Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy

Hormones and Behavior

Volumn 53, Issue 5, 2008, Pages 729-740

  Monks, Douglas Ashley ^a,b   Rao, Pengcheng ^a   Mo, Kaiguo ^a   Johansen, Jamie Ann ^c   Lewis, Gareth ^a   Kemp, Michael Quentin ^c  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Axonopathy; Myopathy; Neuromuscular systems; Polyglutamine disease; Sexual dimorphism; Testosterone

Indexed keywords

ANDROGEN RECEPTOR; POLYGLUTAMINE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; DEGENERATIVE DISEASE; FEMALE; GENE OVEREXPRESSION; HUMAN; KENNEDY DISEASE; MALE; MOTONEURON; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SKELETAL MUSCLE; TRANSGENIC MOUSE; WILD TYPE;

ANIMALS; HUMANS; MUSCLE, SKELETAL; MUSCULAR ATROPHY, SPINAL; NEURONS; RECEPTORS, ANDROGEN;

EID: 42649138878     PISSN: 0018506X     EISSN: 10956867     Source Type: Journal    
DOI: 10.1016/j.yhbeh.2007.12.009     Document Type: Article

References (76)

1. Abel A., Walcott J., Woods J., Duda J., and Merry D.E. Expression of expanded repeat androgen receptor produces neurologic disease in transgenic mice. Hum. Mol. Genet. 10 2 (2001) 107-116
2. Adachi H., Kume A., Li M., Nakagomi Y., Niwa H., Do J., Sang C., Kobayashi Y., Doyu M., and Sobue G. Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death. Hum. Mol. Genet. 10 10 (2001) 1039-1048
3. Adachi H., Katsuno M., Minamiyama M., Waza M., Sang C., Nakagomi Y., Kobayashi Y., Tanaka F., Doyu M., Inukai A., Yoshida M., Hashizume Y., and Sobue G. Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain 128 Pt 3 (2005) 659-670
4. Atsuta N., Watanabe H., Ito M., Banno H., Suzuki K., Katsuno M., Tanaka F., Tamakoshi A., and Sobue G. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain 129 Pt 6 (2006) 1446-1455
5. Avila D.M., Allman D.R., Gallo J.M., and McPhaul M.J. Androgen receptors containing expanded polyglutamine tracts exhibit progressive toxicity when stably expressed in the neuroblastoma cell line, SH-SY 5Y. Exp. Biol. Med. (Maywood) 228 8 (2003) 982-990
6. Bailey C.K., Andriola I.F., Kampinga H.H., and Merry D.E. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 11 5 (2002) 515-523
7. Banno H., Adachi H., Katsuno M., Suzuki K., Atsuta N., Watanabe H., Tanaka F., Doyu M., and Sobue G. Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: a pathogenic marker. Ann. Neurol. 59 3 (2006) 520-526
8. Becker M., Martin E., Schneikert J., Krug H.F., and Cato A.C. Cytoplasmic localization and the choice of ligand determine aggregate formation by androgen receptor with amplified polyglutamine stretch. J. Cell Biol. 149 2 (2000) 255-262
9. Bingham P.M., Scott M.O., Wang S., McPhaul M.J., Wilson E.M., Garbern J.Y., Merry D.E., and Fischbeck K.H. Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nat. Genet. 9 2 (1995) 191-196
10. Bowman A.B., Yoo S.Y., Dantuma N.P., and Zoghbi H.Y. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum. Mol. Genet. 14 5 (2005) 679-691
11. Bowman A.B., Lam Y.C., Jafar-Nejad P., Chen H.K., Richman R., Samaco R.C., Fryer J.D., Kahle J.J., Orr H.T., and Zoghbi H.Y. Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat. Genet. 39 3 (2007) 373-379
12. Breedlove S.M., and Arnold A.P. Sexually dimorphic motor nucleus in the rat lumbar spinal cord: response to adult hormone manipulation, absence in androgen-insensitive rats. Brain Res. 225 2 (1981) 297-307
13. Brennan K.J., and Hardeman E.C. Quantitative analysis of the human alpha-skeletal actin gene in transgenic mice. J. Biol. Chem. 268 1 (1993) 719-725
14. Brooks B.P., Paulson H.L., Merry D.E., Salazar-Grueso E.F., Brinkmann A.O., Wilson E.M., and Fischbeck K.H. Characterization of an expanded glutamine repeat androgen receptor in a neuronal cell culture system. Neurobiol. Dis. 3 4 (1997) 313-323
15. Casella R., Maduro M.R., Misfud A., Lipshultz L.I., Yong E.L., and Lamb D.J. Androgen receptor gene polyglutamine length is associated with testicular histology in infertile patients. J. Urol. 169 1 (2003) 224-227
16. Chevalier-Larsen E.S., O'Brien C.J., Wang H., Jenkins S.C., Holder L., Lieberman A.P., and Merry D.E. Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy. J. Neurosci. 24 20 (2004) 4778-4786
17. Darrington R.S., Butler R., Leigh P.N., McPhaul M.J., and Gallo J.M. Ligand-dependent aggregation of polyglutamine-expanded androgen receptor in neuronal cells. Neuroreport 13 16 (2002) 2117-2120
18. Ellerby L.M., Hackam A.S., Propp S.S., Ellerby H.M., Rabizadeh S., Cashman N.R., Trifiro M.A., Pinsky L., Wellington C.L., Salvesen G.S., Hayden M.R., and Bredesen D.E. Kennedy's disease: caspase cleavage of the androgen receptor is a crucial event in cytotoxicity. J. Neurochem. 72 1 (1999) 185-195
19. Fernandez-Funez P., Nino-Rosales M.L., de Gouyon B., She W.C., Luchak J.M., Martinez P., Turiegano E., Benito J., Capovilla M., Skinner P.J., McCall A., Canal I., Orr H.T., Zoghbi H.Y., and Botas J. Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408 6808 (2000) 101-106
20. Fischbeck K.H. Kennedy disease. J. Inherit. Metab. Dis. 20 2 (1997) 152-158
21. Fischbeck K.H., Ionasescu V., Ritter A.W., Ionasescu R., Davies K., Ball S., Bosch P., Burns T., Hausmanowa-Petrusewicz I., Borkowska J., et al. Localization of the gene for X-linked spinal muscular atrophy. Neurology 36 12 (1986) 1595-1598
22. Forger N.G., Roberts S.L., Wong V., and Breedlove S.M. Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats. J. Neurosci. 13 11 (1993) 4720-4726
23. Freeman L.M., Watson N.V., and Breedlove S.M. Androgen spares androgen-insensitive motoneurons from apoptosis in the spinal nucleus of the bulbocavernosus in rats. Horm. Behav. 30 4 (1996) 424-433
24. Ishihara K., Yamagishi N., Saito Y., Adachi H., Kobayashi Y., Sobue G., Ohtsuka K., and Hatayama T. Hsp105alpha suppresses the aggregation of truncated androgen receptor with expanded CAG repeats and cell toxicity. J. Biol. Chem. 278 27 (2003) 25143-25150
25. Johansen J.A., Jordan C.L., and Breedlove S.M. Steroid hormone masculinization of neural structure in rats: a tale of two nuclei. Physiol. Behav. 83 2 (2004) 271-277
26. Katsuno M., Adachi H., Kume A., Li M., Nakagomi Y., Niwa H., Sang C., Kobayashi Y., Doyu M., and Sobue G. Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron 35 5 (2002) 843-854
27. Katsuno M., Sang C., Adachi H., Minamiyama M., Waza M., Tanaka F., Doyu M., and Sobue G. Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. Proc. Natl. Acad. Sci. U. S. A. 102 46 (2005) 16801-16806
28. Katsuno M., Adachi H., Minamiyama M., Waza M., Tokui K., Banno H., Suzuki K., Onoda Y., Tanaka F., Doyu M., and Sobue G. Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration. J. Neurosci. 26 47 (2006) 12106-12117
29. Katsuno M., Adachi H., Waza M., Banno H., Suzuki K., Tanaka F., Doyu M., and Sobue G. Pathogenesis, animal models and therapeutics in spinal and bulbar muscular atrophy (SBMA). Exp. Neurol. 200 1 (2006) 8-18
30. Kennedy W.R., Alter M., and Sung J.H. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology 18 7 (1968) 671-680
31. Kinirons P., and Rouleau G.A. Administration of testosterone results in reversible deterioration in Kennedy's disease. J. Neurol. Neurosurg. Psychiatry 79 1 (2008) 106-107
32. Kobayashi Y., Kume A., Li M., Doyu M., Hata M., Ohtsuka K., and Sobue G. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. J. Biol. Chem. 275 12 (2000) 8772-8778
33. La Spada A.R., Roling D.B., Harding A.E., Warner C.L., Spiegel R., Hausmanowa-Petrusewicz I., Yee W.C., and Fischbeck K.H. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nat. Genet. 2 4 (1992) 301-304
34. La Spada A.R., Wilson E.M., Lubahn D.B., Harding A.E., and Fischbeck K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352 6330 (1991) 77-79
35. La Spada A.R., Peterson K.R., Meadows S.A., McClain M.E., Jeng G., Chmelar R.S., Haugen H.A., Chen K., Singer M.J., Moore D., Trask B.J., Fischbeck K.H., Clegg C.H., and McKnight G.S. Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability. Hum. Mol. Genet. 7 6 (1998) 959-967
36. Lam Y.C., Bowman A.B., Jafar-Nejad P., Lim J., Richman R., Fryer J.D., Hyun E.D., Duvick L.A., Orr H.T., Botas J., and Zoghbi H.Y. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell 127 7 (2006) 1335-1347
37. Li M., Chevalier-Larsen E.S., Merry D.E., and Diamond M.I. Soluble androgen receptor oligomers underlie pathology in a mouse model of spinobulbar muscular atrophy. J. Biol. Chem. 282 5 (2007) 3157-3164
38. Lieberman A.P., Harmison G., Strand A.D., Olson J.M., and Fischbeck K.H. Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor. Hum. Mol. Genet. 11 17 (2002) 1967-1976
39. Mandrusiak L.M., Beitel L.K., Wang X., Scanlon T.C., Chevalier-Larsen E., Merry D.E., and Trifiro M.A. Transglutaminase potentiates ligand-dependent proteasome dysfunction induced by polyglutamine-expanded androgen receptor. Hum. Mol. Genet. 12 13 (2003) 1497-1506
40. McCampbell A., Taylor J.P., Taye A.A., Robitschek J., Li M., Walcott J., Merry D., Chai Y., Paulson H., Sobue G., and Fischbeck K.H. CREB-binding protein sequestration by expanded polyglutamine. Hum. Mol. Genet. 9 14 (2000) 2197-2202
41. McManamny P., Chy H.S., Finkelstein D.I., Craythorn R.G., Crack P.J., Kola I., Cheema S.S., Horne M.K., Wreford N.G., O'Bryan M.K., De Kretser D.M., and Morrison J.R. A mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 11 18 (2002) 2103-2111
42. Merry D.E., Kobayashi Y., Bailey C.K., Taye A.A., and Fischbeck K.H. Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy. Hum. Mol. Genet. 7 4 (1998) 693-701
43. Mifsud A., Sim C.K., Boettger-Tong H., Moreira S., Lamb D.J., Lipshultz L.I., and Yong E.L. Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility. Fertil. Steril. 75 2 (2001) 275-281
44. Minamiyama M., Katsuno M., Adachi H., Waza M., Sang C., Kobayashi Y., Tanaka F., Doyu M., Inukai A., and Sobue G. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 13 11 (2004) 1183-1192
45. Miniou P., Tiziano D., Frugier T., Roblot N., Le Meur M., and Melki J. Gene targeting restricted to mouse striated muscle lineage. Nucleic Acids Res. 27 19 (1999) e27
46. Monks D.A., Vanston C.M., and Watson N.V. Direct androgenic regulation of calcitonin gene-related peptide expression in motoneurons of rats with mosaic androgen insensitivity. J. Neurosci. 19 13 (1999) 5597-5601
47. Monks D.A., Getsios S., MacCalman C.D., and Watson N.V. N-cadherin is regulated by gonadal steroids in adult sexually dimorphic spinal motoneurons. J. Neurobiol. 47 4 (2001) 255-264
48. Monks D.A., O'Bryant E.L., and Jordan C.L. Androgen receptor immunoreactivity in skeletal muscle: enrichment at the neuromuscular junction. J. Comp. Neurol. 473 1 (2004) 59-72
49. Monks D.A., Kopachik W., Breedlove S.M., and Jordan C.L. Anabolic responsiveness of skeletal muscles correlates with androgen receptor protein but not mRNA. Can. J. Physiol. Pharm. 84 2 (2006) 273-277
50. Monks D.A., Johansen J.A., Mo K., Rao P.R., Eagleson B., Yu Z., Lieberman A.P., Breedlove S.M., and Jordan C.L. Lieberman, A.P., Breedlove, S.M., and Jordan, C.L., in press. Overexpression of wildtype androgen receptor in muscle recapitulates polyglutamine disease. Proc. Natl. Acad. Sci. U. S. A. 104 46 (2007) 18259-18264
51. Morfini G., Pigino G., Szebenyi G., You Y., Pollema S., and Brady S.T. JNK mediates pathogenic effects of polyglutamine-expanded androgen receptor on fast axonal transport. Nat. Neurosci. 9 7 (2006) 907-916
52. Morris J.A., Jordan C.L., and Breedlove S.M. Sexual differentiation of the vertebrate nervous system. Nat. Neurosci. 7 10 (2004) 1034-1039
53. Nagashima T., Seko K., Hirose K., Mannen T., Yoshimura S., Arima R., Nagashima K., and Morimatsu Y. Familial bulbo-spinal muscular atrophy associated with testicular atrophy and sensory neuropathy (Kennedy-Alter-Sung syndrome). Autopsy case report of two brothers. J. Neurol. Sci. 87 2-3 (1988) 141-152
54. Nakajima H., Kimura F., Nakagawa T., Ikemoto T., Furutama D., Shinoda K., Kato S., Shimizu A., and Ohsawa N. Effects of androgen receptor polyglutamine tract expansion on proliferation of NG108-15 cells. Neurosci. Lett. 222 2 (1997) 83-86
55. Palazzolo I., Burnett B.G., Young J.E., Brenne P.L., La Spada A.R., Fischbeck K.H., Howell B.W., and Pennuto M. Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity. Hum. Mol. Genet 16 13 (2007) 1593-1603
56. Rand M.N., and Breedlove S.M. Androgen alters the dendritic arbors of SNB motoneurons by acting upon their target muscles. J. Neurosci. 15 6 (1995) 4408-4416
57. Sengelaub D.R., Jordan C.L., Kurz E.M., and Arnold A.P. Hormonal control of neuron number in sexually dimorphic spinal nuclei of the rat: II. Development of the spinal nucleus of the bulbocavernosus in androgen-insensitive (Tfm) rats. J. Comp. Neurol. 280 4 (1989) 630-636
58. Sobue G., Hashizume Y., Mukai E., Hirayama M., Mitsuma T., and Takahashi A. X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain 112 Pt 1 (1989) 209-232
59. Sopher B.L., Thomas Jr. P.S., LaFevre-Bernt M.A., Holm I.E., Wilke S.A., Ware C.B., Jin L.W., Libby R.T., Ellerby L.M., and La Spada A.R. Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration. Neuron 41 5 (2004) 687-699
60. Stenoien D.L., Cummings C.J., Adams H.P., Mancini M.G., Patel K., DeMartino G.N., Marcelli M., Weigel N.L., and Mancini M.A. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum. Mol. Genet. 8 5 (1999) 731-741
61. Takeshita Y., Fujinaga R., Zhao C., Yanai A., and Shinoda K. Huntingtin-associated protein 1 (HAP1) interacts with androgen receptor (AR) and suppresses SBMA-mutant-AR-induced apoptosis. Hum. Mol. Genet. 15 15 (2006) 2298-2312
62. Takeyama K., Ito S., Yamamoto A., Tanimoto H., Furutani T., Kanuka H., Miura M., Tabata T., and Kato S. Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila. Neuron 35 5 (2002) 855-864
63. Tan J.A., Joseph D.R., Quarmby V.E., Lubahn D.B., Sar M., French F.S., and Wilson E.M. The rat androgen receptor: primary structure, autoregulation of its messenger ribonucleic acid, and immunocytochemical localization of the receptor protein. Mol. Endocrinol. 2 12 (1988) 1276-1285
64. Thomas M., Dadgar N., Aphale A., Harrell J.M., Kunkel R., Pratt W.B., and Lieberman A.P. Androgen receptor acetylation site mutations cause trafficking defects, misfolding, and aggregation similar to expanded glutamine tracts. J. Biol. Chem. 279 9 (2004) 8389-8395
65. Thomas M., Harrell J.M., Morishima Y., Peng H.M., Pratt W.B., and Lieberman A.P. Pharmacologic and genetic inhibition of hsp90-dependent trafficking reduces aggregation and promotes degradation of the expanded glutamine androgen receptor without stress protein induction. Hum. Mol. Genet. 15 11 (2006) 1876-1883
66. Thomas Jr. P.S., Fraley G.S., Damian V., Woodke L.B., Zapata F., Sopher B.L., Plymate S.R., and La Spada A.R. Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy. Hum. Mol. Genet. 15 14 (2006) 2225-2238
67. Tsuda H., Jafar-Nejad H., Patel A.J., Sun Y., Chen H.K., Rose M.F., Venken K.J., Botas J., Orr H.T., Bellen H.J., and Zoghbi H.Y. The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/senseless proteins. Cell 122 4 (2005) 633-644
68. Walcott J.L., and Merry D.E. Ligand promotes intranuclear inclusions in a novel cell model of spinal and bulbar muscular atrophy. J. Biol. Chem. 277 52 (2002) 50855-50859
69. Watson N.V., Freeman L.M., and Breedlove S.M. Neuronal size in the spinal nucleus of the bulbocavernosus: direct modulation by androgen in rats with mosaic androgen insensitivity. J. Neurosci. 21 3 (2001) 1062-1066
70. Waza M., Adachi H., Katsuno M., Minamiyama M., Sang C., Tanaka F., Inukai A., Doyu M., and Sobue G. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat. Med. 11 10 (2005) 1088-1095
71. Yang W., Dunlap J.R., Andrews R.B., and Wetzel R. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum. Mol. Genet. 11 23 (2002) 2905-2917
72. Yang Z., Chang Y.J., Yu I.C., Yeh S., Wu C.C., Miyamoto H., Merry D.E., Sobue G., Chen L.M., Chang S.S., and Chang C. ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat. Med. 13 3 (2007) 348-353
73. Yarbrough W.G., Quarmby V.E., Simental J.A., Joseph D.R., Sar M., Lubahn D.B., Olsen K.L., French F.S., and Wilson E.M. A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat. J. Biol. Chem. 265 15 (1990) 8893-8900
74. Yu Z., Dadgar N., Albertelli M., Gruis K., Jordan C., Robins D.M., and Lieberman A.P. Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model. J. Clin. Invest. 116 10 (2006) 2663-2672
75. Yu Z., Dadgar N., Albertelli M., Scheller A., Albin R.L., Robins D.M., and Lieberman A.P. Abnormalities of germ cell maturation and sertoli cell cytoskeleton in androgen receptor 113 CAG knock-in mice reveal toxic effects of the mutant protein. Am. J. Pathol. 168 1 (2006) 195-204
76. Zoghbi H.Y., and Orr H.T. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23 (2000) 217-247