Best Practice & Research Clinical Endocrinology & Metabolism
Volume 24, Issue 2 , Pages 263-277 , April 2010

46,XY disorders of sex development – the undermasculinised male with disorders of androgen action

References 

  1. Brinkmann AO, Faber PW, van Rooij HC, et al. The human androgen receptor: domain structure, genomic organisation and regulation of expression. J Steroid Biochem. 1989;34:307–310b.Siiteri PK, Wilson JD. Testosterone formation and metabolism during male sexual differentiation in the human embryo. The Journal of Clinical Endocrinology and Metabolism. 1974;38(1):113–125
  2. Sajjad Y, Quenby SM, Nickson P, et al. Expression of androgen receptors in upper human fetal reproductive tract. Human Reproduction (Oxford, England). 2004;19(7):1659–1665
  3. Rey R, Picard JY. Embryology and endocrinology of genital development. Baillière’s Clinical Endocrinology and Metabolism. 1998;12(1):17–33
  4. Marker PC, Donjacour AA, Dahiya R, et al. Hormonal, cellular, and molecular control of prostatic development. Developmental Biology. 2003;253(2):165–174
  5. Ellsworth K, Harris G. Expression of the type 1 and 2 steroid 5 alpha-reductases in human fetal tissues. Biochemical and Biophysical Research Communications. 1995;215(2):774–780
  6. Deslypere JP, Young M, Wilson JD, et al. Testosterone and 5 alpha-dihydrotestosterone interact differently with the androgen receptor to enhance transcription of the MMTV-CAT reporter gene. Molecular and Cellular Endocrinology. 1992;88(1–3):15–22
  7. Adams JY, Leav I, Lau KM, et al. Expression of estrogen receptor beta in the fetal, neonatal, and prepubertal human prostate. The Prostate. 2002;52(1):69–81
  8. Aumuller G, Holterhus PM, Konrad L, et al. Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate. Anatomy and Embryology. 1998;197(3):199–208
  9. Takeda H, Lasnitzki I, Mizuno T. Analysis of prostatic bud induction by brief androgen treatment in the fetal rat urogenital sinus. The Journal of Endocrinology. 1986;110(3):467–470
  10. Takeda H, Mizuno T, Lasnitzki I. Autoradiographic studies of androgen-binding sites in the rat urogenital sinus and postnatal prostate. The Journal of Endocrinology. 1985;104(1):87–92
  11. Sajjad Y, Quenby S, Nickson P, et al. Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos. Reproduction (Cambridge, England). 2004;128(3):331–339
  12. Yamada G, Satoh Y, Baskin LS, et al. Cellular and molecular mechanisms of development of the external genitalia. Differentiation; Research in Biological Diversity. 2003;71(8):445–460
  13. Nef S, Parada LF. Hormones in male sexual development. Genes & Development. 2000;14(24):3075–3086
  14. Nef S, Parada LF. Cryptorchidism in mice mutant for Insl3. Nature Genetics. 1999;22(3):295–299
  15. Ahmed SF, Cheng A, Dovey L, et al. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. The Journal of Clinical Endocrinology and Metabolism. 2000;85(2):658–665
  16. Hughes IA, Acerini CL. Factors controlling testis descent. European Journal of Endocrinology. 2008;159(Suppl. 1):S75–S82
  17. Hutson JM. Testicular feminization: a model for testicular descent in mice and men. Journal of Pediatric Surgery. 1986;21(3):195–198
  18. Heyns CF, Pape VC. Presence of a low capacity androgen receptor in the gubernaculum of the pig fetus. The Journal of Urology. 1991;145(1):161–167
  19. Heyns CF, Tate R, Sargent NS, et al. Absence of 5 alpha-reductase activity in the gubernaculum during descent of the fetal pig testis. The Journal of Urology. 1993;150(2 Pt 1):510–513
  20. Ng SL, Bidarkar SS, Sourial M, et al. Gubernacular cell division in different rodent models of cryptorchidism supports indirect androgenic action via the genitofemoral nerve. Journal of Pediatric Surgery. 2005;40(2):434–441
  21. Yong EX, Huynh J, Farmer P, et al. Calcitonin gene-related peptide stimulates mitosis in the tip of the rat gubernaculum in vitro and provides the chemotactic signals to control gubernacular migration during testicular descent. Journal of Pediatric Surgery. 2008;43(8):1533–1539
  22. Miyagawa S, Satoh Y, Haraguchi R, et al. Genetic interactions of the androgen and Wnt/{beta}-catenin pathways for the masculinization of external genitalia. Molecular Endocrinology. 2009;23(6):871–880
  23. Holterhus PM, Sinnecker GH, Hiort O. Phenotypic diversity and testosterone-induced normalization of mutant L712F androgen receptor function in a kindred with androgen insensitivity. The Journal of Clinical Endocrinology and Metabolism. 2000;85(9):3245–3250
  24. Papadimitriou DT, Linglart A, Morel Y, et al. Puberty in subjects with complete androgen insensitivity syndrome. Hormone Research. 2006;65(3):126–131
  25. Steltenkamp S, Hiort O. Pubertal development of 46, XY DSD patients with partial androgen insensitivity due to mutation of the androgen receptor assigned to male sex. Hormone Research. 2007;68(Suppl. 1):205
  26. Hiort O, Holterhus PM, Horter T, et al. Significance of mutations in the androgen receptor gene in males with idiopathic infertility. The Journal of Clinical Endocrinology and Metabolism. 2000;85(8):2810–2815
  27. Galli-Tsinopoulou A, Hiort O, Schuster T, et al. A novel point mutation in the hormone binding domain of the androgen receptor associated with partial and minimal androgen insensitivity syndrome. Journal of Pediatric Endocrinology & Metabolism. 2003;16(2):149–154
  28. Bouvattier C, Carel JC, Lecointre C, et al. Postnatal changes of T, LH, and FSH in 46, XY infants with mutations in the AR gene. The Journal of Clinical Endocrinology and Metabolism. 2002;87(1):29–32
  29. Boukari K, Meduri G, Brailly-Tabard S, et al. Lack of androgen receptor expression in Sertoli cells accounts for the absence of anti-Mullerian hormone repression during early human testis development. The Journal of Clinical Endocrinology and Metabolism. 2009;94(5):1818–1825
  30. Rey RA, Belville C, Nihoul-Fekete C, et al. Evaluation of gonadal function in 107 intersex patients by means of serum antimullerian hormone measurement. The Journal of Clinical Endocrinology and Metabolism. 1999;84(2):627–631
  31. Kubini K, Zachmann M, Albers N, et al. Basal inhibin B and the testosterone response to human chorionic gonadotropin correlate in prepubertal boys. The Journal of Clinical Endocrinology and Metabolism. 2000;85(1):134–138
  32. Aiman J, Griffin JE, Gazak JM, et al. Androgen insensitivity as a cause of infertility in otherwise normal men. The New England Journal of Medicine. 1979;300(5):223–227
  33. Sinnecker GH, Hiort O, Nitsche EM, et al. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. European Journal of Pediatrics. 1997;156(1):7–14
  34. Holterhus PM, Wiebel J, Sinnecker GH, et al. Clinical and molecular spectrum of somatic mosaicism in androgen insensitivity syndrome. Pediatric Research. 1999;46(6):684–690
  35. Deeb A, Mason C, Lee YS, et al. Correlation between genotype, phenotype and sex of rearing in 111 patients with partial androgen insensitivity syndrome. Clinical Endocrinology. 2005;63(1):56–62
  36. Holterhus PM, Werner R, Hoppe U, et al. Molecular features and clinical phenotypes in androgen insensitivity syndrome in the absence and presence of androgen receptor gene mutations. Journal of Molecular Medicine. 2005;
  37. Coutant R, Mallet D, Lahlou N, et al. Heterozygous mutation of steroidogenic factor-1 in 46, XY subjects may mimic partial androgen insensitivity syndrome. The Journal of Clinical Endocrinology and Metabolism. 2007;92(8):2868–2873
  38. Lee YS, Kirk JM, Stanhope RG, et al. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clinical Endocrinology. 2007;67(1):20–28
  39. Hiort O, Willenbring H, Albers N, et al. Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency. European Journal of Pediatrics. 1996;155(6):445–451
  40. La Spada AR, Wilson EM, Lubahn DB, et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 1991;352(6330):77–79
  41. Lavery DN, McEwan IJ. The human androgen receptor AF1 transactivation domain: interactions with transcription factor IIF and molten-globule-like structural characteristics. Biochemical Society Transactions. 2006;34(Pt 6):1054–1057
  42. Matias PM, Donner P, Coelho R, et al. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. The Journal of Biological Chemistry. 2000;275(34):26164–26171
  43. Shaffer PL, Jivan A, Dollins DE, et al. Structural basis of androgen receptor binding to selective androgen response elements. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(14):4758–4763
  44. He B, Gampe RT, Kole AJ, et al. Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance. Molecular Cell. 2004;16(3):425–438
  45. Verrijdt G, Tanner T, Moehren U, et al. The androgen receptor DNA-binding domain determines androgen selectivity of transcriptional response. Biochemical Society Transactions. 2006;34(Pt 6):1089–1094
  46. Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: structure and function. Current Opinion in Cell Biology. 1998;10(3):384–391
  47. Smith DF, Toft DO. Minireview: the intersection of steroid receptors with molecular chaperones: observations and questions. Molecular Endocrinology. 2008;22(10):2229–2240
  48. Schaufele F, Carbonell X, Guerbadot M, et al. The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(28):9802–9807
  49. Jenster G, Trapman J, Brinkmann AO. Nuclear import of the human androgen receptor. The Biochemical Journal. 1993;293(Pt 3):761–768
  50. Claessens F, Denayer S, Van Tilborgh N, et al. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nuclear Receptor Signaling. 2008;6:e008
  51. Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocrine Reviews. 2007;28(7):778–808
  52. Link KA, Burd CJ, Williams E, et al. BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF. Molecular and Cellular Biology. 2005;25(6):2200–2215
  53. Chen J, Kinyamu HK, Archer TK. Changes in attitude, changes in latitude: nuclear receptors remodeling chromatin to regulate transcription. Molecular Endocrinology. 2006;20(1):1–13
  54. Chen D, Ma H, Hong H, et al. Regulation of transcription by a protein methyltransferase. Science. 1999;284(5423):2174–2177
  55. Kang Z, Janne OA, Palvimo JJ. Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. Molecular Endocrinology. 2004;
  56. Gehin M, Mark M, Dennefeld C, et al. The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Molecular and Cellular Biology. 2002;22(16):5923–5937
  57. Yong W, Yang Z, Periyasamy S, et al. Essential role for Co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology. The Journal of Biological Chemistry. 2007;282(7):5026–5036
  58. Hong J, Kim ST, Tranguch S, et al. Deficiency of co-chaperone immunophilin FKBP52 compromises sperm fertilizing capacity. Reproduction (Cambridge, England). 2007;133(2):395–403
  59. Beleza-Meireles A, Barbaro M, Wedell A, et al. Studies of a co-chaperone of the androgen receptor, FKBP52, as candidate for hypospadias. Reproductive Biology and Endocrinology. 2007;5:8
  60. Gottlieb B, Beitel LK, Wu JH, et al. The androgen receptor gene mutations database (ARDB): 2004 update. Human Mutation. 2004;23(6):527–533
  61. Tahiri B, Auzou G, Nicolas JC, et al. Participation of critical residues from the extreme C-terminal end of the human androgen receptor in the ligand binding function. Biochemistry. 2001;40(29):8431–8437
  62. Werner R, Zhan J, Gesing J, et al. In-vitro characterization of androgen receptor mutations associated with complete androgen insensitivity syndrome reveals distinct functional deficits. Sexual Development. 2008;2(2):73–83
  63. Holterhus PM, Werner R, Struve D, et al. Mutations in the amino-terminal domain of the human androgen receptor may be associated with partial androgen insensitivity and impaired transactivation in vitro. Experimental and Clinical Endocrinology & Diabetes. 2005;113(8):457–463
  64. Ferlin A, Vinanzi C, Garolla A, et al. Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clinical Endocrinology. 2006;65(5):606–610
  65. Jeske YW, McGown IN, Cowley DM, et al. Androgen receptor genotyping in a large Australasian cohort with androgen insensitivity syndrome; identification of four novel mutations. Journal of Pediatric Endocrinology & Metabolism. 2007;20(8):893–908
  66. Ledig S, Jakubiczka S, Neulen J, et al. Novel and recurrent mutations in patients with androgen insensitivity syndromes. Hormone Research. 2005;63(6):263–269
  67. Avila DM, Wilson CM, Nandi N, et al. Immunoreactive AR and genetic alterations in subjects with androgen resistance and undetectable AR levels in genital skin fibroblast ligand-binding assays. The Journal of Clinical Endocrinology and Metabolism. 2002;87(1):182–188
  68. Beitel LK, Prior L, Vasiliou DM, et al. Complete androgen insensitivity due to mutations in the probable alpha-helical segments of the DNA-binding domain in the human androgen receptor. Human Molecular Genetics. 1994;3(1):21–27
  69. Ris-Stalpers C, Turberg A, Verleun-Mooyman MC, et al. Expression of an aberrantly spliced androgen receptor mRNA in a family with complete androgen insensitivity. Annals of the New York Academy of Sciences. 1993;684:239–242
  70. Hellwinkel OJ, Holterhus PM, Struve D, et al. A unique exonic splicing mutation in the human androgen receptor gene indicates a physiologic relevance of regular androgen receptor transcript variants. The Journal of Clinical Endocrinology and Metabolism. 2001;86(6):2569–2575
  71. Holterhus PM, Bruggenwirth HT, Hiort O, et al. Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome. The Journal of Clinical Endocrinology and Metabolism. 1997;82(11):3584–3589
  72. Hiort O, Sinnecker GH, Holterhus PM, et al. Inherited and de novo androgen receptor gene mutations: investigation of single-case families. The Journal of Pediatrics. 1998;132(6):939–943
  73. Kohler B, Lumbroso S, Leger J, et al. Androgen insensitivity syndrome: somatic mosaicism of the androgen receptor in seven families and consequences for sex assignment and genetic counseling. The Journal of Clinical Endocrinology and Metabolism. 2005;90(1):106–111
  74. Holterhus PM, Sinnecker GH, Wollmann HA, et al. Expression of two functionally different androgen receptors in a patient with androgen insensitivity. European Journal of Pediatrics. 1999;158(9):702–706
  75. Mhatre AN, Trifiro MA, Kaufman M, et al. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nature Genetics. 1993;5(2):184–188
  76. Werner R, Holterhus PM, Binder G, et al. 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. The Journal of Clinical Endocrinology and Metabolism. 2006;91(9):3515–3520
  77. Lundin KB, Giwercman A, Richthoff J, et al. No association between mutations in the human androgen receptor GGN repeat and inter-sex conditions. Molecular Human Reproduction. 2003;9(7):375–379
  78. Lundin KB, Nordenskjold A, Giwercman A, et al. Frequent finding of the androgen receptor A645D variant in normal population. The Journal of Clinical Endocrinology and Metabolism. 2006;91(8):3228–3231
  79. Tut TG, Ghadessy FJ, Trifiro MA, et al. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. The Journal of Clinical Endocrinology and Metabolism. 1997;82(11):3777–3782
  80. Davis-Dao CA, Tuazon ED, Sokol RZ, et al. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. The Journal of Clinical Endocrinology and Metabolism. 2007;92(11):4319–4326
  81. Milatiner D, Halle D, Huerta M, et al. Associations between androgen receptor CAG repeat length and sperm morphology. Human Reproduction (Oxford, England). 2004;19(6):1426–1430
  82. Lim HN, Chen H, McBride S, et al. Longer polyglutamine tracts in the androgen receptor are associated with moderate to severe undermasculinized genitalia in XY males. Human Molecular Genetics. 2000;9(5):829–834
  83. Dowsing AT, Yong EL, Clark M, et al. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene. Lancet. 1999;354(9179):640–643
  84. Lund A, Tapanainen JS, Lahdetie J, et al. Long CAG repeats in the AR gene are not associated with infertility in Finnish males. Acta obstetricia et gynecologica Scandinavica. 2003;82(2):162–166
  85. Hadjkacem L, Hadj-Kacem H, Boulila A, et al. Androgen receptor gene CAG repeats length in fertile and infertile Tunisian men. Annales de génétique. 2004;47(3):217–224
  86. Lavery R, Houghton JA, Nolan A, et al. CAG repeat length in an infertile male population of Irish origin. Genetica. 2005;123(3):295–302
  87. Lubahn DB, Brown TR, Simental JA, et al. 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. Proceedings of the National Academy of Sciences of the United States of America. 1989;86(23):9534–9538
  88. Holterhus PM, Deppe U, Werner R, et al. 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
  89. Appari M, Werner R, Wunsch L, et al. Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome. Journal of Molecular Medicine. 2009;87:623–632
  90. Cato AC, Henderson D, Ponta H. The hormone response element of the mouse mammary tumour virus DNA mediates the progestin and androgen induction of transcription in the proviral long terminal repeat region. The EMBO Journal. 1987;6(2):363–368
  91. Govindan MV. Specific region in hormone binding domain is essential for hormone binding and trans-activation by human androgen receptor. Molecular Endocrinology. 1990;4(3):417–427
  92. Thompson J, Saatcioglu F, Janne OA, et al. Disrupted amino- and carboxyl-terminal interactions of the androgen receptor are linked to androgen insensitivity. Molecular Endocrinology. 2001;15(6):923–935
  93. Zuccarello D, Ferlin A, Vinanzi C, et al. Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. Clinical Endocrinology. 2007;
  94. Werner R, Schutt J, Hannema S, et al. Androgen receptor gene mutations in androgen insensitivity syndrome cause distinct patterns of reduced activation of androgen-responsive promoter constructs. The Journal of Steroid Biochemistry and Molecular Biology. 2006;101(1):1–10
  95. Bebermeier JH, Brooks JD, Deprimo SE, et al. Cell-line and tissue-specific signatures of androgen receptor-coregulator transcription. Journal of Molecular Medicine. 2006;84(11):919–931
  96. Dubbink HJ, Hersmus R, Verma CS, et al. Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor. Molecular Endocrinology. 2004;18(9):2132–2150
  97. He B, Kemppainen JA, Wilson EM. FXXLF and WXXLF sequences mediate the NH2-terminal interaction with the ligand binding domain of the androgen receptor. The Journal of Biological Chemistry. 2000;275(30):22986–22994
  98. He B, Gampe RT, Hnat AT, et al. Probing the functional link between androgen receptor coactivator and ligand-binding sites in prostate cancer and androgen insensitivity. The Journal of Biological Chemistry. 2006;281(10):6648–6663
  99. He B, Kemppainen JA, Voegel JJ, et al. Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH(2)-terminal domain. The Journal of Biological Chemistry. 1999;274(52):37219–37225
  100. Ghali SA, Gottlieb B, Lumbroso R, et al. The use of androgen receptor amino/carboxyl-terminal interaction assays to investigate androgen receptor gene mutations in subjects with varying degrees of androgen insensitivity. The Journal of Clinical Endocrinology and Metabolism. 2003;88(5):2185–2193
  101. Wong HY, Hoogerbrugge JW, Pang KL, et al. A novel mutation F826L in the human androgen receptor in partial androgen insensitivity syndrome; increased NH2-/COOH-terminal domain interaction and TIF2 co-activation. Molecular and Cellular Endocrinology. 2008;292(1-2):69–78
  102. Nguyen D, Steinberg SV, Rouault E, et al. A G577R mutation in the human AR P box results in selective decreases in DNA binding and in partial androgen insensitivity syndrome. Molecular Endocrinology. 2001;15(10):1790–1802
  103. Bruggenwirth HT, Boehmer AL, Lobaccaro JM, et al. Substitution of Ala564 in the first zinc cluster of the deoxyribonucleic acid (DNA)-binding domain of the androgen receptor by Asp, Asn, or Leu exerts differential effects on DNA binding. Endocrinology. 1998;139(1):103–110
  104. Farla P, Hersmus R, Geverts B, et al. The androgen receptor ligand-binding domain stabilizes DNA binding in living cells. Journal of Structural Biology. 2004;147(1):50–61
  105. van Royen ME, Cunha SM, Brink MC, et al. Compartmentalization of androgen receptor protein-protein interactions in living cells. The Journal of Cell Biology. 2007;177(1):63–72
  106. Jaaskelainen J, Deeb A, Schwabe JW, et al. Human androgen receptor gene ligand-binding-domain mutations leading to disrupted interaction between the N- and C-terminal domains. Journal of Molecular Endocrinology. 2006;36(2):361–368
  107. Bevan CL, Brown BB, Davies HR, et al. Functional analysis of six androgen receptor mutations identified in patients with partial androgen insensitivity syndrome. Human Molecular Genetics. 1996;5(2):265–273
  108. Wang Q, Ghadessy FJ, Trounson A, et al. Azoospermia associated with a mutation in the ligand-binding domain of an androgen receptor displaying normal ligand binding, but defective trans-activation. The Journal of Clinical Endocrinology and Metabolism. 1998;83(12):4303–4309
  109. Quigley CA, Tan JA, He B, et al. Partial androgen insensitivity with phenotypic variation caused by androgen receptor mutations that disrupt activation function 2 and the NH(2)- and carboxyl-terminal interaction. Mechanisms of Ageing and Development. 2004;125(10-11):683–695
  110. Hughes IA, Houk C, Ahmed SF, et al. Consensus statement on management of intersex disorders. Archives of Disease in Childhood. 2006;91(7):554–563
  111. Weidemann W, Peters B, Romalo G, et al. Response to androgen treatment in a patient with partial androgen insensitivity and a mutation in the deoxyribonucleic acid-binding domain of the androgen receptor. The Journal of Clinical Endocrinology and Metabolism. 1998;83(4):1173–1176

PII: S1521-690X(09)00143-2

doi: 10.1016/j.beem.2009.11.002

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 24, Issue 2 , Pages 263-277 , April 2010

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