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Androgen Resistance

  • Living reference work entry
  • First Online:
Endocrinology of the Testis and Male Reproduction

Part of the book series: Endocrinology ((ENDOCR))

  • 262 Accesses

Abstract

Androgen insensitivity arises from target tissue resistance to androgens. Androgen insensitivity syndrome (AIS) is the most common specific etiology of 46,XY disorder of sex development. It is a result of the failure of androgens to act via the androgen receptor. The phenotype is variable, from female phenotype in complete AIS to male phenotype with gynecomastia or infertility in minimal AIS, depending on the residual androgen receptor activity.

More than 400 different androgen receptor mutations have been reported and they have been identified in all eight exons of the gene. The treatment consists of counseling, psychosocial support, endocrine therapy, and surgery. Both hormonal substitution and timing of surgery are still controversial.

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References

  • Adachi M, Takayanagi R, Tomura A, Imasaki K, Kato S, Goto K, Yanase T, Ikuyama S, Nawata H. Androgen-insensitivity syndrome as a possible coactivator disease. N Engl J Med. 2000;343:856–62.

    Article  CAS  PubMed  Google Scholar 

  • Ahmed SF, Cheng A, Hughes IA. Assessment of the gonadotropin-gonadal axis in androgen insensitivity syndrome. Arch Dis Child. 1999;80:324–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J, Shimura N, Tait AD, Hughes IA. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000a;85:658–65.

    CAS  PubMed  Google Scholar 

  • Ahmed SF, Khwaja O, Hughes IA. The role of a clinical score in the assessment of ambiguous genitalia. BJU Int. 2000b;85:120–4.

    Article  CAS  PubMed  Google Scholar 

  • Akinloye O, Gromoll J, Nieschlag E, Simoni M. Androgen receptor gene CAG and GGN polymorphisms in infertile Nigerian men. J Endocrinol Investig. 2009;32:797–804.

    Article  CAS  Google Scholar 

  • Andersson S, Berman DM, Jenkins EP, Russell DW. Deletion of steroid 5alfa-reductase 2 gene in male pseudohermaphroditism. Nature. 1991;354:159–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrew SE, Goldberg YP, Hayden MR. Rethinking genotype and phenotype correlations in polyglutamine expansion disorders. Hum Mol Genet. 1997;6:2005–10.

    Article  CAS  PubMed  Google Scholar 

  • Bangsbøll S, Qvist I, Lebech PE, Lewinsky M. Testicular feminization syndrome and associated gonadal tumours in Denmark. Acta Obstet Gynecol Scand. 1992;71:63–6.

    Article  PubMed  Google Scholar 

  • Batch JA, Davies HR, Evans BA, Hughes IA, Patterson MN. Phenotypic variation and detection of carrier status in the partial androgen insensitivity syndrome. Arch Dis Child. 1993;68:453–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertelloni S, Baroncelli GI, Federico G, Cappa M, Lala R, Saggese G. Altered bone mineral density in patients with complete androgen insensitivity syndrome. Horm Res. 1998;50:309–14.

    Article  CAS  PubMed  Google Scholar 

  • Boehmer AL, Brinkmann AO, Nijman RM, Verleun-Mooijman MC, de Ruiter P, Niermeijer MF, Drop SL. Genotype versus phenotype in families with androgen insensitivity syndrome. J Clin Endocrinol Metab. 2001;86:4151–60.

    Article  CAS  PubMed  Google Scholar 

  • Bouvattier C, Carel JC, Lecointre C, David A, Sultan C, Bertrand AM, Morel Y, Chaussain JL. Postnatal changes of T, LH, and FSH in 46,XY infants with mutations in the AR gene. J Clin Endocrinol Metab. 2002;87:29–32.

    Article  CAS  PubMed  Google Scholar 

  • Brinkmann AO. Molecular basis of androgen insensitivity. Mol Cell Endocrinol. 2001;179:105–9.

    Article  CAS  PubMed  Google Scholar 

  • Brockschmidt FF, Nothen MM, Hillmer AM. The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function. J Mol Endocrinol. 2007;39:1–8.

    Article  CAS  PubMed  Google Scholar 

  • Brown TR, Lubahn DB, Wilson EM, Joseph DR, French FS, Migeon CJ. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: evidence for further genetic heterogeneity of this syndrome. Proc Natl Acad Sci USA. 1988;85:8151–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS, Willard HF. Androgen receptor locus on human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet. 1989;44:264–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brunner F, Fliegner M, Krupp K, Rall K, Brucker S, Richter-Appelt H. Gender role, gender identity and sexual orientation in CAIS (“XY-women”) compared with subfertile and infertile 46,XX woman. J Sex Res. 2016;53:109–24.

    Article  PubMed  Google Scholar 

  • Burnstein S, Grumbach MM, Kaplan S. Early determination of androgen responsiveness is important in the management of microphallus. Lancet. 1979;2:983–6.

    Article  Google Scholar 

  • Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res. 1994;22:3181–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang C, Kokontis J, Liao S. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science. 1988;240:324–6.

    Article  CAS  PubMed  Google Scholar 

  • Chu J, Zhang R, Zhao Z, Zou W, Han Y, Qi Q, Zhang H, Wang JC, Tao S, Liu X, Luo Z. Male fertility is compatible with an Arg840Cys substitution in the AR in a large Chinese family affected with divergent phenotypes of AR insensitivity syndrome. J Clin Endocrinol Metab. 2002;87:347–51.

    Article  CAS  PubMed  Google Scholar 

  • Collaer ML, Hines M. Human behavioural sex differences: a role for gonadal hormones during early development. Psch Bull. 1995;118:55–107.

    Article  CAS  Google Scholar 

  • Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev. 2006;27:468–84.

    Article  CAS  PubMed  Google Scholar 

  • Coutant R, Mallet D, Lahlou N, Bouhours-Nouet N, Guichet A, Coupris L, Croue A, Morel Y. Heterozygous mutation of steroidogenic factor-1 in 46,XY subjects may mimic partial androgen insensitivity syndrome. J Clin Endocrinol Metab. 2007;92:2868–73.

    Article  CAS  PubMed  Google Scholar 

  • Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab. 2007;92:4319–26.

    Article  CAS  PubMed  Google Scholar 

  • Deans R, Creighton SM, Liao LM, Conway GS. Timing of gonadectomy in adult women with complete androgen insensitivity syndrome (CAIS): patient preferences and clinical evidence. Clin Endocrinol. 2012;76:894–8.

    Article  Google Scholar 

  • Dieffenbach H. Familiaerer hermaphroditismus. Inaugural dissertation. Stuttgart. 1912.

    Google Scholar 

  • Estébanez-Perpiñá E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ. A surface on the androgen receptor that allosterically regulates coactivators binding. Proc Natl Acad Sci USA. 2007;10:16074–9.

    Article  Google Scholar 

  • Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988;240:889–95.

    Article  CAS  PubMed  Google Scholar 

  • Farla P, Hersmus R, Geverts B, Mari PO, Nigg AL, Dubbink HJ, Trapman J, Houtsmuller AB. The androgen receptor ligand-binding domain stabilizes DNA binding in living cells. J Struct Biol. 2004;147:50–61.

    Article  CAS  PubMed  Google Scholar 

  • Ghali SA, Gottlieb B, Lumbroso R, Beitel LK, Elhaji Y, Wu J, Pinsky L, Trifiro MA. The use of androgen receptor amino/carboxyl-terminal interaction assays to investigate androgen receptor gene mutations in subjects with varying degrees of androgen insensitivity. J Clin Endocrinol Metab. 2003;88:2185–93.

    Article  CAS  PubMed  Google Scholar 

  • Giwercman A, Kledal T, Schwartz M, Giwercman YL, Leffers H, Zazzi H, Wedell A, Skakkebaek NE. Preserved male fertility despite decreased androgen sensitivity caused by a mutation in the ligand-binding domain of the androgen receptor. J Clin Endocrinol Metab. 2000;85:2253–9.

    Google Scholar 

  • Gottlieb B, Beitel LK, Nadarajah A, Palioura M, Trifiro M. The androgen receptor gene mutations database(ARDB): 2012 update. Hum Mutat. 2012;33:887–94.

    Article  CAS  PubMed  Google Scholar 

  • Griffin JE, Punyashthiti K, Wilson JD. Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance. J Clin Invest. 1976;57:1342–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hannema SE, Scott IS, Hodapp J, Martin H, Coleman N, Schwabe JW, Hughes IA. Residual activity of mutant androgen receptors explains wolffian duct development in the complete androgen insensitivity syndrome. J Clin Endocrinol Metab. 2004;89:5815–22.

    Article  CAS  PubMed  Google Scholar 

  • Hannema SE, Scott IS, Rajpert-De Meyts E, Skakkebaek NE, Coleman N, Hughes IA. Testicular development in the complete androgen insensitivity syndrome. J Pathol. 2006;208:518–27.

    Article  CAS  PubMed  Google Scholar 

  • He B, Kemppainen JA, Wilson EM. FXXLF and WXXLF sequences mediate the NH2-terminal interaction with the ligand binding domain of the androgen receptor. J Biol Chem. 2000;275:22986–94.

    Article  CAS  PubMed  Google Scholar 

  • He B, Gampe Jr RT, Hnat AT, Faggart JL, Minges JT, French FS, Wilson EM. Probing the functional link between androgen receptor coactivator and ligand-binding sites in prostate cancer and androgen insensitivity. J Biol Chem. 2006;281:6648–63.

    Article  CAS  PubMed  Google Scholar 

  • Hellmann P, Christiansen P, Johannsen TH, Main KM, Duno M, Juul A. Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia. Arch Dis Child. 2012;97:403–9.

    Article  PubMed  Google Scholar 

  • Helsen C, Dubois V, Verfaillie A, Young J, Trekels M, Vancraenenbroeck R, De Maeyer M, Claessens F. Evidence for DNA-binding domain--ligand-binding domain communications in the androgen receptor. Mol Cell Biol. 2012;32:3033–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiort O, Willenbring H, Albers N, Hecker W, Engert J, Dibbelt L, Sinnecker GH. Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency. Eur J Ped. 1996;155:445–51.

    Article  CAS  Google Scholar 

  • Hiort O, Sinnecker GH, Holterhus PM, Nitsche EM, Kruse K. Inherited and de novo androgen receptor gene mutations: investigation of single-case families. J Pediatr. 1998;132:939–43.

    Article  CAS  PubMed  Google Scholar 

  • Hiort O, Birnbaum W, Marshall L, Wünsch L, Werner R, Schröder T, Döhnert U, Holterhus PM. Management of disorders of sex development. Nat Rev Endocrinol. 2014;10:520–9.

    Article  PubMed  Google Scholar 

  • Holterhus PM, Brüggenwirth HT, Hiort O, Kleinkauf-Houcken A, Kruse K, Sinnecker GH, Brinkmann AO. Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome. J Clin Endocrinol Metab. 1997;82:3584–9.

    CAS  PubMed  Google Scholar 

  • Holterhus PM, Deppe U, Werner R, Richter-Unruh A, Bebermeier JH, Wünsch L, Krege S, Schweikert HU, Demeter J, Riepe F, Hiort O, Brooks JD. Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome. BMC Genomics. 2007;8:376.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang G, Shan W, Zeng L, Huang L. Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias: results from a meta-analysis. Genet Mol Res. 2015;6(14):1580–8.

    Article  CAS  Google Scholar 

  • Hughes IA, Houk C, Ahmed SF, Lee PA, Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group. Consensus statement on management of intersex disorders. J Pediatr Urol. 2006;2:148–62.

    Article  CAS  PubMed  Google Scholar 

  • Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J. Androgen insensitivity syndrome. Lancet. 2012;380:1419–28.

    Article  CAS  PubMed  Google Scholar 

  • Huhtaniemi IT, Pye SR, Limer KL, Thomson W, O’Neill TW, Platt H, Payne D, John SL, Jiang M, Boonen S, Borghs H, Vanderschueren D, Adams JE, Ward KA, Bartfai G, Casanueva F, Finn JD, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Silman AJ, Wu FC, European Male Ageing Study Group. Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats. J Clin Endocrinol Metab. 2009;94:277–84.

    Article  CAS  PubMed  Google Scholar 

  • Hurme T, Lahdes-Vasama T, Mäkela E, Iber T, Toppari J. Clinical findings in prepubertal girls with inguinal hernia with special reference to the diagnosis of androgen insensitivity syndrome. Scand J Urol Nephrol. 2009;43:42–6.

    Article  CAS  PubMed  Google Scholar 

  • Hurt WG, Bodurtha JN, McCall JB, Ali MM. Seminoma in pubertal patient with androgen insensitivity syndrome. Am J Obstet Gynecol. 1989;161:530–1.

    Article  CAS  PubMed  Google Scholar 

  • Hutson JM, Li R, Southwell BR, Newgreen D, Cousinery M. Regulation of testicular descent. Pediatr Surg Int. 2015;31:317–25.

    Article  PubMed  Google Scholar 

  • Imperato-McGinley J, Sanchez RS, Spencer JR, Yee B, Vaughan ED. Comparison of the effects of the 5alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies. Endocrinology. 1992;131:1149–56.

    Article  CAS  PubMed  Google Scholar 

  • Jääskeläinen J. Molecular biology of androgen insensitivity. Mol Cell Endocrinol. 2012;16(352):4–12.

    Article  CAS  Google Scholar 

  • Jääskeläinen J, Deeb A, Schwabe JW, Mongan NP, Martin H, Hughes IA. Human androgen receptor gene ligand-binding-domain mutations leading to disrupted interaction between the N- and C-terminal domains. J Mol Endocrinol. 2006;36:361–8.

    Article  PubMed  CAS  Google Scholar 

  • Jagiello G, Atwell J. Prevalence of testicular feminization. Lancet. 1962;279:329.

    Article  Google Scholar 

  • Josso N, Boussin L, Knebelmann B, Nihoul-Fékété C, Picard JY. Anti-Mullerian hormone and intersex states. Trends Endocrinol Metab. 1991;2:227–33.

    Article  CAS  PubMed  Google Scholar 

  • Kaufman M, Pinsky L, Gottlieb B, Schweitzer M, Brezezinski A, von Westarp C, Ginsberg J. Androgen receptor defects in patients with minimal and partial androgen resistance classified according to a model of androgen-receptor complex energy states. Horm Res. 1990;33:87–94.

    Article  CAS  PubMed  Google Scholar 

  • Keenan BS, Meyer WJ, Hadjian AJ, Migeon CJ. Androgen receptor in human skin fibroblasts. Characterization of a specific 17beta-hydroxy-5alpha-androstan-3-one-protein complex in cell sonicates and nuclei. Steroids. 1975;25:535–52.

    Article  CAS  PubMed  Google Scholar 

  • Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, van Reen M, et al. Male pseudohermafroditism due to a homozygous missense mutation of the luteinizing hormone receptor. Nature Genet. 1995;9:160–4.

    Article  CAS  PubMed  Google Scholar 

  • La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991;352:77–9.

    Article  CAS  PubMed  Google Scholar 

  • Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee YS, Kirk JM, Stanhope RG, Johnston DI, Harland S, Auchus RJ, Andersson S, Hughes IA. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol. 2007;67:20–8.

    Article  CAS  Google Scholar 

  • Lek N, Miles H, Bunch T, Pilfold-Wilkie V, Tadokoro-Cuccaro R, Davies J, Ong KK, Hughes IA. Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction. Arch Dis Child. 2014;99:358–61.

    Article  PubMed  Google Scholar 

  • Lim HN, Nixon RM, Chen H, Hughes IA, Hawkins JR. Evidence that longer androgen receptor polyglutamine repeats are a causal factor for genital abnormalities. J Clin Endocrinol Metab. 2001;86:3207–10.

    Article  CAS  PubMed  Google Scholar 

  • Lin D, Sugawara T, Strauss 3rd JF, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL. Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science. 1995;267:1828–31.

    Article  CAS  PubMed  Google Scholar 

  • Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM. Cloning of human androgen receptor complementary DNA and localization to the X-chromosome. Science. 1988;240:327–30.

    Article  CAS  PubMed  Google Scholar 

  • Lucas-Herald A, Bertelloni S, Juul A, Bryce J, Jiang J, Rodie M, et al. The long term outcome of boys with partial androgen insensitivity syndrome and a mutation in the androgen receptor gene. J Clin Endocrinol Metab. 2016;101(11):3959–67. [Epub ahead of print].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lumbroso R, Beitel LK, Vasiliou DM, Trifiro MA, Pinsky L. Codon-usage variants in the polymorphic (GGN)n trinucleotide repeat of the human androgen receptor gene. Hum Genet. 1999;101:43–6.

    Article  Google Scholar 

  • Lundin KB, Giwercman YL, Rylander L, Hagmar L, Giwercman A. Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men. Eur J Endocrinol. 2006;155:347–54.

    Article  CAS  PubMed  Google Scholar 

  • Lundin KB, Giwercman A, Dizeyi N, Giwercman Y. Functional in vitro characterisation of the androgen receptor GGN polymorphism. Mol Cell Endocrinol. 2007;264:184–7.

    Article  CAS  PubMed  Google Scholar 

  • Manuel M, Katayama KP, Jones Jr HW. The age of occurrence of gonadal tumors in intersex patients with a Y chromosome. Br Med J. 1976;288:1419–20.

    Google Scholar 

  • Marcus R, Leary D, Schneider DL, Shane E, Favus M, Quigley CA. The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000;85:1032–7.

    Article  CAS  PubMed  Google Scholar 

  • Melo KF, Mendonca BB, Billerbeck AE, Costa EM, Inácio M, Silva FA, Leal AM, Latronico AC, Arnhold IJ. Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: five novel mutations in the androgen receptor gene. J Clin Endocrinol Metab. 2003;88:3241–50.

    Article  CAS  PubMed  Google Scholar 

  • Migeon CJ, Brown TR, Lanes R, Palacios A, Amrhein JA, Schoen EJ. A clinical syndrome of mild androgen insensitivity. J Clin Endocrinol Metab. 1984;59:672–8.

    Article  CAS  PubMed  Google Scholar 

  • Miles HL, Gidlöf S, Nordenström A, Ong KK, Hughes IA. The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling. Arch Dis Child Fetal Neonatal Ed. 2010;95(6):F435–8.

    Google Scholar 

  • Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen insensitivity syndrome. Best Pract Res Clin Endocrinol Metab. 2015;29:569–80.

    Article  CAS  PubMed  Google Scholar 

  • Morris JM. The syndrome of testicular feminization in male pseudohermafrodites. Am J Obstet Gynecol. 1953;65:1192–211.

    Article  CAS  PubMed  Google Scholar 

  • Muñoz-Torres M, Jódar E, Quesada M, Escobar-Jiménez F. Bone mass in androgen-insensitivity syndrome: response to hormonal replacement therapy. Calcif Tissue Int. 1995;57:94–6.

    Article  PubMed  Google Scholar 

  • Nakhal RS, Hall-Craggs M, Freeman A, Kirkham A, Conway GS, Arora R, Woodhouse CR, Wood DN, Creighton SM. Evaluation of retained testes in adolescent girls and women with complete androgen insensitivity syndrome. Radiology. 2013;268:153–60.

    Article  PubMed  Google Scholar 

  • Nation TR, Buraundi S, Balic A, Farmer PJ, Newgreen D, Southwell BR, Hutson JM. The effect of flutamide on expression of androgen and estrogen receptors in the gubernaculum and surrounding structures during testicular descent. J Pediatr Surg. 2011;46:2358–62.

    Article  PubMed  Google Scholar 

  • Nef S, Parada LF. Cryptorchidism in mice mutant for Insl3. Nat Genet. 1999;22:295–9.

    Article  CAS  PubMed  Google Scholar 

  • Nenonen H, Bjork C, Skjaerpe PA, Giwercman A, Rylander L, Svartberg J, Giwercman YL. CAG repeat number is not inversely associated with androgen receptor activity in vitro. Mol Hum Reprod. 2010;16:153–7.

    Article  CAS  PubMed  Google Scholar 

  • Nenonen HA, Giwercman A, Hallengren E, Giwercman YL. Non-linear association between androgen receptor CAG repeat length and risk of male subfertility - a meta-analysis. Int J Androl. 2011;34:327–32.

    Article  CAS  PubMed  Google Scholar 

  • New MI, Nimkarn S, Brandon DD, Cunningham-Rundles S, Wilson RC, Newfield RS, Vandermeulen J, Barron N, Russo C, Loriaux DL, O’Malley B. Resistance to multiple steroids in two sisters. J Steroid Biochem Mol Biol. 2001;76:161–6.

    Article  CAS  PubMed  Google Scholar 

  • Nichols JL, Bieber EJ, Gell JS. Case of sisters with complete androgen insensitivity syndrome and discordant Mullerian remnants. Fertil Steril. 2009;91(932):e15–8.

    Google Scholar 

  • Ong YC, Wong HB, Adaikan G, Yong EL. Directed pharmacological therapy of ambiguous genitalia due to an androgen receptor gene mutation. Lancet. 1999;354:1444–5.

    Article  CAS  PubMed  Google Scholar 

  • Pan B, Li R, Chen Y, Tang Q, Wu W, Chen L, Lu C, Pan F, Ding H, Xia Y, Hu L, Chen D, Sha J, Wang X. Genetic association between androgen receptor gene CAG repeat length polymorphism and male infertility: a meta-analysis. Medicine (Baltimore). 2016;95:e2878.

    Article  CAS  Google Scholar 

  • Patel V, Casey RK, Gomez-Lobo V. Timing of gonadectomy in patients with complete androgen insensitivity syndrome-current recommendations and future directions. J Pediatr Adolesc Gynecol. 2016;29:320–5.

    Article  PubMed  Google Scholar 

  • Pereira de Jésus-Tran K, Côté PL, Cantin L, Blanchet J, Labrie F, Breton R. Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity. Protein Sci. 2006;15:987–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pergament E, Heimler A, Shah P. Testicular feminisation and inguinal hernia. Lancet. 1973;2:740–1.

    Article  CAS  PubMed  Google Scholar 

  • Pettersson G, Bonnier G. Inherited sex-mosaic in man. Hereditas. 1937;23:49–69.

    Article  Google Scholar 

  • Philibert P, Audran F, Pienkowski C, Morange I, Kohler B, Flori E, Heinrich C, Dacou-Voutetakis C, Joseph MG, Guedj AM, Journel H, Hecart-Bruna AC, Khotchali I, Ten S, Bouchard P, Paris F, Sultan C. Complete androgen insensitivity syndrome is frequently due to premature stop codons in exon 1 of the androgen receptor gene: an international collaborative report of 13 new mutations. Fertil Steril. 2010;94:472–6.

    Article  CAS  PubMed  Google Scholar 

  • Pinsky L, Kaufman M, Killinger DW, Burko B, Shatz D, Volpé R. Human minimal androgen insensitivity with normal dihydrotestosterone-binding capacity in cultured genital skin fibroblasts: evidence for an androgen-selective qualitative abnormality of the receptor. Am J Hum Genet. 1984;36:965–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pinsky L, Kaufman K, Killinger DW. Impaired spermatogenesis is not an obligate expression of receptor-defective androgen resistance. Am J Med Genet. 1989;32:100–4.

    Article  CAS  PubMed  Google Scholar 

  • Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev. 1995;16:271–321.

    CAS  PubMed  Google Scholar 

  • Rajender S, Rajani V, Gupta NJ, Chakravarty B, Singh L, Thangaraj K. No association of androgen receptor GGN repeat length polymorphism with infertility in Indian men. J Androl. 2008;27:785–9.

    Article  CAS  Google Scholar 

  • Rhéaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F. Structure and expression of a ne complimentary DNA encoding the almost exclusive 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase in human adrenal and gonads. Mol Endocrinol. 1991;5:1147–57.

    Article  PubMed  Google Scholar 

  • Saez JM, De Peretti E, Morera AM, David M, Bertrand J. Familial male pseudohermaphroditism with gynaecomastia due to testicular 17-ketosteroid reductase defect. 1. Studies in vivo. J Clin Endocrinol Metab. 1971;32:604–10.

    Article  CAS  PubMed  Google Scholar 

  • Sinnecker GH, Hiort O, Nitsche EM, Holterhus PM, Kruse K. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene German Collaborative Intersex Study Group. Eur J Ped. 1997;156:7–14.

    Article  CAS  Google Scholar 

  • Sobel V, Schwartz B, Zhu YS, Cordero JJ, Imperato-McGinley J. Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes. J Clin Endocrinol Metab. 2006;91(8):3017–23.

    Article  CAS  PubMed  Google Scholar 

  • Soule SG, Conway G, Prelevic GM, Prentice M, Ginsburg J, Jacobs HS. Osteopenia as a feature of the androgen insensitivity syndrome. Clin Endocrinol. 1995;43:671–5.

    Article  CAS  Google Scholar 

  • Southern AL. The syndrome of testicular feminization: a report of three cases with chromatographic analysis of the urinary neutral 17-ketosteroids. Ann Intern Med. 1961;55:925–31.

    Article  Google Scholar 

  • Tahiri B, Auzou G, Nicolas JC, Sultan C, Lupo B. Participation of critical residues from the extreme C-terminal end of the human androgen receptor in the ligand binding function. Biochemistry. 2001;40:8431–7.

    Article  CAS  PubMed  Google Scholar 

  • Thompson J, Saatcioglu F, Jänne OA, Palvimo JJ. Disrupted amino- and carboxyl-terminal interactions of the androgen receptor are linked to androgen insensitivity. Mol Endocrinol. 2001;15:923–35.

    Article  CAS  PubMed  Google Scholar 

  • Thyen U, Lanz K, Holterhus PM, Hiort O. Epidemiology and initial management of ambiguous genitalia at birth in Germany. Horm Res. 2006;66:195–203.

    CAS  PubMed  Google Scholar 

  • Tordjman KM, Yaron M, Berkovitz A, Botchan A, Sultan C, Lumbroso S. Fertility after high-dose testosterone and intracytoplasmic sperm injection in a patient with androgen insensitivity syndrome with a previously unreported androgen receptor mutation. Andrologia. 2014;46:703–6.

    Article  CAS  PubMed  Google Scholar 

  • Tremblay RR, Foley Jr TP, Corvol P, Park IJ, Kowarski A, Blizzard RM, Jones Jr HW, Migeon CJ. Plasma concentration of testosterone, dihydrotestosterone, testosterone-oestradiol binding globulin, and pituitary gonadotrophins in the syndrome of male pseudo-hermaphroditism with testicular feminization. Acta Endocrinol. 1972;70:331–41.

    CAS  PubMed  Google Scholar 

  • Varrela J, Alvesalo L, Vinkka H. Body size and shape in 46, XY females with complete testicular feminization. Ann Hum Biol. 1984;11:291–301.

    Article  CAS  PubMed  Google Scholar 

  • Viner RM, Teoh Y, Williams DM, Patterson MN, Hughes IA. Androgen insensitivity syndrome: a survey of diagnostic procedures and management in the UK. Arch Dis Child. 1997;77:305–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Werner R, Holterhus PM, Binder G, Schwarz HP, Morlot M, Struve D, Marschke C, Hiort O. The A645D mutation in the hinge region of the human androgen receptor (AR) gene modulates AR activity, depending on the context of the polymorphic glutamine and glycine repeats. J Clin Endocrinol Metab. 2006;91:3515–20.

    Article  CAS  PubMed  Google Scholar 

  • Werner R, Grotsch H, Hiort O. 46,XY disorders of sex development – the undermasculinised male with disorders of androgen action. Best Pract Res Clin Endocrinol Metab. 2010;24:263–77.

    Article  CAS  PubMed  Google Scholar 

  • Wilkins L. Heterosexual development. In: Thomas CC, editor. The diagnosis and treatment of endocrine disorders in childhood and adolescence. Springfield, IL; 1950. p. 256–79.

    Google Scholar 

  • Wilson JD, Griffin JE, Russell DW. Steroid 5alpha-reductase deficiency. Endocr Rev. 1993;14:577–93.

    CAS  PubMed  Google Scholar 

  • Wisniewski AB, Migeon CJ, Meyer-Bahlburg HF, Gearhart JP, Berkovitz GD, Brown TR, Money J. Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. J Clin Endocrinol Metab. 2000;85:2664–9.

    CAS  PubMed  Google Scholar 

  • Yanase T, Simpson ER, Waterman MR. 17alfa-hydroxylase/17,20-lyase deficiency: from clinical investigation to molecular definition. Endocr Rev. 1991;12:91–108.

    Article  CAS  PubMed  Google Scholar 

  • Zachmann M, Prader A, Sobel EH, Crigler Jr JF, Ritzén EM, Atarés M, Ferrandez A. Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls. J Pediatr. 1986;108:694–7.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Clinical Medicine, Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland, PO Box 100, 70029 KUH, Kuopio, Finland

    Jarmo Jääskeläinen

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  1. Jarmo Jääskeläinen
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Correspondence to Jarmo Jääskeläinen .

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  1. Dept. of Biomedicine, Metabolism and Neural Sciences, University of Modena and Reggio Emilia, Modena, Modena, Italy

    Manuela Simoni

  2. Dept. of Surgery and Cancer, Imperial College London, London, United Kingdom

    Ilpo Huhtaniemi

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Jääskeläinen, J. (2016). Androgen Resistance. In: Simoni, M., Huhtaniemi, I. (eds) Endocrinology of the Testis and Male Reproduction. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-29456-8_26-1

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  • DOI: https://doi.org/10.1007/978-3-319-29456-8_26-1

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