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Androgen Receptors in Normal and Abnormal Male Sexual Differentiation

  • Terry R. Brown
  • Claude J. Migeon
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 196)

Abstract

Androgens act in target tissues via specific intracellular receptors. Indeed, all the functions controlled by androgen effects are mediated by androgen receptors, including sexual differentiation during fetal life, maturation at puberty and maintenance of sexual function and fertility in adult life. In this review, we will describe: A) the physiology of male sexual differentiation; B) abnormalities of male sexual differentiation; and C) studies of androgen receptors in man and their relationship to the pathophysiology of abnormal androgen action.

Keywords

Androgen Receptor Leydig Cell External Genitalia Human Skin Fibroblast Gonadal Dysgenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    A. Jost, Problems of fetal endocrinology: the gonadal and hypophyseal hormones. Recent Prog. Horm. Res. 8: 379 (1953).Google Scholar
  2. 2.
    A. Jost, B. Vigier, J. Prepin and J. P. Perchellet, Studies on sex differentiation in mammals. Recent Prog. Horm. Res. 29: 1 (1973).PubMedGoogle Scholar
  3. 3.
    R. Schwartz, W. Brooks and H. H. Zinsser, Evidence of chemotaxis as a factor in sperm motility. Fertil Steril 9: 300 (1958).PubMedGoogle Scholar
  4. 4.
    E. Witschi, Migrations of germ cells of human embryos from the yolk sac to the primitive gonadal folds. Contrib. Embryol. 32: 67 (1948).Google Scholar
  5. 5.
    J. Jirasek, Development of the Genital System and Male Pseudohermaphroditism. Johns Hopkins Press, Baltimore (1971).Google Scholar
  6. 6.
    G. L. Stretter, Developmental horizons in human embryos. Age groups XI to XXIII. Contrib Embryol Carnegie Inst, Washington, D.C.Google Scholar
  7. 7.
    E. J. Eichwald and C. R. Silmser, Transplant Bull 2: 148 (1955).PubMedGoogle Scholar
  8. 8.
    E. H. Goldberg, E. A. Boyse, D. Bennett, M. Scheid and E. A. Carswell, Serological demonstration of H-Y (male) antigen on mouse sperm. Nature (London) 232: 478 (1971).Google Scholar
  9. 9.
    S. S. Wachtel, S. Ohno, G. C. Koo, E. A. Boyse, Possible role for H-Y antigen in the primary determination of sex. Nature 257: 235 (1975).PubMedCrossRefGoogle Scholar
  10. 10.
    S. Ohno, Major regulatory genes for mammalian sexual develop-ment. Cell 7: 315 (1976).PubMedCrossRefGoogle Scholar
  11. 11.
    S. Ohno, Y. Nagai, S. Ciccarese and H. Iwata, Testis organizing H-Y antigen and the primary sex determining mechanism of mammals. Recent Prog. Horm. Res. 35: 449 (1979).PubMedGoogle Scholar
  12. 12.
    S. S. Wachtel, Conservatism of the H-Y/H-W receptor. Hum. Genet. 58: 54 (1981).PubMedGoogle Scholar
  13. 13.
    S. S. Wachtel and G. C. Koo, H-Y antigen in gonad differentiation. In: Mechanisms of Sex Differentiation in Animals and Man. CR Austin and RG Edwards (eds) Academic Press, New York, p. 255 (1981).Google Scholar
  14. 14.
    W. K. Silvers, D. L. Gasser and E. M. Eicher, H-Y antigen, serologically detectable male antigen, and sex determination. Cell 28: 439 (1982).PubMedCrossRefGoogle Scholar
  15. 15.
    U. Wolf, M. Fraccaro, A. Mayerova, T. Hecht, 0. Zuffardi and H. Hameister. Turner patients are H-Y positive. Human Genet. 54: 315 (1980).CrossRefGoogle Scholar
  16. 16.
    W. Engel, B. Klemme and A. Ebrecht, Serological evidence for H-Y antigen in XO-female mice. Human Genet 57: 68 (1981).CrossRefGoogle Scholar
  17. 17.
    F. Celada and W. J. Welshons, An immunogenetic analysis of the male antigen in mice utilizing animals with an exceptional chromosome constitution. Genetics 48: 139 (1963).PubMedGoogle Scholar
  18. 18.
    E. M. Eicher, L. L. Washburn, J. B. Whitney III and K. E. Morrow, Mus Psochiavinus Y chromosome in the C57BL/6J murine genome causes sex reversal. Science 217: 535 (1982).PubMedCrossRefGoogle Scholar
  19. 19.
    E. M. Eicher, Primary sex determining genes in mice. In Prospects for Sexing Mammalian Sperm. RP Amann and EG Siedel, Jr. (eds) Colorado Associated University Press, Boulder, p 121 (1982).Google Scholar
  20. 20.
    J. Simpson, Gonadal dysgenesis and sex chromosome abnormalities, phenotype-karyotypic correlations. In Genetic Mechanisms of Sexual Development. LH Vallet and IH Porter (eds) Academic Press, New York. (1979).Google Scholar
  21. 21.
    C. G. Heller and Y. Clermont, Kinetics of the germinal epithelium in man. Rec. Prog. Horm. Res. 20: 545 (1964).PubMedGoogle Scholar
  22. 22.
    P. Gruenwald, The development of the sex cords in the gonads of man and mammals. Am. J. Anat. 70: 359 (1942).CrossRefGoogle Scholar
  23. 23.
    J. Wilson, Sexual differentiation. Ann. Rev. Physiol. 40: 279 (1978).CrossRefGoogle Scholar
  24. 24.
    R. Mancini, R. Narbaitz and J. LaVieri, Origin and development of the germinal epithelium and sertoli cells in the human testis: Cytological, cytochemical, and quantitative study. Anat. Rec. 136: 477 (1960).PubMedCrossRefGoogle Scholar
  25. 25.
    N. Josso, J. Y. Picard and D. Tran, The anti-mullerian hormone. Recent Prog Horm. Res. 33: 117 (1977).Google Scholar
  26. 26.
    M. G. Blanchard and N. Josso, Source of the anti-mullerian hormone synthesized by the fetal testis: mullerian-inhibiting activity of fetal bovine Sertoli cells in tissue culture. Pediat. Res. 8: 968 (1974).PubMedCrossRefGoogle Scholar
  27. 27.
    F. I. Reyes, J. S. D. Winter and C. Faiman, Studies on human sexual development. I. Fetal gonadal and adrenal sex steroids. J. Clin. Endocrinol. Metab. 37: 74 (1973).PubMedCrossRefGoogle Scholar
  28. 28.
    D. R. Abramovich and P. Rowe, Fetal plasma testosterone levels at mid-pregnancy and at term: relationship to fetal sex. J. Endocrinol. 56: 621 (1973).PubMedCrossRefGoogle Scholar
  29. 29.
    R. C. Diez d’Aux and B. E. P. Murphy, Androgens in the human fetus. J. Steroid Biochem. 5: 207 (1974).PubMedCrossRefGoogle Scholar
  30. 30.
    M. G. Forest, P. C. Sizonenko, A. M. Cathiard and J. Bertrand, Hypophyso-gonadal function in infants during the first year of life. I. Evidence for testicular activity in early infancy. J. Clin. Invest. 53: 819 (1974).PubMedCrossRefGoogle Scholar
  31. 31.
    M. G. Forest and A. M. Cathiard, Pattern of plasma testosterone and A4-androstenedione in normal newborns: evidence for testicular activity at birth. J. Clin. Endocrinol. Metab. 41: 977 (1975).PubMedCrossRefGoogle Scholar
  32. 32.
    B. R. Rice, C. A. Johanson and W. H. Sternberg, Formation of steroid hormones from acetate-1–14C by a human fetal testis preparation grown in organ culture. Steroids 7: 79 (1966).PubMedCrossRefGoogle Scholar
  33. 33.
    R. B. Jaffe, P. A. Lee and A. R. Midgley, Jr., Serum gonadotropins before, at the inception of, and following human pregnancy. J. Clin. Endocrinol. Metab. 29: 1281 (1969).PubMedCrossRefGoogle Scholar
  34. 34.
    J. L. Vaitukaitis, Changing placental concentrations of hCG and its subunits during gestation. J. Clin. Endocrinol Metab. 38: 744 (1974).CrossRefGoogle Scholar
  35. 35.
    C. Hagen and A. S. McNeilly, The gonadotropins and their subunits in fetal pituitary glands and circulation. J. Steroid Biochem. 8: 437 (1977).CrossRefGoogle Scholar
  36. 36.
    S. L. Kaplan, M. M. Grumbach and M. L. Aubert, The ontogenesis of pituitary hormones and hypothalamic factors in the human fetus: maturation of the central nervous system, regulation of the anterior pituitary function. Recent Prog. Horm. Res. 32: 161 (1976).PubMedGoogle Scholar
  37. 37.
    T. M. Siler-Khodr and G. S. Khodr, Studies in human fetal endocrinology. I. Luteinizing hormone releasing factor content of the hypothalamus. Am. J. Obstet Gynecol. 130: 795 (1978).PubMedGoogle Scholar
  38. 38.
    K. R. Fichman, B. R. Migeon and C. J. Migeon, Genetic Disorders of Male Sexual Differentiation. In Advances in Human Genetics. Plenum Press, New York; 10:333 (1980).Google Scholar
  39. 39.
    W. H. Pearlman, O. Crepy and M. Murphy, Testosterone-binding levels in the serum of women during the normal menstrual cycle, pregnancy and the post-partum period. J. Clin. Endocrinol. Metab. 27: 1012 (1967).PubMedCrossRefGoogle Scholar
  40. 40.
    M. G. Forest, M. A. Rivarola and C. J. Migeon, Percentage binding of testosterone, androstenedione and dehydroisoandrosterone in human plasma. Steroids 12: 323 (1968).PubMedCrossRefGoogle Scholar
  41. 41.
    L. Chan and B. W. O’Malley, Mechanism of action of sex steroid hormones. N. Engl. J. Med. 294: 1322 (1976).PubMedCrossRefGoogle Scholar
  42. 42.
    S. Liao, Molecular actions of androgens. In Biochemical Actions of Hormones. Litwack, G., (ed): Academic Press, New York (1977).Google Scholar
  43. 43.
    N. Bruchovsky and J. Wilson, The conversion of testosterone to 501-androstan-178-o1–3-one by rat prostate in vivo and in vitro. J. Biol. Chem. 213: 2012 (1968).Google Scholar
  44. 44.
    P. K. Siiteri and J. D. Wilson, Testosterone formation and metabolism during male sexual differentiation in the human embryo. J. Clin. Endocrinol. Metab. 38: 113 (1974).PubMedCrossRefGoogle Scholar
  45. 45.
    R. J. Moore, J. E. Griffin and J. D. Wilson, Diminished 5areductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, Type 2. J. Biol. Chem. 250: 7168 (1975).PubMedGoogle Scholar
  46. 46.
    J. Imperato-McGinley and R. Peterson, Male pseudohermaphroditism: The complexities of the male phenotypic development. Am. J. Med. 61: 251 (1976).PubMedCrossRefGoogle Scholar
  47. 47.
    C. J. Migeon, Male Pseudohermaphroditism. Annales d’Endocrinologie (Paris) 41: 311 (1980).Google Scholar
  48. 48.
    G. Koo, S. Wachtel, K. Krupen-Brown, L. Mittl, W. Breg, M. Genel, I. Rosenthal, D. Borgoankar, D. Miller, R. Tantravahi, R. Schreck, B. Erlanger, 0. Miller, Mapping the locus of the H-Y gene on the human Y chromosome. Science 198: 940 (1977).PubMedCrossRefGoogle Scholar
  49. 49.
    R. Franks, K. Bunting, E. Engel, Male pseudohermaphroditism with XYY sex chromosomes. J. Clin. Endocrinol. Metab. 27: 1623 (1967).PubMedCrossRefGoogle Scholar
  50. 50.
    A. Baghdassarian, F. Bayard, D. Borgaonkar, E. Arnold, K. Solex, C. Migeon, Testicular function in XYY men. Johns Hopkins Med. J. 136: 15 (1975).PubMedGoogle Scholar
  51. 51.
    N. Shakkebaek, J. Phillip, M. Mikkelsen, R. Hammen, J. Nielsen, O. Perboll, H. Yde, Studies on spermatogenesis, meiotic chromosomes and sperm morphology in two males with 47 XYY chromosome complement. Fertil. Steril. 21: 645 (1970).Google Scholar
  52. 52.
    J. Leonard, C. Paulsen, L. Ospina, E. Burgess, The classification of Klinefelter’s syndrome. In: Genetic Mechanisms of Sexual Development. LH Vallet and IH Porter (eds) Academic Press, New York. (1979).Google Scholar
  53. 53.
    M. Grumbach, J. Van Wyk, Disorders of sexual differentiation. In: Textbook of Endocrinology. R Williams (ed), W. B. Saunders Co., Philadelphia, (1974).Google Scholar
  54. 54.
    E. Niebuhr, Triploidy in man. Humangenetik 21: 103 (1974).PubMedCrossRefGoogle Scholar
  55. 55.
    A. De La Chapelle, Nature and origin of males with XX chromosomes. Am. J. Hum. Genet. 24: 71 (1972).PubMedGoogle Scholar
  56. 56.
    H. Ferguson-Smith, X-Y chromosomal interchange in the etiology of true hermaphroditism and of XX Klinefelter’s syndrome. Lancet ii: 475 (1966).Google Scholar
  57. 57.
    H. Rosenberg, G. Clayton, T. Hsu, Familial true hermaphroditism. J. Clin. Endocrinol. Metab. 23: 203 (1963).PubMedCrossRefGoogle Scholar
  58. 58.
    G. D. Berkovitz, J. A. Rock, M. D. Urban and C. J. Migeon, True hermaphroditism. Johns Hopkins Med. J. 151: 290 (1982).PubMedGoogle Scholar
  59. 59.
    M. Cohen, M. Shaw, Two XY siblings with gonadal dysgenesis and a female phenotype. N. Engl. J. Med. 272: 1083 (1965).PubMedCrossRefGoogle Scholar
  60. 60.
    S. Armendares, L. Buentello, S. Frenk, Two male sibs with uterus and fallopian tubes, a rare, probably inherited disorder. Clin. Genetics 4: 291 (1973).CrossRefGoogle Scholar
  61. 61.
    F. Berthezene, M. Forest, J. Grimaud, B. Clasutrat, R. Mornex, Leydig cell agenesis: A cause of male pseudohermaphroditism. N. Engl. J. Med. 295: 969 (1976).PubMedCrossRefGoogle Scholar
  62. 62.
    J. Park, L. Burnett, H. Jones, C. Migeon, R. Blizzard, A case of male pseudohermaphroditism associated with elevated LH, normal FSH and low testosterone possibly due to the secretion of an abnormal LH molecule. Acta. Endocrinol. 83: 173 (1976).PubMedGoogle Scholar
  63. 63.
    G. Perez-Palacios, H. Scaglia, S. Kofman, D. Saavedra, S. Ochoa, 0. Laroza, A. Perez, Inherited deficiency of gonadotropin receptor in Leydig cells: A new form of male pseudohermaphroditism. Am. J. Hum. Genet. 27: 71A (1975).Google Scholar
  64. 64.
    W. Meyer, B. Keena, L. deLacerda, I. Park, H. Jones, C. Migeon, Familial male pseudohermaphroditism with normal Leydig cell function at puberty. J. Clin. Endocrinol. Metab. 46: 593 (1978).PubMedCrossRefGoogle Scholar
  65. 65.
    P. Siiteri, J. Wilson, Testosterone formation and metabolism during male sexual differentiation in the human embryo. J. Clin. Endocrinol. Metab. 38: 113 (1974).PubMedCrossRefGoogle Scholar
  66. 66.
    B. S. Keenan, W. J. Meyer, A. J. Hadjian, H. W. Jones, C. J. Migeon, Syndrome of androgen insensitivity in man: absence of 5a-dihydrotestosterone binding protein in skin fibroblasts. J. Clin. Endocrinol. Metab. 38: 1143 (1974).PubMedCrossRefGoogle Scholar
  67. 67.
    T. R. Brown, C. J. Migeon, Cultured human skin fibroblasts: a model for the study of androgen action. Molec. Cell. Biochem. 36: 3 (1981).PubMedCrossRefGoogle Scholar
  68. 68.
    K. R. Fichman, L. M. Nyberg, P. Bujnovszky, T. R. Brown, P. C. Walsh, The ontogeny of the androgen receptor in human foreskin. J. Clin. Endocrinol. Metab. 52: 919 (1981).PubMedCrossRefGoogle Scholar
  69. 69.
    C. Sultan, B. R. Migeon, S. W. Rothwell, M. Maes, N. Zerhouni, C. J. Migeon, Androgen receptors and metabolism in cultured human fetal fibroblasts. Pediatr. Res. 14: 67 (1980).PubMedGoogle Scholar
  70. 70.
    B. W. Keenan, W. J. Meyer, A. J. Hadjian, C. J. Migeon, Androgen receptor in human skin fibroblasts: characterization of a specific 5cr androstan-l718-ol-3-one protein complex in cell sonicates and nuclei. Steroids 25: 535 (1975).PubMedCrossRefGoogle Scholar
  71. 71.
    M. Maes, C. Sultan, N. Zerhouni, S. W. Rothwell, C. J. Migeon, Role of testosterone binding to the androgen receptor in male sexual differentiation of patients with 5a-reductase deficiency. J. Steroid Biochem. 11: 1385 (1979).PubMedCrossRefGoogle Scholar
  72. 72.
    G. D. Berkovitz, T. R. Brown, C. J. Migeon, Inhibition of 5areductase activity and alteration of nuclear testosterone: dihydrotestosterone ratio in human genital skin fibroblats. J. Andrology 5: 171 (1984).Google Scholar
  73. 73.
    T. R. Brown, S. W. Rothwell, C. J. Migeon, Comparison of methyltrienolone and dihydrotestosterone binding and metabolism in human genital skin fibroblasts. J. Steroid Biochem. 14: 1013 (1981).PubMedCrossRefGoogle Scholar
  74. 74.
    T. R. Brown, S. W. Rothwell, C. Sultan, C. J. Migeon, Inhibition of androgen binding in human foreskin fibroblasts by anti-androgens. Steroids 37: 635 (1981).PubMedCrossRefGoogle Scholar
  75. 75.
    T. R. Brown, S. W. Rothwell, C. J. Migeon, Human androgen insensitivity mutation does not alter oligonucleotide recognition by the androgen receptor-DHT complex. Molec. Cell. Endocrinol. 32: 215 (1983).PubMedCrossRefGoogle Scholar
  76. 76.
    T. R. Brown, C. J. Migeon, Androgen binding in nuclear matrix of human genital skin fibroblasts, 7th International Congress of Endocrinology International Congress Series No 652 Excerpta Medica, Amsterdam p510 abstract (1984).Google Scholar
  77. 77.
    D. M. Pardoll, B. Vogelstein, D. S. Coffey, A fixed site of DNA replication in eukaryotic cells. Cell 19: 527 (1980).PubMedCrossRefGoogle Scholar
  78. 78.
    S. I. Robinson, B. D. Nelkin, B. Vogelstein, The ovalbumin gene is associated with the nuclear matrix of chicken oviduct cells. Cell 28: 99 (1982).PubMedCrossRefGoogle Scholar
  79. 79.
    C. W. Bardin, L. P. Bullock, R. J. Sherins, I. Mowszowicz, W. R. Blackburn, Androgen metabolism and mechanism of action in male pseudohermaphroditism: a study of testicular feminization. Rec. Prog. Horm. Res. 29: 65 (1973).PubMedGoogle Scholar
  80. 80.
    J. E. Griffin, K. Punyashthiti, J. D. Wilson, Dihydrotestosterone binding by cultured human fibroblasts: comparison of cells from control subjects and from patients with hereditary male pseudohermaphrotidism due to androgen resistance. J. Clin. Invest. 57: 1342 (1976).PubMedCrossRefGoogle Scholar
  81. 81.
    M. Kaufman, C. Straisfeld, L. Pinsky, Male pseudohermaphroditism presumably due to target organ unresponsiveness to androgens. J. Clin. Invest. 58: 345 (1976).PubMedCrossRefGoogle Scholar
  82. 82.
    T. T. Puck, A. Robins, T. H. Tijo, Familial primary amenorrhea due to testicular feminization: a human gene affecting sex differentiation. Proc. Soc. Exptl. Biol. Med. 103: 192 (1960).Google Scholar
  83. 83.
    M. F. Lyon, S. G. Hawkes, X-linked gene for testicular feminization in the mouse. Nature 227: 1217 (1970).PubMedCrossRefGoogle Scholar
  84. 84.
    S. Ohno, M. F. Lyon, X-linked testicular feminization in the mouse as a non-inducible regulatory mutation of the Jacob-Monod type. Clin. Genet. 1: 121 (1970).CrossRefGoogle Scholar
  85. 85.
    W. J. Meyer, B. R. Migeon, C. J. Migeon, Locus on human X-chromosome for dihydrotestosterone receptor and androgen insensitivity. Proc. Natl. Acad. Sci. USA 72: 1469 (1975).PubMedCrossRefGoogle Scholar
  86. 86.
    B. R. Migeon, T. R. Brown, J. Axelman, C. J. Migeon, Studies of the locus for androgen receptor: localization on the human X-chromosome and evidence for homology with the Tfm locus in the mouse. Proc. Natl. Acad. Sci. USA 78: 6339Google Scholar
  87. 87.
    J. A. Amrhein, W. S. Meyer, H. W. Jones, C. J. Migeon, Androgen insensitivity in man: evidence for genetic heterogeneity. Proc. Natl. Acad. Sci. USA 73: 891 (1976).PubMedCrossRefGoogle Scholar
  88. 88.
    J. W. Pike, S. Dokoh, M. R. Haussier, U. A. Liberman, S. J. Marx, C. Eil, Vitamin D3-resistant fibroblasts have immunoassayable 1,25-dihydroxyvitamin D3 receptors. Science 224: 870 (1984).CrossRefGoogle Scholar
  89. 89.
    T. R. Brown, M. Maes, S. W. Rothwell, C. J. Migeon, Human complete androgen insensitivity with normal dihydrotestosterone receptor binding capacity in cultured genital skin fibroblasts: evidence for a qualitative abnormality of the receptor. J. Clin. Endocrinol. Metab. 55: 61 (1982).PubMedCrossRefGoogle Scholar
  90. 90.
    M. K. El-Awady, D. R. Allman, J. E. Griffin, J. D. Wilson, Expression of a mutant androgen receptor in cloned fibroblasts derived from a heterozygous carrier for the syndrome of testicular feminization. Am. J. Hum. Genet. 35: 376 (1983).Google Scholar
  91. 91.
    J. A. Amrhein, G. Jones-Klingensmith, P. C. Walsh, V. A. McKusick, C. J. Migeon, Partial androgen insensitivity: the Reifenstein syndrome revisited. N. Engl. J. Med. 297: 350 (1977).PubMedCrossRefGoogle Scholar
  92. 92.
    J. E. Griffin, Testicular feminization associated with a thermolabile androgen receptor in cultured human fibroblasts. J. Clin. Invest. 64: 1624 (1979).PubMedCrossRefGoogle Scholar
  93. 93.
    M. Kaufman, L. Pinsky, L. Simard, S. C. Wong, Defective activation of androgen-receptor complexes. A marker of androgen insensitivity. Molec Cell Endocrinol 25: 151 (1982).PubMedCrossRefGoogle Scholar
  94. 94.
    J. Aiman, J. E. Griffin, J. M. Gazak, J. D. Wilson, P. C. MacDonald, Androgen insensitivity as a cause of infertility in otherwise normal men. N. Engl. J. Med. 300: 223 (1979).PubMedCrossRefGoogle Scholar
  95. 95.
    J. Aiman, J. E. Griffin, The frequency of androgen receptor deficiency in infertile men. J. Clin. Endocrinol. Metab. 54: 725 (1982).PubMedCrossRefGoogle Scholar
  96. 96.
    C. J. Migeon, T. R. Brown, R. Lanes, A. Palacios, J. A. Amrhein, E. J. Schoen, A clinical syndrome of mild androgen insensitivity. J. Clin. Endocrinol. Metab. 59: 672 (1984).PubMedCrossRefGoogle Scholar
  97. 97.
    J. Imperato-McGinley, R. Peterson, M. Leshin, J. E. Griffin, G. Cooper, S. Draghi, M. Berenyi, J. D. Wilson, Steroid 5a -reductase deficiency in a 65-year old male pseudohermaphrodite: the natural history, ultrastructure of the testes, and evidence for inherited enzyme heterogeneity. J. Clin. Endocrinol. Metab. 50: 15 (1980).PubMedCrossRefGoogle Scholar
  98. 98.
    A. Ferenczy, R. M. Richart, The fine structure of the gonads in the complete form of testicular feminization syndrome. Am. J. Obstet. Gynec. 113: 399 (1972).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Terry R. Brown
    • 1
  • Claude J. Migeon
    • 1
  1. 1.Department of Pediatrics, Pediatric Endocrine Clinic and LaboratoriesThe Johns Hopkins University, School of MedicineBaltimoreUSA

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