Androgen receptor roles in spermatogenesis and fertility: Lessons from testicular cell-specific androgen receptor knockout mice

Endocrine Reviews

Volumn 30, Issue 2, 2009, Pages 119-132

  Wang, Ruey Sheng ^a,b   Yeh, Shuyuan ^a   Tzeng, Chii Ruey ^b   Chang, Chawnshang ^a  

^a Medical Center   (United States)

^b School of Medicine   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; TESTOSTERONE;

ANDROGEN INSENSITIVITY SYNDROME; AUTOCRINE EFFECT; CELL FUNCTION; CELL MATURATION; CELL SPECIFICITY; EPIDIDYMIS; GENE DELETION; GENE EXPRESSION REGULATION; GERM CELL; HUMAN; LEYDIG CELL; MALE FERTILITY; MALE GENITAL SYSTEM; NONHUMAN; PARACRINE SIGNALING; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SERTOLI CELL; SMOOTH MUSCLE FIBER; SPERMATOCYTE; SPERMATOGENESIS; SPERMATOZOON COUNT; TESTICULAR FEMINIZATION; TESTIS CELL; TESTIS SIZE; TESTOSTERONE BLOOD LEVEL; TESTOSTERONE SYNTHESIS;

ANIMALS; FERTILITY; INFERTILITY, MALE; MALE; MICE; MICE, KNOCKOUT; MODELS, BIOLOGICAL; ORGAN SPECIFICITY; RECEPTORS, ANDROGEN; SPERMATOGENESIS; TESTIS; TESTOSTERONE;

EID: 65249154823     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2008-0025     Document Type: Review

References (138)

1. Chang JA, Nguyen HT, Lue TF 2002 Androgens in penile development, penile erection, and erectile dysfunction. In: Chang C, ed. Androgens and androgen receptor: mechanisms, functions and clinical applications. Norwell, MA: Kluwer Academic Publishers; 289-298
2. Collins LL, Chang C 2002 Androgens and the androgen receptor in male sex development and fertility. In: Chang C, ed. Androgens and androgen receptor: mechanisms, functions and clinical applications. Norwell, MA: Kluwer Academic Publishers; 299-323
3. Shumazaki S 2002 The role of 5-α reductase in prostate disease and male pattern baldness. In: Chang C, ed. Androgens and androgen receptor: mechanisms, functions and clinical applications. Norwell, MA: Kluwer Academic Publishers; 155-196
4. Quigley CA 1998 The androgen receptor: physiology and pathophysiology. In: Nieschlag E, Behre HM, eds. Testosterone: action, deficiency, substitution. Heidelberg: Springer-Verlag; 33-106
5. Chang CS, Kokontis J, Liao ST 1988 Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 240:324-326
6. Chang CS, Kokontis J, Liao ST 1988 Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors. Proc Natl Acad Sci USA 85:7211-7215
7. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM 1988 Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240: 327-330
8. Heinlein CA, Chang C 2002 Androgen receptor (AR) coregulators: an overview. Endocr Rev 23:175-200
9. Griffin JE 1992 Androgen resistance-the clinical and molecular spectrum. N Engl J Med326:611-618
10. La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH 1991 Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352:77-79
11. McPhaul MJ 1999 Molecular defects of the androgen receptor. J Steroid Biochem Mol Biol 69:315-322
12. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS 1995 Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 16:271-321
13. Schultz MG 1962 Male pseudohermaphroditism diagnosed with aid of sex chromatin technique. J Am Vet Med Assoc 140:241-244
14. Bardin CW, Bullock L, Schneider G, Allison JE, Stanley AJ 1970 Pseudohermaphrodite rat: end organ insensitivity to testosterone. Science 167:1136-1137
15. Lyon MF, Hawkes SG 1970 X-linked gene for testicular feminization in the mouse. Nature 227:1217-1219
16. Goldstein JL, Wilson JD 1972 Studies on the pathogenesis of the pseudohermaphroditism in the mouse with testicular feminization. J Clin Invest 51:1647-1658
17. Meyers-Wallen VN, Wilson JD, Griffin JE, Fisher S, Moorhead PH, Goldschmidt MH, Haskins ME, Patterson DF 1989 Testicular feminization in a cat. J Am Vet Med Assoc 195:631-634
18. de Kretser DM, Kerr JB 1988 The cytology of the testis. In: Knobil E, Neill JB, Ewing LL, Greenwald GS, Markert CL, Pfaff DW, ed. The physiology of reproduction. New York: Raven Press; 837-932
19. Saez JM 1994 Leydig cells: endocrine, paracrine, and autocrine regulation. Endocr Rev 15:574-626
20. Vogl AW, Pfeiffer DC, Mulholland D, Kimel G, Guttman J 2000 Unique and multifunctional adhesion junctions in the testis: ectoplasmic specializations. Arch Histol Cytol 63:1-15
21. Russell L 1993 Morphological and functional evidence for Sertoligerm cell relationships. In: Russell LD, Griswold MD, eds. The Sertoli cell. Clearwater, FL: Cache River Press; 365-390
22. Mruk DD, Cheng CY 2004 Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev 25: 747-806
23. Griswold MD 1988 Protein secretions of Sertoli cells. Int Rev Cytol 110:133-156
24. Skinner M 1993 Secretion of growth factors and other regulatory factor. In: Russell LD, Griswold MD, eds. The Sertoli cell. Clearwater, FL: Cache River Press; 237-247
25. Waites GM, Gladwell RT 1982 Physiological significance of fluid secretion in the testis and blood-testis barrier. Physiol Rev 62:624-671
26. Skinner MK, Fritz IB 1985 Testicular peritubular cells secrete a protein under androgen control that modulates Sertoli cell functions. Proc Natl Acad Sci USA 82:114-118
27. Norton JN, Skinner MK 1989 Regulation of Sertoli cell function and differentiation through the actions of a testicular paracrine factor P-Mod-S. Endocrinology 124:2711-2719
28. Romano F, Tripiciano A, Muciaccia B, De Cesaris P, Ziparo E, Palombi F, Filippini A 2005 The contractile phenotype of peritubular smooth muscle cells is locally controlled: possible implications in male fertility. Contraception 72:294-297
29. Skinner MK, Schlitz SM, Anthony CT 1989 Regulation of Sertoli cell differentiated function: testicular transferrin and androgenbinding protein expression. Endocrinology 124:3015-3024
30. Anthony CT, Kovacs WJ, Skinner MK 1989 Analysis of the androgen receptor in isolated testicular cell types with a microassay that uses an affinity ligand. Endocrinology 125:2628-2635
31. Sar M, Lubahn DB, French FS, Wilson EM 1990 Immunohistochemical localization of the androgen receptor in rat and human tissues. Endocrinology 127:3180-3186
32. Kimura N, Mizokami A, Oonuma T, Sasano H, Nagura H 1993 Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. J Histochem Cytochem 41:671-678
33. Bremner WJ, Millar MR, Sharpe RM, Saunders PT 1994 Immunohistochemical localization of androgen receptors in the rat testis: evidence for stage-dependent expression and regulation by androgens. Endocrinology 135:1227-1234
34. Vornberger W, Prins G, Musto NA, Suarez-Quian CA 1994 Androgen receptor distribution in rat testis: new implications for androgen regulation of spermatogenesis. Endocrinology 134:2307-2316
35. Zhou X, Kudo A, Kawakami H, Hirano H 1996 Immunohistochemical localization of androgen receptor in mouse testicular germ cells during fetal and postnatal development. Anat Rec 245: 509-518
36. Janssen PJ, Brinkmann AO, Boersma WJ, Van der Kwast TH 1994 Immunohistochemical detection of the androgen receptor with monoclonal antibody F39.4 in routinely processed, paraffinembedded human tissues after microwave pre-treatment. J Histochem Cytochem 42:1169-1175
37. Arenas MI, Royuela M, Lobo MV, Alfaro JM, Fraile B, Paniagua R 2001 Androgen receptor (AR), estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β) expression in the testis of the newt, Triturus marmoratus marmoratus, during the annual cycle. J Anat 199:465-472
38. Solakidi S, Psarra AM, Nikolaropoulos S, Sekeris CE 2005 Estrogen receptors α and β (ERα and ERβ) and androgen receptor (AR) in human sperm: localization of ERβ and AR in mitochondria of the midpiece. Hum Reprod 20:3481-3487
39. Merlet J, Racine C, Moreau E, Moreno SG, Habert R 2007 Male fetal germ cells are targets for androgens that physiologically inhibit their proliferation. Proc Natl Acad Sci USA 104:3615-3620
40. Aquila S, Middea E, Catalano S, Marsico S, Lanzino M, Casaburi I, Barone I, Bruno R, Zupo S, Ando S 2007 Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway. Hum Reprod 22:2594-2605
41. Warikoo PK, Majumdar SS, Allag IS, Das RP, Roy S 1986 Interactions among motility, fertilizing ability, and testosterone binding on spermatozoa of bonnet monkey (Macaca radiata). Arch Androl 16:135-141
42. Galena HJ, Pillai AK, Terner C 1974 Progesterone and androgen receptors in non-flagellate germ cells of the rat testis. J Endocrinol 63:223-237
43. Grootegoed JA, Peters MJ, Mulder E, Rommerts FF, Van der Molen HJ 1977 Absence of a nuclear androgen receptor in isolated germinal cells of rat testis. Mol Cell Endocrinol 9:159-167
44. Suarez-Quian CA, Martinez-Garcia F, Nistal M, Regadera J 1999 Androgen receptor distribution in adult human testis. J Clin Endocrinol Metab 84:350-358
45. Van Roijen JH, Van Assen S, Van Der Kwast TH, De Rooij DG, Boersma WJ, Vreeburg JT, Weber RF 1995 Androgen receptor immunoexpression in the testes of subfertile men. J Androl 16: 510-516
46. Pelletier G, Labrie C, Labrie F 2000 Localization of oestrogen receptor α, oestrogen receptor β and androgen receptors in the rat reproductive organs. J Endocrinol 165:359-370
47. Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X, Xing L, Boyce BF, Hung MC, Zhang S, Gan L, Chang C 2002 Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci USA 99:13498-13503
48. Matsumoto T, Takeyama K, Sato T, Kato S 2003 Androgen receptor functions from reverse genetic models. J Steroid Biochem Mol Biol 85:95-99
49. Holt CL, May GS 1993 A novel phage λ replacement Cre-lox vector that has automatic subcloning capabilities. Gene 133:95-97
50. Chang C, Chen YT, Yeh SD, Xu Q, Wang RS, Guillou F, Lardy H, Yeh S 2004 Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proc Natl Acad Sci USA 101:6876-6881
51. De Gendt K, Swinnen JV, Saunders PT, Schoonjans L, Dewerchin M, Devos A, Tan K, Atanassova N, Claessens F, Lecureuil C, Heyns W, Carmeliet P, Guillou F, Sharpe RM, Verhoeven G 2004 A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA 101:1327-1332
52. Holdcraft RW, Braun RE 2004 Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 131:459-467
53. Wang RS, Yeh S, Chen LM, Lin HY, Zhang C, Ni J, Wu CC, di Sant'Agnese PA, DeMesy-Bentley KL, Tzeng CR, Chang C 2006 Androgen receptor in Sertoli cell is essential for germ cell nursery and junctional complex formation in mouse testes. Endocrinology 147:5624-5633
54. Xu Q, Lin HY, Yeh SD, Yu IC, Wang RS, Chen YT, Zhang C, Altuwaijri S, Chen LM, Chuang KH, Chiang HS, Yeh S, Chang C 2007 Infertility with defective spermatogenesis and steroidogenesis in male mice lacking androgen receptor in Leydig cells. Endocrine 32:96-106
55. Zhang C, Yeh S, Chen YT, Wu CC, Chuang KH, Lin HY, Wang RS, Chang YJ, Mendis-Handagama C, Hu L, Lardy H, Chang C 2006 Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells. Proc Natl Acad Sci USA 103:17718-17723
56. Tsai MY, Yeh SD, Wang RS, Yeh S, Zhang C, Lin HY, Tzeng CR, Chang C 2006 Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. Proc Natl Acad Sci USA 103:18975-18980
57. Stocco DM, Clark BJ 1996 Regulation of the acute production of steroids in steroidogenic cells. Endocr Rev 17:221-244
58. Liu J, Rone MB, Papadopoulos V2006 Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis. J Biol Chem 281:38879-38893
59. Chung BC, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL 1986 Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc Natl Acad Sci USA 83:8962-8966
60. Weusten JJ, Smals AG, Hofman JA, Kloppenborg PW, Benraad TJ 1987 Early time sequence in pregnenolone metabolism to testosterone in homogenates of human and rat testis. Endocrinology 120:1909-1913
61. Fluck CE, Miller WL, Auchus RJ 2003 The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the Δ5 steroidogenic pathway. J Clin Endocrinol Metab 88:3762-3766
62. Fevold HR, Lorence MC, McCarthy JL, Trant JM, Kagimoto M, Waterman MR, Mason JI 1989 Rat P450(17 α) from testis: characterization of a full-length cDNA encoding a unique steroid hydroxylase capable of catalyzing both Δ4- and Δ5-steroid-17,20-lyase reactions. Mol Endocrinol 3:968-975
63. Zhang LH, Rodriguez H, Ohno S, Miller WL 1995 Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc Natl Acad Sci USA 92:10619-10623
64. Pandey AV, Mellon SH, Miller WL 2003 Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17. J Biol Chem 278:2837-2844
65. Luu-The V, Labrie C, Simard J, Lachance Y, Zhao HF, Couet J, Leblanc G, Labrie F 1990 Structure of two in tandem human 17 β-hydroxysteroid dehydrogenase genes. Mol Endocrinol 4:268-275
66. Lorence MC, Corbin CJ, Kamimura N, Mahendroo MS, Mason JI 1990 Structural analysis of the gene encoding human 3 β-hydroxysteroid dehydrogenase/Δ5-4-isomerase. Mol Endocrinol 4:1850-1855
67. Baker PJ, Sha JA, McBride MW, Peng L, Payne AH, O'Shaughnessy PJ 1999 Expression of 3β-hydroxysteroid dehydrogenase type I and type VI isoforms in the mouse testis during development. Eur J Biochem 260:911-917
68. Sriraman V, Sairam MR, Rao AJ 2003 Evaluation of relative roles of LH and FSH in regulation of differentiation of Leydig cells using an ethane 1,2-dimethylsulfonate-treated adult rat model. J Endocrinol 176:151-161
69. Tong MH, Christenson LK, Song WC 2004 Aberrant cholesterol transport and impaired steroidogenesis in Leydig cells lacking estrogen sulfotransferase. Endocrinology 145:2487-2497
70. Huhtaniemi I, Pelliniemi LJ 1992 Fetal Leydig cells: cellular origin, morphology, life span, and special functional features. Proc Soc Exp Biol Med 201:125-140
71. O'Shaughnessy PJ, Baker PJ, Johnston H 2006 The foetal Leydig cell-differentiation, function and regulation. Int J Androl 29:90-95; discussion, 105-108
72. Gondos B 1980 Development and differentiation of the testis and male reproductive tract. In: Steinberger A, Steinberger E, eds. Testicular development, structure and function. New York: Raven Press; 3-20
73. Payne AH, O'Shaughnessy PJ, Chase DJ, Dixon GE, Christensen AK 1982 LH receptors and steroidogenesis in distinct populations of Leydig cells. Ann NY Acad Sci 383:174-203
74. Tilmann C, Capel B 2002 Cellular and molecular pathways regulating mammalian sex determination. Recent Prog Horm Res 57: 1-18
75. Vergouwen RP, Jacobs SG, Huiskamp R, Davids JA, de Rooij DG 1991 Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice. J Reprod Fertil 93: 233-243
76. Dong L, Jelinsky SA, Finger JN, Johnston DS, Kopf GS, Sottas CM, Hardy MP, Ge RS 2007 Gene expression during development of fetal and adult Leydig cells. Ann NY Acad Sci 1120:16-35
77. Vergouwen RP, Huiskamp R, Bas RJ, Roepers-Gajadien HL, Davids JA, de Rooij DG 1993 Postnatal development of testicular cell populations in mice. J Reprod Fertil 99:479-485
78. O'Shaughnessy PJ, Willerton L, Baker PJ 2002 Changes in Leydig cell gene expression during development in the mouse. Biol Reprod 66:966-975
79. Mendis-Handagama SM, Ariyaratne HB 2001 Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod 65:660-671
80. Teerds KJ 1996 Regeneration of Leydig cells after depletion by EDS: a model for postnatal Leydig cell renewal. In: Payne AH, Hardy MP, Russell LD, eds. The Leydig cell. 1st ed. Clearwater, FL: Cache River Press; 203-219
81. O'Shaughnessy PJ, Baker PJ, Johnston H 2005 Neuroendocrine regulation of Leydig cell development. Ann NY Acad Sci 1061: 109-119
82. Sharpe RM 1993 Experimental evidence for Sertoli cell-germ cell and Sertoli cell-Leydig cell interactions. In: Russell LD, Griswold MD, eds. The Sertoli cell. 1st ed. Clearwater, FL: Cache River Press; 391-419
83. Saez JM, Lejeune H 1996 Regulation of Leydig cell functions by hormones and growth factors other than LH and IGF-1. In: Payne AH, Hardy MP, Russell LD, eds. The Leydig cell. 1st ed. Clearwater, FL: Cache River Press; 383-406
84. Teerds KJ, de Rooij DG, de Jong FH, van Haaster LH 1998 Development of the adult-type Leydig cell population in the rat is affected by neonatal thyroid hormone levels. Biol Reprod 59:344-350
85. Ariyaratne HB, Mills N, Mason JI, Mendis-Handagama SM 2000 Effects of thyroid hormone on Leydig cell regeneration in the adult rat following ethane dimethane sulphonate treatment. Biol Reprod 63:1115-1123
86. Abney TO 1999 The potential roles of estrogens in regulating Leydig cell development and function: a review. Steroids 64:610-617
87. Ge RS, Shan LX, Hardy MP 1996 Pubertal development of Leydig cells. In: Payne AH, Hardy MP, Russell LD, eds. The Leydig cell. 1st ed. Clearwater, FL: Cache River Press; 159-172
88. Hardy MP, Kelce WR, Klinefelter GR, Ewing LL 1990 Differentiation of Leydig cell precursors in vitro: a role for androgen. Endocrinology 127:488-490
89. Murphy L, Jeffcoate IA, O'Shaughnessy PJ 1994 Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse. Endocrinology 135:1372-1377
90. Jones RD, Pugh PJ, Hall J, Channer KS, Jones TH 2003 Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse. Eur J Endocrinol 148: 111-120
91. Murphy L, O'Shaughnessy PJ 1991 Testicular steroidogenesis in the testicular feminized (Tfm) mouse: loss of 17 α-hydroxylase activity. J Endocrinol 131:443-449
92. O'Shaughnessy PJ, Johnston H, Willerton L, Baker PJ 2002 Failure of normal adult Leydig cell development in androgen-receptordeficient mice. J Cell Sci 115:3491-3496
93. Blackburn WR, Chung KW, Bullock L, Bardin CW1973 Testicular feminization in the mouse: studies of Leydig cell structure and function. Biol Reprod 9:9-23
94. De Gendt K, Atanassova N, Tan KA, de Franca LR, Parreira GG, McKinnell C, Sharpe RM, Saunders PT, Mason JI, Hartung S, Ivell R, Denolet E, Verhoeven G 2005 Development and function of the adult generation of Leydig cells in mice with Sertoli cellselective or total ablation of the androgen receptor. Endocrinology 146:4117-4126
95. Morris JM, Mahesh VB 1963 Further observations on the syndrome, "testicular feminization." Am J Obstet Gynecol 87:731-748
96. Savage MO, Chaussain JL, Evain D, Roger M, Canlorbe P, Job JC 1978 Endocrine studies in male pseudohermaphroditism in childhood and adolescence. Clin Endocrinol (Oxf) 8:219-231
97. Migeon CJ, Berkovitz GD, Brown TR 1994 Sexual differentiation and ambiguity. In: Kappy MS, Blizzard RM, Migeon CJ, eds. The diagnosis and treatment of endocrine disorders in childhood and adolescence. Springfield, IL: Thomas; 573-716
98. Hutson JM, Hasthorpe S, Heyns CF 1997 Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev 18:259-280
99. Tong SY, Hutson JM, Watts LM 1996 Does testosterone diffuse down the Wolffian duct during sexual differentiation? J Urol 155: 2057-2059
100. Wilson JD, George FW, Griffin JE 1981 The hormonal control of sexual development. Science 211:1278-1284
101. Ivell R, Hartung S 2003 The molecular basis of cryptorchidism. Mol Hum Reprod 9:175-181
102. Foresta C, Zuccarello D, Garolla A, Ferlin A 2008 Role of hormones, genes, and environment in human cryptorchidism. Endocr Rev 29:560-580
103. Klonisch T, Fowler PA, Hombach-Klonisch S 2004 Molecular and genetic regulation of testis descent and external genitalia development. Dev Biol 270:1-18
104. Hutson JM 1986 Testicular feminization: a model for testicular descent in mice and men. J Pediatr Surg 21:195-198
105. Sharpe RM, McKinnell C, Kivlin C, Fisher JS 2003 Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125:769-784
106. Johnson L, Zane RS, Petty CS, Neaves WB 1984 Quantification of the human Sertoli cell population: its distribution, relation to germ cell numbers, and age-related decline. Biol Reprod 31:785-795
107. Orth JM, Gunsalus GL, Lamperti AA 1988 Evidence from Sertoli cell-depleted rats indicates that spermatid number in adults depends on numbers of Sertoli cells produced during perinatal development. Endocrinology 122:787-794
108. Baker PJ, O'Shaughnessy PJ 2001 Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development in mice. Reproduction 122:227-234
109. Johnston H, Baker PJ, Abel M, Charlton HM, Jackson G, Fleming L, Kumar TR, O'Shaughnessy PJ 2004 Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse. Endocrinology 145: 318-329
110. Holsberger DR, Cooke PS 2005 Understanding the role of thyroid hormone in Sertoli cell development: a mechanistic hypothesis. Cell Tissue Res 322:133-140
111. Hill CM, Anway MD, Zirkin BR, Brown TR 2004 Intratesticular androgen levels, androgen receptor localization, and androgen receptor expression in adult rat Sertoli cells. Biol Reprod 71:1348-1358
112. McKinnell C, Saunders PT, Fraser HM, Kelnar CJ, Kivlin C, Morris KD, Sharpe RM 2001 Comparison of androgen receptor and oestrogen receptor β immunoexpression in the testes of the common marmoset (Callithrix jacchus) from birth to adulthood: low androgen receptor immunoexpression in Sertoli cells during the neonatal increase in testosterone concentrations. Reproduction 122: 419-429
113. Majdic G, Millar MR, Saunders PT 1995 Immunolocalisation of androgen receptor to interstitial cells in fetal rat testes and to mesenchymal and epithelial cells of associated ducts. J Endocrinol 147:285-293
114. You L, Sar M 1998 Androgen receptor expression in the testes and epididymides of prenatal and postnatal Sprague-Dawley rats. Endocrine 9:253-261
115. Warren DW, Haltmeyer GC, Eik-Nes KB 1973 Testosterone in the fetal rat testis. Biol Reprod 8:560-565
116. Feldman SC, Bloch E 1978 Developmental pattern of testosterone synthesis by fetal rat testes in response to luteinizing hormone. Endocrinology 102:999-1007
117. Zhou Q, Shima JE, Nie R, Friel PJ, Griswold MD 2005 Androgenregulated transcripts in the neonatal mouse testis as determined through microarray analysis. Biol Reprod 72:1010-1019
118. Atanassova NN, Walker M, McKinnell C, Fisher JS, Sharpe RM 2005 Evidence that androgens and oestrogens, as well as folliclestimulating hormone, can alter Sertoli cell number in the neonatal rat. J Endocrinol 184:107-117
119. Mu X, Liu K, Kleymenova E, Sar M, Young SS, Gaido KW 2006 Gene expression profiling of androgen receptor antagonists in the rat fetal testis reveals few common gene targets. J Biochem Mol Toxicol 20:7-17
120. Tan KA, De Gendt K, Atanassova N, Walker M, Sharpe RM, Saunders PT, Denolet E, Verhoeven G 2005 The role of androgens in Sertoli cell proliferation and functional maturation: studies in mice with total or Sertoli cell-selective ablation of the androgen receptor. Endocrinology 146:2674-2683
121. Weinbauer GF, Nieschlag E 1993 Hormonal control of spermatogenesis. In: de Kretser D, ed. Molecular biology of the male reproductive system. San Diego: Academic Press Inc.; 101-142
122. Singh J, O'Neill C, Handelsman DJ 1995 Induction of spermatogenesis by androgens in gonadotropin-deficient (hpg) mice. Endocrinology 136:5311-5321
123. Singh J, Handelsman DJ 1996 The effects of recombinant FSH on testosterone-induced spermatogenesis in gonadotrophin-deficient (hpg) mice. J Androl 17:382-393
124. Haywood M, Spaliviero J, Jimemez M, King NJ, Handelsman DJ, Allan CM 2003 Sertoli and germ cell development in hypogonadal (hpg) mice expressing transgenic follicle-stimulating hormone alone or in combination with testosterone. Endocrinology 144:509-517
125. Ghosh S, Sinha-Hikim AP, Russell LD 1991 Further observations of stage-specific effects seen after short-term hypophysectomy in the rat. Tissue Cell 23:613-630
126. Kerr JB, Maddocks S,SharpeRM 1992 Testosterone and FSH have independent, synergistic and stage-dependent effects upon spermatogenesis in the rat testis. Cell Tissue Res 268:179-189
127. Franca LR, Parreira GG, Gates RJ, Russell LD 1998 Hormonal regulation of spermatogenesis in the hypophysectomized rat: quantitation of germ-cell population and effect of elimination of residual testosterone after long-term hypophysectomy. J Androl 19:335-340; discussion, 341-332
128. Hannema SE, Scott IS, Rajpert-De Meyts E, Skakkebaek NE, Coleman N, Hughes IA 2006 Testicular development in the complete androgen insensitivity syndrome. J Pathol 208:518-527
129. Denolet E, De Gendt K, Allemeersch J, Engelen K, Marchal K, Van Hummelen P, Tan KA, Sharpe RM, Saunders PT, Swinnen JV, Verhoeven G 2006 The effect of a Sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Mol Endocrinol 20:321-334
130. Eacker SM, Shima JE, Connolly CM, Sharma M, Holdcraft RW, Griswold MD, Braun RE 2007 Transcriptional profiling of androgen receptor (AR) mutants suggests instructive and permissive roles of AR signaling in germ cell development. Mol Endocrinol 21:895-907
131. McLachlan RI, Wreford NG, Meachem SJ, De Kretser DM, Robertson DM 1994 Effects of testosterone on spermatogenic cell populations in the adult rat. Biol Reprod 51:945-955
132. O'Donnell L, McLachlan RI, Wreford NG, Robertson DM 1994 Testosterone promotes the conversion of round spermatids between stages VII and VIII of the rat spermatogenic cycle. Endocrinology 135:2608-2614
133. Hales DB, Sha LL, Payne AH 1987 Testosterone inhibits cAMP- induced de novo synthesis of Leydig cell cytochrome P-450(17 a) by an androgen receptor-mediated mechanism. J Biol Chem 262: 11200-11206
134. Lyon MF, Glenister PH, Lamoreux ML 1975 Normal spermatozoa from androgen-resistant germ cells of chimaeric mice and the role of androgen in spermatogenesis. Nature 258:620-622
135. Johnston DS, Russell LD, Friel PJ, Griswold MD 2001 Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 142:2405-2408
136. Justrabo E, Cabanne F, Michiels R, Bastien H, Dusserre P, Pansiot F, Cayot F 1978 A complete form of testicular feminisation syndrome; a light and electron microscopy study. J Pathol 126:165-171
137. Rutgers JL, Scully RE 1991 The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases. Int J Gynecol Pathol 10:126-144
138. Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD 1998 Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 95:13726-13731