Harris SE, Harris MA, Rong Z, Hall J, Judge S, French FS, Joseph DR, Lubahn DB, Simental JA and Wilson EM (1991): In: Molecular and Cellular Biology of Prostate Cancer, Karr JP, Coffey DS, Smith RG, Tindall DJ, eds. New York: Plenum Press, 315–330.

    Chapter  Google Scholar 

  • Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D and O’Malley BW (1988): Point mutations in the human vitamin D receptor gene associated with hypocalcémic rickets. Science 242: 1702–1705.

    Article  PubMed  CAS  Google Scholar 

  • Hurley DM, Accili D, Stratakis CA, Karl M, Vamvakopoulos N, Rorer E, Constantine K, Taylor SI and Chrousos GP (1991): Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest 87: 680–686.

    Article  PubMed  CAS  Google Scholar 

  • Katchen B and Buxbaum S (1975): Disposition of a new nonsteroid antiandrogen, α,α,α-trifluoro-2-methyl-4′-nitro-m-propionotoluidide (flutamide) in men following a single oral 200 mg dose. J Clin Endocrinol Metab 41: 373–379.

    Article  PubMed  CAS  Google Scholar 

  • Klocker H, Kaspar F, Eberle J, Uberreiter S, Radmayr C and Bartsch G (1992): Point mutation in the DNA binding domain of the androgen receptor in two families with Reifenstein syndrome. Am J Hum Genet 50: 1318–1327.

    PubMed  CAS  Google Scholar 

  • La Spada AR, Wilson EM, Lubahn DB, Harding AE and Fischbeck KH (1991): AR gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77–79.

    Article  PubMed  Google Scholar 

  • Liao S, Howell DK and Chang TM (1974): Action of a nonsteroidal antiandrogen, flutamide, on the receptor binding and nuclear retention of 5 α-dihydrotestosterone in rat ventral prostate. Endocrinology 94: 1205–1209

    Article  PubMed  CAS  Google Scholar 

  • Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS and Wilson EM (1988): Cloning of human androgen receptor cDNA and localization to the X chromosome. Science 240: 327–330.

    Article  PubMed  CAS  Google Scholar 

  • Lubahn DB, Joseph DR, Sar M, Tan JA, Higgs HN, Larson RE, French FS and Wilson EM (1988b): The human androgen receptor: complementary DNA cloning, sequence analysis and gene expression in prostate. Mol Endocrinol 2: 1265–1275.

    Article  PubMed  CAS  Google Scholar 

  • Lund SD, Gallagher PM, Wang B, Porter SC and Ganschow RE (1991): Androgen responsiveness of the murine B-glucuronidase gene is associated with nuclease hypersensitivity, protein binding, and haplotype-specific sequence diversity within intron 9. Mol Cell Biol 11: 5426–5434.

    PubMed  CAS  Google Scholar 

  • Matsuura T, Demura T, Aimoto Y, Mizuno T, Moriwaka F and Tashiro K (1992): Androgen receptor abnormality in X-linked spinal and bulbar muscular atrophy. Neurology 42: 1724–1726.

    Article  PubMed  CAS  Google Scholar 

  • Mainwaring WIP, Mangan FR, Feherty PA and Freifeld M (1974): An investigation into the anti-androgenic properties of the nonsteroidal compound, SCH 13521 (4′-nitro-3′-trifluoromethylisobutyrylanilide). Mol Cell Endocrinol 1: 113–128.

    Article  PubMed  CAS  Google Scholar 

  • Marcelli M, Zoppi S, Grino PB, Griffin JE, Wilson JD and McPhaul MJ (1991): A mutation in the DNA binding domain of the androgen receptor gene causes complete testicular feminization in a patient with receptor positive androgen positive androgen resistance. J Clin Invest 87: 1123–1126.

    Article  PubMed  CAS  Google Scholar 

  • McPhaul MJ, Marcelli M, Tilley WD, Griffin JE and Wilson JD (1991): Androgen resistance caused by mutations in the androgen receptor gene. FASEB J 5: 2910–2915.

    PubMed  CAS  Google Scholar 

  • Neri R, Peets E and Watnick A (1979): Anti-androgenicity of flutamide and its metabolite Sch 16423. Biochem Soc Trans 7: 565–569.

    PubMed  CAS  Google Scholar 

  • Newmark JR, Hardy DO, Tonb DC, Carter BS, Epstein JI, Isaacs WB, Brown TR and Barrack ER (1992): Androgen receptor gene mutations in human prostate cancer. Proc Natl Acad Sci USA 89: 6319–6323.

    Article  PubMed  CAS  Google Scholar 

  • Pratt WB, Scherrer LC, Hutchison KA and Dalman FC (1992): A model of glucocorticoid receptor unfolding and stabilization by a heat shock protein complex. J Steroid Biochem Mol Biol 41: 223–229.

    Article  PubMed  CAS  Google Scholar 

  • Prior L, Bordet S, Trifiro MA, Mhatre A, Kaufman M, Pinsky L, Wrogeman K, Belsham DD, Pereira F, Greenberg C, Trapman J, Brinkman AO, Chang C and Liao S (1992): Replacement of arginine 773 by cysteine or histidine in the human androgen receptor causes complete androgen insensitivity with different receptor phenotypes. Am J Hum Genet 51: 143–155.

    PubMed  CAS  Google Scholar 

  • Quarmby VE, Kemppainen JA, Sar M, Lubahn DB, French FS and Wilson EM (1990): Expression of recombinant androgen receptor in cultured mammalian cells. Mol Endocrinol 4: 1399–1407.

    Article  PubMed  CAS  Google Scholar 

  • Quigley CA, Evans BAJ, Simental JA, Marschke KB, Sar M, Lubahn DB, Davies P, Hughes IA, Wilson EM and French FS (1992a): Complete AIS due to deletion of exon C of the AR gene highlights the functional importance of the second zinc finger of the AR in vivo. Mol Endocrinol 6: 1103–1112.

    Article  CAS  Google Scholar 

  • Quigley CA, Friedman KJ, Johnson A, Lafreniere RG, Silverman LM, Lubahn DB, Brown TR, Wilson EM, Willard HF and French FS (1992b): Complete deletion of the AR gene: definition of the null phenotype of the AIS and determination of carrier status. J Clin Endo Metab 74: 927–933.

    Article  CAS  Google Scholar 

  • Ris-Stalpers C, Trifiro MA, Kuiper GGJM, Jenster G, Romalo G, Sai T, van Rooij HCJ, Kaufman M, Rosenfield RL, Liao S, Schweikert HU, Trapman J, Pinsky L and Brinkmann AO (1991): Substitution of aspartic acid 686 by histidine or asparagine in the human androgen receptor leads to a functionally inactive protein with altered hormone binding characteristics. Mol Endocrinol 5: 1562–1569.

    Article  PubMed  CAS  Google Scholar 

  • Sar M and Stumpf WE (1977): Androgen concentration in motor neurons of cranial nerves and spinal cord. Science 197: 77–80.

    Article  PubMed  CAS  Google Scholar 

  • Sar M (1985): Application of the avidin-biotin complex technique for the localization of estradiol receptor in target tissues using monoclonal antibodies. In: Techniques in Immunocytochemistry, Bullock GR and Petrusz P, eds. New York: Academic Press, Vol 3, 43–54.

    Google Scholar 

  • Sar M, Lubahn DB, French FS and Wilson EM (1990): Immunohisto-chemical localization of the androgen receptor in rat and human tissues. Endocrinology 127: 3180–3186.

    Article  PubMed  CAS  Google Scholar 

  • Sar M, Hall S, Wilson EM and French FS (1993): Androgen regulation of Sertoli cells. In: The Sertoli Cell, Russell LD, and Griswold MD, eds. Clearwater FL, Cache River Press, pp 509–516.

    Google Scholar 

  • Simental JA, Sar M, Lane MV, French FS and Wilson EM (1991): Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 266: 510–518.

    PubMed  CAS  Google Scholar 

  • Sonnenschein C, Olea N, Pasanen ME and Soto AM (1989): Negative controls of cell proliferation: human prostate cancer cells and androgens. Cancer Res 49: 3474–3481.

    PubMed  CAS  Google Scholar 

  • Tan JA, Joseph DR, Quarmby VE, Lubahn DB, Sar M, French FS and Wilson EM (1988): The rat androgen receptor: primary structure, autoregulation of its messenger RNA and immunocytochemical localization of the receptor protein. Mol Endocrinol 2: 1276–1285.

    Article  PubMed  CAS  Google Scholar 

  • Varkarakis MJ, Kirdani RY, Yamanaka H, Murphy GP and Sandberg AA (1975): Prostatic effects of a nonsteroidal antiandrogen. Invest Urol 12: 275–284.

    PubMed  CAS  Google Scholar 

  • Veldscholte J, Ris-Stalpers C, Kuiper GGJM, Jenster G, Berrevoets C, Claassen E, van Rooij HCJ, Trapman J, Brinkman AO and Mulder E (1990): A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to antiandrogens. Biochem Biophys Res Commun 173: 534–540.

    Article  PubMed  CAS  Google Scholar 

  • Warner CL, Griffin JE, Wilson JD, Jacobs LD, Murray K, Fischbeck KH, Dickoff D and Griggs RC (1991): X-linked spinomuscular atrophy: a kindred with associated abnormal androgen receptor binding. Neurology 41(Suppl 1): 313.

    Article  Google Scholar 

  • Wilding G, Chen M and Gelmann EP (1989): Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens. The Prostate 14: 103–115.

    Article  PubMed  CAS  Google Scholar 

  • Wilson EM, Wright BT and Yarbrough WG (1986): The possible role of disulfide bond reduction in transformation of the 10S androgen receptor. J Biol Chem 261: 6501–6508.

    PubMed  CAS  Google Scholar 

  • Yarbrough WG, Quarmby VE, Simental JA, Joseph DR, Sar M, Lubahn DB, Olsen KL, French FS and Wilson EM (1990): A single base mutation in the androgen receptor gene causes androgen insensitivity in the Tfm rat. J Biol Chem 265: 8893–8900.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Birkhäuser Boston

About this chapter

Cite this chapter

Zhou, Zx., Sar, M., French, F.S., Wilson, E.M. (1994). Molecular Biological Aspects of the Human Androgen Receptor Relating to Disease. In: Moudgil, V.K. (eds) Steroid Hormone Receptors: Basic and Clinical Aspects. Hormones in Health and Disease. Birkhäuser Boston. https://doi.org/10.1007/978-1-4615-9849-7_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-9849-7_16

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4615-9851-0

  • Online ISBN: 978-1-4615-9849-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics