Abstract
Androgens and the androgen receptor (AR) are indispensable for expression of the male phenotype. The two most important androgens are testosterone and 5α-dihydrotestosterone. The elucidation of the mechanism of androgen action has a long history starting in the 19th century with the classical experiments by Brown-Séquard. In the 1960s the steroid hormone receptor concept was established and the AR was identified as a protein entity with a high affinity and specificity for testosterone and 5α-dihydrotestosterone. In addition, the enzyme 5α-reductase type 2 was discovered and found to catalyze the conversion of testosterone to the more active metabolite 5α-dihydrotestosterone. In the second half of the 1980s, the cDNA cloning of all steroid hormone receptors, including that of the AR, has been another milestone in the whole field of steroid hormone action. Despite two different ligands (testosterone and 5α-dihydrotestosterone), only one AR cDNA has been identified and cloned. The AR (NR3C4) is a ligand-dependent transcription factor and belongs to the family of nuclear hormone receptors which has 48 members in human. The current model for androgen action involves a multistep mechanism. Studies have provided insight into AR association with co-regulators involved in transcription initiation and on intramolecular interactions of the AR protein during activation. Knowledge about androgen action in the normal physiology and in disease states has increased tremendously after cloning of the AR cDNA. Several diseases, such as androgen insensitivity syndrome (AIS), prostate cancer and spinal bulbar muscular atrophy (SBMA), have been shown to be associated with alterations in AR function due to mutations in the AR gene or dysregulation of androgen signalling. A historical overview of androgen action and salient features of AR function in normal and disease states are provided herein.
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References
George, F.W., Wilson, J.D. 1994. Sex determination and differentiation. In: Knobil, E., Neill, J.D. (eds.) The Physiology of Reproduction, Chapter 1. pp. 3–28. Raven Press, New York, NY
Medvei, V.C. 1993. A History of Clinical Endocrinology. Parthenon Publishing Group, Carnforth, Lancashire, UK
Laqueur, E., de Jongh, S.E., Tausk, M. 1948. Hormonologie. Noord-Hollandsche Uitgevers Maatschappij, Amsterdam, The Netherlands
Jensen, E.V., Jacobson, H.I. 1960. Fate of steroidal estrogens in target tissues. In: Pincus, G., Volmer, E.P. (eds.) Biological Activities of Steroids in Relation to Cancer, pp. 161–174. Academic, New York, NY
Jensen, E.V., Jacobson, H.I., Walf, A.A., Frye, C.A. 2010. Estrogen action: a historic perspective on the implications of considering alternative approaches. Physiol Behav 99: 151–162
Toft, D., Gorski, J. 1966. A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci USA 55: 1574–1581
Mainwaring, W.I. 1969. A soluble androgen receptor in the cytoplasm of rat prostate. J Endocrinol 45: 531–541
Fang, S., Anderson, K.M., Liao, S. 1969. Receptor proteins for androgens. On the role of specific proteins in selective retention of 17-beta-hydroxy-5-alpha-androstan-3-one by rat ventral prostate in vivo and in vitro. J Biol Chem 244: 6584–6595
Baulieu, E.E., Jung, I. 1970. A prostatic cytosol receptor. Biochem Biophys Res Commun 38: 599–606
Jensen, E.V., Suzuki, T., Kawashima, T., Stumpf, W.E., Jungblut, P.W., DeSombre, E.R. 1968. A two-step mechanism for the interaction of estradiol with rat uterus. Proc Natl Acad Sci USA 59: 632–638
Bruchovsky, N., Wilson, J.D. 1968. The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one by rat prostate in vivo and in vitro. J Biol Chem 243: 2012–2021
Bruchovsky, N., Wilson, J.D. 1968. The intranuclear binding of testosterone and 5-alpha-androstan-17-beta-ol-3-one by rat prostate. J Biol Chem 243: 5953–5960
Baulieu, E.E., Lasnizki, I., Robel, P. 1968. Metabolism of testosterone and action of metabolites on prostate glands grown in organ culture. Nature 219: 1155–1156
Imperato-McGinley, J., Guerrero, L., Gautier, T., Peterson, R.E. 1974. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 186: 1213–1215
Chang, C.H., Rowley, D.R., Lobl, T.J., Tindall, D.J. 1982. Purification and characterization of androgen receptor from steer seminal vesicle. Biochemistry 21: 4102–4109
Wilson, E.M., Colvard, D.S. 1984. Factors that influence the interaction of androgen receptors with nuclei and nuclear matrix. Ann N Y Acad Sci 438: 85–100
Foekens, J.A., Peerbolte, R., Mulder, E., van der Molen, H.J. 1981. Characterization and partial purification of androgen receptors from ram seminal vesicles. Mol Cell Endocrinol 23: 173–186
van Loon, D., Voorhorst, M.M., Brinkmann, A.O., Mulder, E. 1988. Purification of the intact monomeric 110 kDa form of the androgen receptor from calf uterus to near homogeneity. Biochim Biophys Acta 970: 278–286
Wilson, E.M., French, F.S. 1979. Effects of proteases and protease inhibitors on the 4.5 S and 8 S androgen receptor. J Biol Chem 254: 6310–6319
Chang, C.H., Lobl, T.J., Rowley, D.R., Tindall, D.J. 1984. Affinity labeling of the androgen receptor in rat prostate cytosol with 17 beta-[(bromoacetyl)oxy]-5 alpha-androstan-3-one. Biochemistry 23: 2527–2533
Brinkmann, A.O., Kuiper, G.G., de Boer, W., Mulder, E., van der Molen, H.J. 1985. Photoaffinity labelling of androgen receptors with 17 beta-hydroxy-17 alpha-[3H]methyl-4,9,11-estratrien-3-one. Biochem Biophys Res Commun 126: 163–169
van Laar, J.H., Bolt-de Vries, J., Zegers, N.D., Trapman, J., Brinkmann, A.O. 1990. Androgen receptor heterogeneity and phosphorylation in human LNCaP cells. Biochem Biophys Res Commun 166: 193–200
Hollenberg, S.M., Weinberger, C., Ong, E.S., Cerelli, G., Oro, A., Lebo, R., Thompson, E.B., Rosenfeld, M.G., Evans, R.M. 1985. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318: 635–641
Green, S., Walter, P., Kumar, V., Krust, A., Bornert, J.M., Argos, P., Chambon, P. 1986. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320: 134–139
Greene, G.L., Gilna, P., Waterfield, M., Baker, A., Hort, Y., Shine, J. 1986. Sequence and expression of human estrogen receptor complementary DNA. Science 231: 1150–1154
Stocco, D.M., Clark, B.J. 1996. Regulation of the acute production of steroids in steroidogenic cells. Endocr Rev 17: 221–244
Miller, W.L. 1988. Molecular biology of steroid hormone synthesis. Endocr Rev 9: 295–318
Russell, D.W., Wilson, J.D. 1994. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem 63: 25–61
Andersson, S., Bishop, R.W., Russell, D.W. 1989. Expression cloning and regulation of steroid 5 alpha-reductase, an enzyme essential for male sexual differentiation. J Biol Chem 264: 16249–16255
Andersson, S., Berman, D.M., Jenkins, E.P., Russell, D.W. 1991. Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature 354: 159–161
Wilson, J.D., Griffin, J.E., Russell, D.W. 1993. Steroid 5 alpha-reductase 2 deficiency. Endocr Rev 14: 577–593
Randall, V.A. 1994. Role of 5 alpha-reductase in health and disease. Baillieres Clin Endocrinol Metab 8: 405–431
Grino, P.B., Griffin, J.E., Wilson, J.D. 1990. Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone. Endocrinology 126: 1165–1172
Committee, N.R.N. 1999. A unified nomenclature system for the nuclear receptor superfamily. Cell 97: 161–163
Evans, R.M. 1988. The steroid and thyroid hormone receptor superfamily. Science 240: 889–895
Laudet, V., Hanni, C., Coll, J., Catzeflis, F., Stehelin, D. 1992. Evolution of the nuclear receptor gene superfamily. EMBO J 11: 1003–1013
Robinson-Rechavi, M., Carpentier, A.S., Duffraisse, M., Laudet, V. 2001. How many nuclear hormone receptors are there in the human genome? Trends Genet 17: 554–556
Migliaccio, A., Castoria, G., Di Domenico, M., de Falco, A., Bilancio, A., Lombardi, M., Barone, M.V., Ametrano, D., Zannini, M.S., Abbondanza, C., Auricchio, F. 2000. Steroid-induced androgen receptor–oestradiol receptor beta-Src complex triggers prostate cancer cell proliferation. EMBO J 19: 5406–5417
Kousteni, S., Bellido. T., Plotkin, L.I., O’Brien, C.A., Bodenner, D.L., Han, L., Han, K., DiGregorio, G.B., Katzenellenbogen, J.A., Katzenellenbogen, B.S., Roberson, P.K., Weinstein, R.S., Jilka, R.L., Manolagas, S.C. 2001. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104: 719–730
Chang, C.S., Kokontis, J., Liao, S.T. 1988. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 240: 324–326
Lubahn, D.B., Joseph, D.R., Sullivan, P.M., Willard, H.F., French, F.S., Wilson, E.M. 1988. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240: 327–330
Trapman, J., Klaassen, P., Kuiper, G.G., van der Korput, J.A., Faber, P.W., van Rooij, H.C., Geurts van Kessel, A., Voorhorst, M.M., Mulder, E., Brinkmann, A.O. 1988. Cloning, structure and expression of a cDNA encoding the human androgen receptor. Biochem Biophys Res Commun 153: 241–248
Tilley, W.D., Marcelli, M., Wilson, J.D., McPhaul, M.J. 1989. Characterization and expression of a cDNA encoding the human androgen receptor. Proc Natl Acad Sci USA 86: 327–331
Brown, C.J., Goss, S.J., Lubahn, D.B., Joseph, D.R., Wilson, E.M., French, F.S., Willard, H.F. 1989. Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet 44: 264–269
Kuiper, G.G., Faber. P.W., van Rooij, H.C., van der Korput, J.A., Ris-Stalpers, C., Klaassen, P., Trapman, J., Brinkmann, A.O. 1989. Structural organization of the human androgen receptor gene. J Mol Endocrinol 2: R1–R4
Lubahn, D.B., Brown, T.R., Simental, J.A., Higgs, H.N., Migeon, C.J., Wilson, E.M., French, F.S. 1989. Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci USA 86: 9534–9538
Faber, P.W., van Rooij, H.C., van der Korput, H.A., Baarends, W.M., Brinkmann, A.O., Grootegoed, J.A., Trapman, J. 1991. Characterization of the human androgen receptor transcription unit. J Biol Chem 266: 10743–10749
Tilley, W.D., Marcelli, M., McPhaul, M.J. 1990. Expression of the human androgen receptor gene utilizes a common promoter in diverse human tissues and cell lines. J Biol Chem 265: 13776–13781
Faber, P.W., Kuiper, G.G., van Rooij, H.C., van der Korput, J.A., Brinkmann, A.O., Trapman, J. 1989. The N-terminal domain of the human androgen receptor is encoded by one, large exon. Mol Cell Endocrinol 61: 257–262
Sleddens, H.F., Oostra, B.A., Brinkmann, A.O., Trapman, J. 1993. Trinucleotide (GGN) repeat polymorphism in the human androgen receptor (AR) gene. Hum Mol Genet 2: 493
Gottlieb, B., Beitel, L.K., Wu, J.H., Trifiro, M. 2004. The androgen receptor gene mutations database (ARDB): 2004 update. Hum Mutat 23: 527–533
van Laar, J.H., Bolt-de Vries, J., Voorhorst-Ogink, M.M., Brinkmann, A.O. 1989. The human androgen receptor is a 110 kDa protein. Mol Cell Endocrinol 63: 39–44
Jenster, G., de Ruiter, P.E., van der Korput, H.A., Kuiper, G.G., Trapman, J., Brinkmann, A.O. 1994. Changes in the abundance of androgen receptor isotypes: effects of ligand treatment, glutamine-stretch variation, and mutation of putative phosphorylation sites. Biochemistry 33: 14064–14072
Kuiper, G.G., Brinkmann, A.O. 1995. Phosphotryptic peptide analysis of the human androgen receptor: detection of a hormone-induced phosphopeptide. Biochemistry 34: 1851–1857
Kuiper, G.G., de Ruiter, P.E., Grootegoed, J.A., Brinkmann, A.O. 1991. Synthesis and post-translational modification of the androgen receptor in LNCaP cells. Mol Cell Endocrinol 80: 65–73
Wong, H.Y., Burghoorn, J.A., Van Leeuwen, M., De Ruiter, P.E., Schippers, E., Blok, L.J., Li, K.W., Dekker, H.L., De Jong, L., Trapman, J., Grootegoed, J.A., Brinkmann, A.O. 2004. Phosphorylation of androgen receptor isoforms. Biochem J 383: 267–276
Misrahi, M., Atger, M., d’Auriol, L., Loosfelt, H., Meriel, C., Fridlansky, F., Guiochon-Mantel, A., Galibert, F., Milgrom, E. 1987. Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys Res Commun 143: 740–748
Arriza, J.L., Weinberger, C., Cerelli, G., Glaser, T.M., Handelin, B.L., Housman, D.E., Evans, R.M. 1987. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237: 268–275
Kuiper, G.G., Enmark, E., Pelto-Huikko, M., Nilsson, S., Gustafsson, J.A. 1996. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93: 5925–5930
Sleddens, H.F., Oostra, B.A., Brinkmann, A.O., Trapman, J. 1992. Trinucleotide repeat polymorphism in the androgen receptor gene (AR). Nucleic Acids Res 20: 1427
Boehmer, A.L., Brinkmann, A.O., Niermeijer, M.F., Bakker, L., Halley, D.J., Drop, S.L. 1997. Germ-line and somatic mosaicism in the androgen insensitivity syndrome: implications for genetic counseling. Am J Hum Genet 60: 1003–1006
Li, S.L., Ting, S.S., Lindeman, R., French, R., Ziegler, J.B. 1998. Carrier identification in X-linked immunodeficiency diseases. J Paediatr Child Health 34: 273–279
Nance, M.A. 1997. Clinical aspects of CAG repeat diseases. Brain Pathol 7: 881–900
Kazemi-Esfarjani, P., Trifiro, M.A., Pinsky, L. 1995. Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG) n -expanded neuronopathies. Hum Mol Genet 4: 523–527
Jenster, G., van der Korput, H.A., Trapman, J., Brinkmann, A.O. 1995. Identification of two transcription activation units in the N-terminal domain of the human androgen receptor. J Biol Chem 270: 7341–7346
Claessens, F., Denayer, S., Van Tilborgh, N., Kerkhofs, S., Helsen, C., Haelens, A. 2008. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl Recept Signal 6: e008
Lavery, D.N., McEwan, I.J. 2008. Structural characterization of the native NH2-terminal transactivation domain of the human androgen receptor: a collapsed disordered conformation underlies structural plasticity and protein-induced folding. Biochemistry 47: 3360–3369
Langley, E., Zhou, Z.X., Wilson, E.M. 1995. Evidence for an anti-parallel orientation of the ligand-activated human androgen receptor dimer. J Biol Chem 270: 29983–29990
Doesburg, P., Kuil, C.W., Berrevoets, C.A., Steketee, K., Faber, P.W., Mulder, E., Brinkmann, A.O., Trapman, J. 1997. Functional in vivo interaction between the amino-terminal, transactivation domain and the ligand binding domain of the androgen receptor. Biochemistry 36: 1052–1064
Berrevoets, C.A., Doesburg, P., Steketee, K., Trapman, J., Brinkmann, A.O. 1998. Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2). Mol Endocrinol 12: 1172–1183
Zhou, Z.X., Lane, M.V., Kemppainen, J.A., French, F.S., Wilson, E.M. 1995. Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability. Mol Endocrinol 9: 208–218
Centenera, M.M., Harris, J.M., Tilley, W.D., Butler, L.M. 2008. The contribution of different androgen receptor domains to receptor dimerization and signaling. Mol Endocrinol 22: 2373–2382
Luisi, B.F., Xu, W.X., Otwinowski, Z., Freedman, L.P., Yamamoto, K.R., Sigler, P.B. 1991. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352: 497–505
Shaffer, P.L., Jivan, A., Dollins, D.E., Claessens, F., Gewirth, D.T. 2004. Structural basis of androgen receptor binding to selective androgen response elements. Proc Natl Acad Sci USA 101: 4758–4763
Jakob, M., Kolodziejczyk, R., Orlowski, M., Krzywda, S., Kowalska, A., Dutko-Gwozdz, J., Gwozdz, T., Kochman, M., Jaskolski, M., Ozyhar, A. 2007. Novel DNA-binding element within the C-terminal extension of the nuclear receptor DNA-binding domain. Nucleic Acids Res 35: 2705–2718
Fu, M., Wang, C., Zhang, X., Pestell, R.G. 2004. Acetylation of nuclear receptors in cellular growth and apoptosis. Biochem Pharmacol 68: 1199–1208
Brinkmann, A.O., Trapman, J. 2000. Genetic analysis of androgen receptors in development and disease. Adv Pharmacol 47: 317–341
Matias, P.M., Donner, P., Coelho, R., Thomaz, M., Peixoto, C., Macedo, S., Otto, N., Joschko, S., Scholz, P., Wegg, A., Basler, S., Schafer, M., Ruff, M., Egner, U., Carrondo, M.A. 2000. Structural evidence for ligand specificity in the binding domain of the human androgen receptor: implications for pathogenic gene mutations. J Biol Chem 275: 26164–26171
Sack, J.S., Kish, K.F., Wang, C., Attar, R.M., Kiefer, S.E., An, Y., Wu, G.Y., Scheffler, J.E., Salvati, M.E., Krystek, S.R., Weinmann, R., Einspahr, H.M. 2001. Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci USA 98: 4904–4909
Pereira de Jesus-Tran, K., Cote, P.L., Cantin, L., Blanchet, J., Labrie, F., Breton, R. 2006. Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity. Protein Sci 15: 987–999
Estebanez-Perpina, E., Arnold, L.A., Nguyen, P., Rodrigues, E.D., Mar, E., Bateman, R., Pallai, P., Shokat, K.M., Baxter, J.D., Guy, R.K., Webb, P., Fletterick, R.J. 2007. A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci USA 104: 16074–16079
Jenster, G., van der Korput, H.A., van Vroonhoven, C., van der Kwast, T.H., Trapman, J., Brinkmann, A.O. 1991. Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Mol Endocrinol 5: 1396–1404
Hollenberg, S.M., Evans, R.M. 1988. Multiple and cooperative trans-activation domains of the human glucocorticoid receptor. Cell 55: 899–906
Kuil, C.W., Mulder, E. 1994. Mechanism of antiandrogen action: conformational changes of the receptor. Mol Cell Endocrinol 102: R1–R5
Kuil, C.W., Berrevoets, C.A., Mulder, E. 1995. Ligand-induced conformational alterations of the androgen receptor analyzed by limited trypsinization. Studies on the mechanism of antiandrogen action. J Biol Chem 270: 27569–27576
Berrevoets, C.A., Umar, A., Trapman, J., Brinkmann, A.O. 2004. Differential modulation of androgen receptor transcriptional activity by the nuclear receptor co-repressor (N-CoR). Biochem J 379: 731–738
Reifenstein, E.C., Jr. 1947. Hereditary familial hypogonadism. Proc Am Fed Clin Res 3: 86
Wilson, J.D., Harrod, M.J., Goldstein, J.L., Hemsell, D.L., MacDonald, P.C. 1974. Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. N Engl J Med 290: 1097–1103
Geissler, W.M., Davis, D.L., Wu, L., Bradshaw, K.D., Patel, S., Mendonca, B.B., Elliston, K.O., Wilson, J.D., Russell, D.W., Andersson, S. 1994. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet 7: 34–39
Hughes, I.A. 2008. Disorders of sex development: a new definition and classification. Best Pract Res Clin Endocrinol Metab 22: 119–134
Lu, J., Danielsen, M. 1996. A Stu I polymorphism in the human androgen receptor gene (AR). Clin Genet 49: 323–324.
Ris-Stalpers, C., Verleun-Mooijman, M.C., de Blaeij, T.J., Degenhart, H.J., Trapman, J., Brinkmann, A.O. 1994. Differential splicing of human androgen receptor pre-mRNA in X-linked Reifenstein syndrome, because of a deletion involving a putative branch site. Am J Hum Genet 54: 609–617
Davies, H.R., Hughes, I.A., Patterson, M.N. 1995. Genetic counselling in complete androgen insensitivity syndrome: trinucleotide repeat polymorphisms, single-strand conformation polymorphism and direct detection of two novel mutations in the androgen receptor gene. Clin Endocrinol (Oxf) 43: 69–77
Kohler, B., Lumbroso, S., Leger, J., Audran, F., Grau, E.S., Kurtz, F., Pinto, G., Salerno, M., Semitcheva, T., Czernichow, P., Sultan, C. 2005. Androgen insensitivity syndrome: somatic mosaicism of the androgen receptor in seven families and consequences for sex assignment and genetic counseling. J Clin Endocrinol Metab 90: 106–111
Dowsing, A.T., Yong, E.L., Clark, M., McLachlan, R.I., de Kretser, D.M., Trounson, A.O. 1999. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene [In Process Citation]. Lancet 354: 640–643
Mifsud, A., Sim, C.K., Boettger-Tong, H., Moreira, S., Lamb, D.J., Lipshultz, L.I., Yong, E.L. 2001. Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility. Fertil Steril 75: 275–281
Wallerand, H., Remy-Martin, A., Chabannes, E., Bermont, L., Adessi, G., Bittard, H. 2001. Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility. Fertil Steril 76: 769–774
Kennedy, W.R., Alter, M., Sung, J.H. 1968. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology 18: 671–680
Arbizu, T., Santamaria, J., Gomez, J.M., Quilez, A., Serra, J.P. 1983. A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure. J Neurol Sci 59: 371–382
Greenland, K.J., Zajac, J.D. 2004. Kennedy’s disease: pathogenesis and clinical approaches. Intern Med J 34: 279–286
La Spada, A.R, Wilson, E.M., Lubahn, D.B., Harding, A.E., Fischbeck, K.H. 1991. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77–79
Caskey, C.T., Pizzuti, A., Fu, Y.H., Fenwick, R.G., Jr., Nelson, D.L. 1992. Triplet repeat mutations in human disease. Science 256: 784–789
Edwards, A., Hammond, H.A., Jin, L., Caskey, C.T., Chakraborty, R. 1992. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics 12: 241–253
Robitaille, Y., Lopes-Cendes, I., Becher, M., Rouleau, G., Clark, A.W. 1997. The neuropathology of CAG repeat diseases: review and update of genetic and molecular features. Brain Pathol 7: 901–926
Gronberg, H. 2003. Prostate cancer epidemiology. Lancet 361: 859–864
van der Kwast, T.H., Schalken, J., Ruizeveld de Winter, J.A., van Vroonhoven, C.C., Mulder, E., Boersma, W., Trapman, J. 1991. Androgen receptors in endocrine-therapy-resistant human prostate cancer. Int J Cancer 48: 189–193
Feldman, B.J., Feldman, D. 2001. The development of androgen-independent prostate cancer. Nat Rev Cancer 1: 34–45
Grossmann, M.E., Huang, H., Tindall, D.J. 2001. Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst 93: 1687–1697
Edwards, J., Krishna, N.S., Witton, C.J., Bartlett, J.M. 2003. Gene amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res 9: 5271–5281
Edwards, J., Krishna, N.S., Grigor, K.M., Bartlett, J.M. 2003. Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br J Cancer 89: 552–556
Visakorpi, T., Hyytinen, E., Koivisto, P., Tanner, M., Keinanen, R., Palmberg, C., Palotie, A., Tammela, T., Isola, J., Kallioniemi, O.P. 1995. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 9: 401–406
Veldscholte, J., Ris-Stalpers, C., Kuiper, G.G., Jenster, G., Berrevoets, C., Claassen, E., van Rooij, H.C., Trapman, J., Brinkmann, A.O., 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 anti-androgens. Biochem Biophys Res Commun 173: 534–540
Zhao, X.Y., Malloy, P.J., Krishnan, A.V., Swami, S., Navone, N.M., Peehl, D.M., Feldman, D. 2000. Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat Med 6: 703–706
La Spada, AR. 2006. Spinal and bulbar muscular atrophy. In: Pagon, R.A., Bird, T.C., Dolan, C.R., Stephens, K. (eds.) GeneReviews [Internet]. University of Washington, Seattle, WA. (1993–1999 Feb 26 [updated 2006 Dec 28])
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Brinkmann, A.O. (2011). Molecular Mechanisms of Androgen Action – A Historical Perspective. In: Saatcioglu, F. (eds) Androgen Action. Methods in Molecular Biology, vol 776. Humana Press. https://doi.org/10.1007/978-1-61779-243-4_1
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