Androgens and the Androgen Receptor in Male Sex Development and Fertility

  • Loretta L. Collins
  • Chang Chawnshang 


The androgen receptor (AR) is a member of the nuclear receptor superfamily and acts as a transcription factor to modulate expression of target genes ((Chang et al., 1988a; Chang et al., 1988b; Lubahn et al., 1988a; Lubahn et al., 1988b; Tilley et al., 1989; Trapman et al., 1988). As a classical steroid hormone receptor, AR requires the binding of a ligand for activation of its function as a transcriptional modulator. The classical ligands known to activate AR include testosterone (T) and its metabolites, such as 5α-dihydrotestosterone (DHT). Once a ligand is bound, AR undergoes a change in conformation and phosphorylation status, allowing the receptor to bind to target gene DNA response elements. Recruitment of specific coregulators alters the regulatory effect AR has on target gene expression (see Chapter 4 of this volume by Heinlein et al.). However, it has been proposed that androgens act independently of AR to produce non-genomic effects (Rommerts, 1998) (see Chapter 5 of this volume by Heinlein and Chang), and that AR may function without binding to DNA (Slagsvold et al., 2001). AR is expressed nearly ubiquitously in mammalian tissues (Kimura et al., 1993; Sar et al., 1990; Tilley et al., 1990), and is known to play various biological roles in areas including development, sexual and reproductive function, immune function, and homeostasis (Quigley, 1998).


Androgen Receptor Sertoli Cell Androgen Receptor Gene Sperm Maturation Wolffian Duct 
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  1. Abou-Haila, A., Orgebin-Crist, M.C., Skudlarek, M.D. and Tulsiani, D.R.P. Identification and androgen regulation of egasyn in the mouse epididymis. Biochimica et Biophysica Acta 1998; 1401: 177–186PubMedGoogle Scholar
  2. Adham, I.M., Emmen, J.M.A. and Engel, W. The role of the testicular factor INSL3 in establishing the gonadal position. Molecular and Cellular Endocrinology 2000; 160: 11–16PubMedGoogle Scholar
  3. Allard, S., Adin, P., Gouedard, L., di Clemente, N., Josso, N., Orgebin-Crist, M.C., Picard, J.Y. and Xavier, F. Molecular mechanisms of hormone-mediated Mullerian duct regression: involvement of beta-catenin. Development 2000; 127: 3349–3360PubMedGoogle Scholar
  4. Anderson, R.A., Wallace, E.M., Groome, N.P., Bellis, A.J. and Wu, F.C.W. Physiological relationships between inhibin B, follicle stimulating hormone secretion and spermatogenesis in normal men and response to gonadotrophin suppression by exogenous testosterone. Human Reproduction 1997; 12: 746–751PubMedGoogle Scholar
  5. Avila, D.M., Zoppi, S. and McPhaul, M.J. The androgen receptor (AR) in syndromes of androgen insensitivity and in prostate cancer. Journal of Steroid Biochemistry & Molecular Biology 2001; 76: 135–142Google Scholar
  6. Baarends, W.M., van Helmond, M.J.L., Post, M., van der Schoot, P.J.C.M., Hoogerbrugge, J.W., de Winter, J.P., Uilenbroek, J.T.J., Karels, B., Wilming, L.G., Meijers, J.H.C., Themmen, A.P.N, and Grootegoed, J.A. A novel member of the transmembrane serine/threonine kinase receptor family is specifically expressed in the gonads and in mesenchymal cells adjacent to the Mullerian duct. Development 1994; 120: 189–197PubMedGoogle Scholar
  7. Barbieri, M.A., Sosa, M.A., Couso, R., Ielpi, L., Merello, S., Tonn, C.E. and Bertini, F. Affinity sites for N-acetyl-D-glucosaminidase on the surface of rat epididymal spermatozoa. International Journal of Andrology 1994; 17: 43–49PubMedGoogle Scholar
  8. Barthold, J.S., Kumasi-Rivers, K., Upadhyay, J., Shekarriz, B. and Imperato-McGinley, J. Testicular position in the androgen insensitivity syndrome: Implications for the role of androgens in testicular descent. The Journal of Urology 2000; 164Google Scholar
  9. Barthold, J.S., Mahler, H.R. and Newton, B.W. Lack of feminization of the cremaster nucleus in cryptorchid androgen insensitive rats. Journal of Urology 1994; 152: 2280–2286PubMedGoogle Scholar
  10. Bashir, M.S. and Wells, M. Mullerian inhibiting substance. Journal of Pathology 1995; 176: 109–110PubMedGoogle Scholar
  11. Beasley, S.W. and Hutson, J.M. The role of the gubernaculum in testicular descent. Journal of Urology 1988; 140: 1191–1193PubMedGoogle Scholar
  12. Belmonte, S.A., Challa, A., Gutierrez, L.S., Bertini, F. and Sosa, M.A. alpha-Mannosidase from rat epididymal fluid is a ligand for phosphomannosyl receptors on the sperm surface. International Journal of Andrology 1998; 21: 277–282PubMedGoogle Scholar
  13. Bercu, B.B., Jackson, I.M.D., Sawin, C.T., Safaii, H. and Reichlin, S. Permanent impairment of testicular development after transient immunological blockade of endogenous luteinizing releasing hormone in the neonatal rat. Endocrinology 1977; 101: 1871–1879PubMedGoogle Scholar
  14. Bidlingmaier, F., Dorr, H.G., Eisenmenger, W., Kuhnle, U. and Knorr, D. Testosterone and androstendione concentrations in human testis and epididymis during the first two years of life. Journal of Clinical Endocrinology and Metabolism 1983; 57: 311–315PubMedGoogle Scholar
  15. Blaquier, J.A., Cameo, M.S. and Burgos, M.H. The role of androgens in the maturation of epididymal spermatozoa in the guinea pig. Endocrinology 1972; 90: 839–842PubMedGoogle Scholar
  16. Blaquier, J.A., Cameo, M.S., Cuasnicu, P.S., Echeverria, M.F.G., Pineiro, L., Tezon, J.G. and Vazquez, M.H. On the role of epididymal factors in sperm fertility. Reproduction, Nutrition, Developpement 1988; 28: 1209–1216Google Scholar
  17. Bongso, A. and Trounson, A. Evaluation of motility, fertilizing ability and embryonic development of murine epididymal sperm after co-culture with epididymal epithelium. Human Reproduction 1996; 11: 1451–1456PubMedGoogle Scholar
  18. Bremner, W.J., Millar, M.R., Sharpe, R.M. and Saunders, P.T.K. Immunohistochemical localization of androgen receptors in the rat testis: Evidence for stage-dependent expression and regulation by androgens. Endocrinology 1994; 135: 1227–1234PubMedGoogle Scholar
  19. Brinkmann, A.O. Molecular basis of androgen insensitivity. Molecular and Cellular Endocrinology 2001; 179: 105–109PubMedGoogle Scholar
  20. Brinkmann, A.O., Jenster, G., Ris-Stalpers, C, van der Korput, J.A.G.M., Bruggenwirth, H.T., Boehmer, A.L.M. and Trapman, J. Androgen receptor mutations. Journal of Steroid Biochemistry & Molecular Biology 1995; 53: 443–448Google Scholar
  21. Brooks, D.E. and Higgins, S.J. Characterization and androgen-dependence of proteins associated with luminal fluid and spermatozoa in the rat epididymis. Journal of Reproduction and Fertility 1980; 59: 363–375PubMedGoogle Scholar
  22. Brown, D.V., Amann, R.P. and Wagley, L.M. Influence of rete testis fluid on the metabolism of testosterone by cultured principal cells isolated from the proximal or distal caput of the rat epididymis. Biology of Reproduction 1983; 28: 1257–1268PubMedGoogle Scholar
  23. Cain, M.P., Kramer, S.A., Tindall, D.J. and Husmann, D.A. Flutamide-induced cryptorchidism in the rat is associated with altered gubernacular morphology. Urology 1995;46:553–558PubMedGoogle Scholar
  24. Cameo, M.S. and Blaquier, J.A. Androgen-controlled specific proteins in rat epididymis. Journal of Endocrinology 1976; 69Google Scholar
  25. Cameron, D.F. and Muffly, K.E. Hormonal regulation of spermatid binding. Journal of Cell Science 1991; 100:623–633PubMedGoogle Scholar
  26. Cameron, D.F., Muffly, K.E. and Nazian, S.J. Reduced testosterone during puberty results in a midspermiogenic lesion. Proceedings of the Society for Experimental Biology and Medicine 1993; 202: 457–464PubMedGoogle Scholar
  27. Carballada, R. and Saling, P.M. Regulation of mouse epididymal epithelium in vitro by androgens, temperature and fibroblasts. Journal of Reproduction and Fertility 1997; 110: 171–181PubMedGoogle Scholar
  28. Castellon, E.A. and Huidobro, C.C. Androgen regulation of glycosidase secretion in epithelial cell cultures from human epididymis. Human Reproduction 1999; 14: 1522–1527PubMedGoogle Scholar
  29. Cattanach, B.M., Iddon, C.A., Charlton, H.M., Chiappa, S.A. and Fink, G. Gonadotropin-releasing hormone deficiency in a mutant mouse with hypogonadism. Nature 1977; 269: 338–340PubMedGoogle Scholar
  30. Chang, C., Kokontis, J. and Liao, S. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 1988a; 240: 324–326Google Scholar
  31. Chang, C., Kokontis, J. and Liao, S. Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors. Proceedings of the National Academy of Sciences 1988b; 85: 7211–7215Google Scholar
  32. Charlton, H.M., Halpin, D.M.G., Iddon, C., Rosie, R., Levy, G., McDowell, I.F.W., Megson, A., Morris, J.F., Bramwell, A., Speight, A., Ward, B.J., Broadhead, J., Davey- Smith, G. and Fink, G. The effects of daily administration of single and multiple injections of gonadotropin-releasing hormone on pituitary and gonadal function in the hypogonadal (hpg) mouse. Endocrinology 1983; 113: 535–544PubMedGoogle Scholar
  33. Chemes, H.E. (1996) Leydig cell development in humans. In Payne, A.H., Hardy, M.P. and Russell, L.D. (eds.), The Leydig Cell. Cache River Press, Vienna, IL, pp. 176–202.Google Scholar
  34. Cheuk, B.L.Y., Leung, P.S., Lo, A.C.T. and Wong, P.Y.D. Androgen control of cyclooxygenase expression in the rat epididymis. Biology of Reproduction 2000; 63: 775–780PubMedGoogle Scholar
  35. Cooke, P.S., Young, P. and Cunha, G.R. Androgen receptor expression in developing male reproductive organs. Endocrinology 1991; 128: 2867–2873PubMedGoogle Scholar
  36. Cooper, T.G., Yeung, C.H., Nashan, D. and Nieschlag, E. Epididymal markers in human infertility. Journal of Andrology 1988; 9: 91–101PubMedGoogle Scholar
  37. Cuthbert, A.W. and Wong, P.Y. Electrogenic anion secretion in cultured rat epididymal epithelium. Journal of Physiology 1986; 378: 335–345PubMedGoogle Scholar
  38. Dierich, A., Sairam, MR., Monaco, L., Fimia, G.M., Gansmuller, A., LeMeur, M. and Sassone-Corsi, P. Imparing follicle-stimulating hormone (FSH) signaling in vivo: Targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proceedings of the National Academy of Sciences 1998; 95: 13612–13617Google Scholar
  39. Dowsing, A.T., Yong, E.L., Clark, M., McLachlan, R.I., de Kretser, D.M. and Trounson, A.O. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene. Lancet 1999; 354: 640–643PubMedGoogle Scholar
  40. Dyson, A.L.M.B. and Orgebin-Crist, M.C. Effect of hypophosectomy, castration and androgen replacement upon the fertilizing ability of rat epididymal spermatozoa. Endocrinology 1973; 93: 391–402PubMedGoogle Scholar
  41. Emmen, J.M.A., McLuskey, A., Adham, I.M., Engel, W., Grootegoed, J.A. and Brinkmann, A.O. Hormonal control of gubernaculum development during testis descent: Gubernaculum outgrowth in vitro requires both insulin-like factor and androgen. Endocrinology 2000; 141: 4720–4727PubMedGoogle Scholar
  42. Emmen, J.M.A., McLuskey, A., Grootogoed, J.A. and Brinkman, A.O. Androgen action during male sex differentiation includes suppression of cranial suspensory ligament development. Human Reproduction 1998; 13: 1272–1280PubMedGoogle Scholar
  43. England, M.A. (1983) A colour atlas of life before birth: Normal fetal development. Wolfe Medical, Netherlands.Google Scholar
  44. Frohlich, O., Po, C., Murphy, T. and Young, L.G. Multiple promoter and splicing mRNA variants of the epididymis-specific gene EP2. Journal of Andrology 2000; 21: 421–430PubMedGoogle Scholar
  45. George, F.W., Catt, K.J., Neaves, W.B. and Wilson, J.D. Studies on the regulation of testosterone synthesis in the fetal rabbit testis. Endocrinology 1978; 102: 665–673PubMedGoogle Scholar
  46. George, F.W. and Peterson, K.G. Partial characterization of the androgen receptor of the newborn rat gubernaculum. Biology of Reproduction 1988; 39: 536–539PubMedGoogle Scholar
  47. Ghadessy, F.J., Lim, J., Abdullah, A.A.R., Panet-Raymond, V., Choo, C.K., Lumbroso, R., Tut, T.G., Gottlieb, B., Pinsky, L., Trifiro, M.A. and Yong, E.L. Oligospermic infertility associated with an androgen receptor mutation that disrupts interdomain and coactivator (TIF2) interactions. Journal of Clinical Investigation 1999; 103: 1517–1525PubMedGoogle Scholar
  48. Giwercman, Y.L., Nikoshkov, A., Lindsten, K., Bystrom, B., Pousette, A., Knudtzon, J., Aim, J. and Wedell, A. Response to treatment in patients with partial androgen insensitivity due to mutations in the DNA-binding domain of the androgen receptor. Hormone Research 2000; 53: 83–88Google Scholar
  49. Goh, D.W., Middlesworth, W., Farmer, P.J. and Hutson, J.M. Prenatal androgen blockade with flutamide inhibits masculinization of the genitofemoral nerve and testicular descent. Journal of Pediatric Surgery 1994; 29: 836–838PubMedGoogle Scholar
  50. Grocock, C.A., Charlton, H.M. and Pike, M.C. Role of the fetal pituitary in cryptorchidism induced by exogenous maternal oestrogen during pregnancy in mice. Journal of Reproduction and Fertility 1988; 83: 295–300PubMedGoogle Scholar
  51. Haendler, B., Habenicht, U.F., Schwidetzky, U., Schuttke, I. and Schleuning, W.D. Differential androgen regulation of the murine genes for cysteine-rich secretory proteins (CRISP). European Journal of Biochemistry 1997; 250: 440–446PubMedGoogle Scholar
  52. Hamil, K.G., Sivashanmugam, P., Richardson, R.T., Grossman, G., Ruben, S.M., Mohler, J.L., Petrusz, P., O’Rand, M.G., French, F.S. and Hall, S.H. HE2beta and HE2gamma, new members of an epididymis-specific family of androgen-regulated proteins in the human. Endocrinology 2000; 141: 1245–1253PubMedGoogle Scholar
  53. Handelsman, D.J., Spaliviero, J.A., Simpson, J.M., Allan, C.A. and Singh, J. Spermatogenesis without gonadotropins: Maintenance has a lower testosterone threshold than initiation. Endocrinology 1999; 140: 3938–3946PubMedGoogle Scholar
  54. Harris, G.C., Frayne, J. and Nicholson, H.D. Epididymal oxytocin in the rat: its origin and regulation. International Journal of Andrology 1996; 19: 278–286PubMedGoogle Scholar
  55. Heyns, C.F. The gubernaculum during testicular descent in the human fetus. Journal of Anatomy 1987; 153: 93–112PubMedGoogle Scholar
  56. Heyns, C.F., Human, H.J., Werely, C.J. and de Klerk, D.P. The glycosaminoglycans of the gubernaculum during testicular descent in the fetus. Journal of Urology 1990; 143: 612–617PubMedGoogle Scholar
  57. Heyns, C.F. and Hutson, J.M. Historical review of theories on testicular descent. Journal of Urology 1995; 153: 754–767PubMedGoogle Scholar
  58. Heyns, C.F. and Pape, V.C. Presence of a low capacity androgen receptor in the gubernaculum of the pig fetus. Journal of Urology 1991; 145: 161–167PubMedGoogle Scholar
  59. Hiort, O., Holterhus, P., Horter, T., Schulze, W., Kremke, B., Bals-Pratsch, M., Sinnecker, G.H.G. and Kruse, K. Significance of mutations in the androgen receptor gene in males with idiopathic infertility. Journal of Clinical Endocrinology and Metabolism 2000; 85: 2810–2815PubMedGoogle Scholar
  60. Hrabovszky, Z., Farmer, P.J. and Hutson, J.M. Does the sensory nucleus of the genitofemoral nerve have a role in testicular descent? Journal of Pediatric Surgery 2000; 36: 96–100Google Scholar
  61. Hrabovszky, Z., Farmer, P.J. and Hutson, J.M. Undescended testis is accompanied by calcitonin gene-related peptide accumulation within the sensory nucleus of the genitofemoral nerve in trans-scrotal rats. The Journal of Urology 2001; 165: 1015–1018PubMedGoogle Scholar
  62. Hughes, I.A. Minireview: Sex differentiation. Endocrinology 2001; 142: 3281–3287PubMedGoogle Scholar
  63. Husmann, D.A. and Levy, J.B. Current concepts in the pathophisiology of testicular undescent. Urology 1995; 46: 267–274PubMedGoogle Scholar
  64. Husmann, D.A. and McPhaul, M.J. Time-specific androgen blockade with flutamide inhibits testicular descent in the rat. Endocrinology 1991; 129: 1409–1416PubMedGoogle Scholar
  65. Husmann, D.A. and McPhaul, M.J. Reversal of flutamide-induced cryptorchidism by prenatal time-specific androgens. Endocrinology 1992; 131: 1711–1715PubMedGoogle Scholar
  66. Hutson, J.M. Testicular feminization: A model for testicular descent in mice and men. Journal of Pediatric Surgery 1986; 21: 195–198PubMedGoogle Scholar
  67. Hutson, J.M. Normal testicular descent and the aetiology of cryptorchidism. Advances in Anatomy, Embryology & Cell Biology 1996; 132: 1–56Google Scholar
  68. Hutson, J.M., Hasthorpe, S. and Heyns, C.F. Anatomical and functional aspects of testicular descent and cryptorchidism. Endocrine Reviews 1997; 18: 259–280PubMedGoogle Scholar
  69. Ibrahim, N.M., Young, L.G. and Frohlich, O. Epididymal specificity and androgen regulation of rat EP2. Biology of Reproduction 2001; 65: 575–580PubMedGoogle Scholar
  70. Jervis, K.M. and Robaire, B. Dynamic changes in gene expression along the rat epididymis. Biology of Reproduction 2001; 65: 696–703PubMedGoogle Scholar
  71. Josso, N., di Clemente, N. and Gouedard, L. Anti-Mullerian hormone and its receptors. Molecular and Cellular Endocrinology 2001; 179: 25–32PubMedGoogle Scholar
  72. Jost, A. Problems of fetal endocrinology: The gonadal and hypophyseal hormones. Recent Progress in Hormone Research 1953; 8: 379–418Google Scholar
  73. Ketelslegers, J.M., Hetzel, W.D., Sherins, R.J. and Catt, K.J. Developmental changes in testicular gonadotropin receptors: Plasma gonadotropins and plasma testosterone in the rat. Endocrinology 1978; 103: 212–222PubMedGoogle Scholar
  74. Kimura, N., Mizokami, A., Oonuma, T., Sasano, H. and Nagura, H. Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. The Journal of Histochemistry and Cytochemistry 1993; 41: 671–678PubMedGoogle Scholar
  75. Kubota, Y., Nef, S., Farmer, P.J., Temelcos, C, Parada, L.F. and Hutson, J.M. Leydig insulinlike hormone, gubernacular development and testicular descent. The Journal of Urology 2001; 165: 1673–1675PubMedGoogle Scholar
  76. Kumar, T.R., Wang, Y., Lu, N. and Matzuk, M.M. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nature Genetics 1997; 15: 201–204PubMedGoogle Scholar
  77. Lai, K.B., Fu, W.O., Ko, W.H., Chan, H.C. and Wong, P.Y. The effect of [Arg8]vasopressin on eletrogenic chloride secretion in cultured rat epididymal epithelia. American Journal of Physiology 1994; 267: C607–C616PubMedGoogle Scholar
  78. Larkins, S.L., Williams, M.P.L. and Hutson, J.M. Localization of calcitonin gene-related peptide within the spinal nucleus of the genitofemoral nerve. Pediatric Surgery International 1991; 6: 176–179Google Scholar
  79. Lee, M.M. and Donahoe, P.K. Mullerian inhibiting substance: A gonadal hormone with multiple functions. Endocrine Reviews 1993; 14: 152–164PubMedGoogle Scholar
  80. Lee, V.W.K., de Kretser, D.M., Hudson, B. and Wang, C. Variations in serum FSH, LH, and testosterone levels in male rats from birth to sexual maturity. Journal of Reproduction and Fertility 1975; 42: 121–126PubMedGoogle Scholar
  81. Lei, Z.M., Mishra, S., Zou, W., Xu, B., Foltz, M., Li, X. and Rao, C.V. Targeted disruption of luteinizing hormone / human chorionic gonadotropin receptor gene. Molecular Endocrinology 2001; 15: 184–200PubMedGoogle Scholar
  82. Lim, H.N., Nixon, R.M., Chen, H., Hughes, LA. and Hawkins, J.R. Evidence that longer androgen receptor ployglutamine repeats are a causal factor for genital abnormalities. The Journal of Clinical Endocrinology and Metabolism 2001; 86: 3207–3210PubMedGoogle Scholar
  83. Lindsey, J.S. and Wilkinson, M.F. An androgen-regulated homeobox gene expressed in rat testis and epididymis. Biology of Reproduction 1996a; 55: 975–983Google Scholar
  84. Lindsey, J.S. and Wilkinson, M.F. Pern: A testosterone- and LH-regulated homeobox gene expressed in mouse Sertoli cells and epididymis. Developmental Biology 1996b; 179:471–484Google Scholar
  85. Liu, H., Sun, G., Shy, S. and Shyu, H. Postnatal development and testosterone-dependence of GP-83 and GP-49, two sperm maturation-related glycoproteins in BALB/c mouse epididymis. Cell Tissue Research 1992; 269: 189–194PubMedGoogle Scholar
  86. Lubahn, D.B., Joseph, D.R., Sar, M., Tan, J., Higgs, H.N., Larson, R.E., French, F.S. and Wilson, E.M. The human androgen receptor: Complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate. Molecular Endocrinology 1988a; 2: 1265–1275Google Scholar
  87. Lubahn, D.B., Joseph, D.R., Sullivan, P.M., Willard, H.F., French, F.S. and Wilson, E.M. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988b; 240: 327–330Google Scholar
  88. Luo, X., Ikeda, Y. and Parker, K.L. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 1994; 77: 481–490PubMedGoogle Scholar
  89. Lyon, M.F., Glenister, P.H. and Lamoreux, M.L. Normal spermatozoa from androgen-resistant germ cells of chimaeric mice and the role of androgen in spermatogenesis. Nature 1975; 258: 620–622PubMedGoogle Scholar
  90. Mason, A.J., Hayflick, J.S., Zoeller, R.T., Young III, W.S., Phillips, H.S., Nikolics, K. and Seeburg, P.H. A deletion truncating in the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science 1986; 234: 1366–1371PubMedGoogle Scholar
  91. Mather, J.P., Moore, A. and Li, R. Activins, inhibins, and follistatins: Further thoughts on a growing family of regulators. Proceedings of the Society for Experimental Biology and Medicine 1997; 215: 209–222PubMedGoogle Scholar
  92. Mathieu, C, Lejeune, H., Guerin, J., Pinatel, M., Cognat, M. and Lornage, J. Motility and fertilizing capacity of epididymal human spermatozoa in normal and pathological cases. Fertility and Sterility 1992; 57: 871–876PubMedGoogle Scholar
  93. Mayorga, L.S. and Bertini, F. Effect of androgens on the activity of acid hydrolases in rat epididymis. International Journal of Andrology 1982; 5: 345–352PubMedGoogle Scholar
  94. Mayorga, L.S. and Bertini, F. The origin of some acid hydrolases of the fluid of the rat cauda epididymis. Journal of Andrology 1985; 6: 243–245PubMedGoogle Scholar
  95. McPhaul, M.J. Molecular defects of the androgen receptor. Journal of Steroid Biochemistry & Molecular Biology 1999; 69: 315–322Google Scholar
  96. Mifsud, A., Sim, C.K.S., 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. Fertility and Sterility 2001; 75: 275–281Google Scholar
  97. Moore, H.D.M. and Hartman, T.D. In-vitro development of the fertilizing ability of hamster epididymal spermatozoa after co-culture with epithelium from the proximal cauda epididymis. Journal of Reproduction and Fertility 1986; 78: 347–352PubMedGoogle Scholar
  98. Moore, H.D.M., Hartman, T.D. and Smith, C.A. In-vitro culture of hamster epididymal epithelium and induction of sperm motility. Journal of Reproduction and Fertility 1986;78:327–336PubMedGoogle Scholar
  99. Morohashi, K., Hatano, O., Noumra, M., Takayama, K., Hara, M., Yoshii, H., Takakusu, A. and Omura, T. Function and distribution of a steroidogenic cell-specific transcription factor, Ad4BP. Journal of Steroid Biochemistry & Molecular Biology 1995; 53: 81–88Google Scholar
  100. O’Donnell, L., McLachlan, R.I., Wreford, N.G. and Robertson, D.M. Testosterone promotes the conversion of round spermatids between Stages VII and VIII of the rat spermatogenic cycle. Endocrinology 1994; 135: 2608–2614PubMedGoogle Scholar
  101. Orgebin-Crist, M.C. Sperm maturation in rabbit epididymis. Nature 1967; 216: 816–818PubMedGoogle Scholar
  102. Osterhoff, C, Kirchhoff, C, Krull, N. and Ivell, R. Molecular cloning and characterization of a novel human sperm antigen (HE2) specifically expressed in the proximal epididymis. Biology of Reproduction 1994; 50: 516–525PubMedGoogle Scholar
  103. Quigley, C.A. (1998) The androgen receptor: Physiology and pathophysiology. In Nieschlag, E. and Behre, H.M. (eds.), Testosterone: action, deficiency, substitution. Springer-Verlag, Heidelberg, pp. 33–106.Google Scholar
  104. Racine, C, Rey, R., Forest, M.G., Louis, F., Ferre, A., Huhtaniemi, I., Josso, N. and di Clemente, N. Receptors for anti-Mullerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proceedings of the National Academy of Sciences 1998; 95: 594–599Google Scholar
  105. Raczek, S., Yeung, C.H., Hasilik, A., Robenek, H., Hertile, L., Schulze, H. and Cooper, T.G. Immunocytochemical localization of some lysosomal hydrolases, their presence in luminal fluid and their directional secretion by human epididymal cells in culture. Cell & Tissue Research 1995; 280: 415–425Google Scholar
  106. Regadera, J., Martinez-Garcia, F., Gonzalez-Peramato, P., Serrano, A., Nistal, M. and Suarez-Quian, C. Androgen receptor expression in Sertoli cells as a function of seminiferous tubule maturation in the human cryptorchid testis. The Journal of Clinical Endocrinology and Metabolism 2001; 86: 413–421PubMedGoogle Scholar
  107. Rey, R., Mebarki, F., Forest, M.G., Mowszowicz, I., Cate, R.L., Morel, Y., Chaussain, J.L. and Josso, N. Anti-Mullerian hormone in children with androgen insensitivity. The Journal of Clinical Endocrinology and Metabolism 1994; 79: 960–964PubMedGoogle Scholar
  108. Rommerts, F.F.G. (1998) Testosterone: An overview of biosynthesis, transport, metabolism and non-genomic actions. In Nieschlag, E. and Behre, H.M. (eds.), Testosterone: action, deficiency, substitution. Springer-Verlag, Heidelberg, pp. 1–31.Google Scholar
  109. Saez, J.M. Leydig cells: Endocrine, paracrine, and autocrine regulation. Endocrine Reviews 1994; 15: 574–626PubMedGoogle Scholar
  110. Sar, M., Lubahn, D.B., French, F.S. and Wilson, E.M. Immunohistochemical localization of the androgen receptor in rat and human tissues. Endocrinology 1990; 127: 3180–3186PubMedGoogle Scholar
  111. Sinclair, A.H. (1994) The cloning of SRY. In Wachtel, S.S. (ed.) Molecular genetics of sex determination. Academic Press, London, pp. 23–40.Google Scholar
  112. Sinclair, A.H., Berta, P., Palmer, M.S., Hawkins, J.R., Griffiths, B.L., Smith, M.J., Foster, J.W., Frischauf, A.M., Lovell-Badge, R. and Goodfellow, P.N. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 1990; 346: 240–244PubMedGoogle Scholar
  113. Singh, J. and Handelsman, D.J. The effects of recombinant FSH on testosterone-induced spermatogenesis in gonadotrophin-deficient (hpg) mice. Journal of Andrology 1996a; 17:382–393Google Scholar
  114. Singh, J. and Handelsman, D.J. Neonatal administration of FSH increases Sertoli cell numbers and spermatogenesis in gonadotropin-deficient (hpg) mice. Journal of Endocrinology 1996b; 151: 37–48Google Scholar
  115. Singh, J., O’Neill, C. and Handelsman, D.J. Induction of spermatogenesis by androgens in gonadotropin-deficient (hpg) mice. Endocrinology 1995; 136: 5311–5321PubMedGoogle Scholar
  116. Sivashanmugam, P., Richardson, R.T., Hall, S., Hamil, K.G., French, F.S. and O’Rand, M.G. Cloning and characterization of an androgen-dependent acidic epididymal glycoprotein/CRISPl-like protein from the monkey. Journal of Andrology 1999; 20: 384–393PubMedGoogle Scholar
  117. Skudlarek, M.D. and Orgebin-Crist, M.C. Glycosidases in cultured rat epididymal cells: enzyme activity, synthesis and secretion. Biology of Reproduction 1986; 35: 167–178PubMedGoogle Scholar
  118. Slagsvold, T., Kraus, I., Fronsdal, K. and Saatcioglu, F. DNA binding-independent transcriptional activation by the androgen receptor through triggering of coactivators. The Journal of Biological Chemistry 2001; 276: 31030–31036PubMedGoogle Scholar
  119. Soler, C., Yeung, C.H. and Cooper, T.G. Development of sperm motility patterns in the murine epididymis. International Journal of Andrology 1994; 17: 271–278PubMedGoogle Scholar
  120. Spencer, J.R., Torrado, T., Sanchez, R.S., E.D. Vaughan, J. and Imperato-McGinley, J. Effects of flutamide and finasteride on rat testicular descent. Endocrinology 1991; 129: 741–748PubMedGoogle Scholar
  121. Spencer, J.R., Vaughan Jr., E.D. and Imperato-McGinley, J. Studies of the hormonal control of postnatal testicular descent in the rat. Journal of Urology 1993; 149: 618–623PubMedGoogle Scholar
  122. Sultan, C., Migeon, B.R., Rothwell, S.W., Maes, M., Zerhouni, N. and Migeon, C.J. Androgen receptors and metabolism in cultured human fetal fibroblasts. Pediatric Research 1980; 14: 67–69PubMedGoogle Scholar
  123. Sun, Y., Wreford, N.G., Robertson, D.M. and de Kretser, D.M. Quantitative cytological studies of spermatogenesis in intact and hypophysectomized rats: Identification of androgen-dependent stages. Endocrinology 1990; 127: 1215–1223Google Scholar
  124. Suzuki, Y., Sasagawa, I., Tateno, T., Ashida, J., Nakada, T., Muroya, K. and Ogata, T. Mutation screening and CAG repeat length analysis of the androgen receptor gene in Kleinfelter’s syndrome patients with and without spermatogenesis. Human Reproduction 2001; 16: 1653–1656PubMedGoogle Scholar
  125. Teixeira, J., Fynn-Thompson, E., Payne, A. and Donahoe, P.K. Mullerian-inhibiting substance regulates androgen synthesis at the trascriptional level. Endocrinology 1999; 140:4732–4738PubMedGoogle Scholar
  126. Thompson, J., Saatcioglu, F., Janne, O.A. and Palvimo, J.J. Disrupted amino- and carboxyl-terminal interactions of the androgen receptor are linked to androgen insensitivity. Molecular Endocrinology 2001; 15: 923–935PubMedGoogle Scholar
  127. Tilley, W.D., Marcelli, M. and McPhaul, M.J. Expression of the human androgen receptor gene utilizes a common promoter in diverse human tissues and cell lines. The Journal of Biological Chemistry 1990; 265: 13776–13781PubMedGoogle Scholar
  128. Tilley, W.D., Marcelli, M., Wilson, J.D. and McPhaul, M.J. Characterization and expression of a cDNA encoding the human androgen receptor. Proceedings of the National Academy of Sciences 1989; 86: 327–331Google Scholar
  129. Tong, S.Y.C., Hutson, J.M. and Watts, L.M. Does testoterone diffuse down the Wolffian duct during sexual differentiation. Pediatric Urology 1996; 155: 2057–2059Google Scholar
  130. Trapman, J., Klaassen, P., Kuiper, G.G.J.M., van der Korput, J.A.G.M., Faber, P.W., van Rooij, H.C.J., van Kessel, A.G., Voorhorst, M.M., Mulder, E. and Brinkmann, A.O. Cloning, structure and expression of a cDNA encoding the human androgen receptor. Biochemical and Biophysical Research Communications 1988; 153: 241–248PubMedGoogle Scholar
  131. Tulsiani, D.R., NagDas, S.K., Skudlarek, M.D. and Orgebin-Crist, M.C. Rat sperm plasma membrane mannosidase: localization and evidence for proteolytic processing during epididymal maturation. Developmental Biology 1995a; 167: 584–595Google Scholar
  132. Tulsiani, D.R., Skudlarek, M.D., Araki, Y. and Orgebin-Crist, M.C. Purification and characterization of two forms of beta-D-galactosidase from rat epididymal luminal fluid: evidence for their role in the modification of sperm plasma membrane glycoproteins(s). Biochemical Journal 1995b; 305: 41–50Google Scholar
  133. Turner, T.T. Spermatozoa are exposed to a complex microenvironment as they traverse the epididymis. Annals of the New York Academy of Sciences 1991; 637: 364–383PubMedGoogle Scholar
  134. van der Schoot, P. Androgens in relation to prenatal development and postnatal inversion of the gubernacula in rats. Journal of Reproduction and Fertility 1992a; 95: 145–158Google Scholar
  135. van der Schoot, P. Disturbed testicular descent in the rat after prenatal exposure to the antiandrogen flutamide. Journal of Reproduction and Fertility 1992b; 96: 483–496Google Scholar
  136. van der Schoot, P. The name cranial ovarian suspensory ligaments in mammalian anatomy should be used only to indicate the structures derived from the foetal cranial mesonephric and gonadal ligaments. Anatomical Record 1993; 237: 434–438PubMedGoogle Scholar
  137. van der Schoot, P. and Elger, W. Perinatal development of gubernacular cones in rats and rabbits: Effect of exposure to anti-androgens. Anatomical Record 1993; 236: 399–407PubMedGoogle Scholar
  138. von Eckardstein, S., Syska, A., Gromoll, J., Kamischke, A., Simoni, M. and Nieschlag, E. Inverse correlation between sperm concentration and number of androgen receptors CAG repeats in normal men. Journal of Clinical Endocrinology and Metabolism 2001; 86: 2585–2590Google Scholar
  139. Vornberger, W., Prins, G., Musto, N.A. and Suarez-Quian, C.A. Androgen receptor distribution in rat testis: New implications for androgen regulation of spermatogenesis. Endocrinology 1994; 134: 2307–2316PubMedGoogle Scholar
  140. Wang, Q., Ghadessy, F.J., Trounson, A., de Kretser, D., McLachlan, R., Ng, S.C. and Yong, E.L. Azoospermia associated with a mutation in the ligand-binding domain of an androgen receptor displaying normal ligand binding, but defective trans activation. Journal of Clinical Endocrinology and Metabolism 1998; 83: 4303–4309PubMedGoogle Scholar
  141. Weinbauer, G.F. and Nieschlag, E. (1993) Hormonal control of spermatogenesis. In de Kretser, D. (ed.) Molecular Biology of the Male Reproductive System, pp. 101–142.Google Scholar
  142. Weinbauer, G.F. and Nieschlag, E. (1998) The role of testosterone in spermatogenesis. In Nieschlag, E. and Behre, H.M. (eds.), Testosterone: action, deficiency, substitution. Springer-Verlag, Heidelberg, pp. 143–168.Google Scholar
  143. Wilson, J.D., George, F.W. and Griffin, J.E. The hormonal control of sexual development. Science 1981; 211: 1278–1284PubMedGoogle Scholar
  144. Wong, P.Y., Fu, W.O. and Huang, S.J. Endothelin stimulates short current in a cultured epithelium. British Journal of Pharmacology 1989; 98: 1191–1196PubMedGoogle Scholar
  145. Wong, P.Y., Fu, W.O., Huang, S.J. and Law, W.K. Effect of angiotensins on electogenic anion transport in monolayer cultures of rat epididymis. Journal of Endocrinology 1990; 125: 449–456PubMedGoogle Scholar
  146. Young, L.G., Frohlich, O. and Gould, K.G. HE2/EP2, an androgen-dependent protein from the epididymis of the chimpanzee, Pan troglodytes. Journal of Reproduction and Fertility 1998; 53(suppl): 215–220PubMedGoogle Scholar
  147. Zhang, F.P., Poutanen, M., Wilbertz, J. and Huhtaniemi, I. Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Molecular Endocrinology 2001; 15: 172–183PubMedGoogle Scholar
  148. Zimmerman, S., Steding, G., Emmen, J.M.A., Brinkmann, A.O., Nayernia, K., Holstein, A.F., Engel, W. and Adham, I.M. Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Molecular Endocrinology 1999; 13: 681–691Google Scholar
  149. Zorgniotti, A.A. (ed.) (1991) Temperature and environmental effects on the testis. Plenum Press, New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Loretta L. Collins
    • 1
  • Chang Chawnshang 
    • 1
  1. 1.George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation OncologyUniversity of RochesterRochester

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