Tissue- and cell-specific functions of the androgen receptor revealed through conditional knockout models in mice

Molecular and Cellular Endocrinology

Volumn 352, Issue 1-2, 2012, Pages 13-25

  De Gendt, Karel ^a   Verhoeven, Guido ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Androgen; Androgen receptor; Cell selective; Cre loxP; Knockout; Testosterone

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; CRE RECOMBINASE; ESTRADIOL; ESTROGEN RECEPTOR;

ACCESSORY SEX GLAND; ADIPOSE TISSUE; ALLELE; BONE DEVELOPMENT; CELL INTERACTION; CELL SPECIFICITY; EPIDIDYMIS; EPITHELIUM CELL; FEMALE FERTILITY; GENE INACTIVATION; GENE TECHNOLOGY; GENETIC RECOMBINATION; GENITAL SYSTEM FUNCTION; HORMONE ACTION; HOST RESISTANCE; KNOCKOUT MOUSE; LEYDIG CELL; LIPID STORAGE; MALE FERTILITY; MESENCHYME CELL; MOUSE STRAIN; MUSCLE FUNCTION; NONHUMAN; PERITUBULAR MYOID CELL; PRIORITY JOURNAL; PROSTATE; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SEMINAL VESICLE; SERTOLI CELL; SEX DIFFERENCE; SEXUAL BEHAVIOR; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; TESTIS; TESTIS CELL; TISSUE SPECIFICITY; TRANSGENIC MOUSE; WOUND HEALING;

ANIMALS; MICE; MICE, KNOCKOUT; ORGAN SPECIFICITY; RECEPTORS, ANDROGEN; SIGNAL TRANSDUCTION;

EID: 84857363883     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2011.08.008     Document Type: Review

References (113)

1. Ashcroft G.S., Mills S.J. Androgen receptor-mediated inhibition of cutaneous wound healing. J. Clin. Invest 2002, 110:615-624.
2. Berton T.R., Matsumoto T., Page A., Conti C.J., Deng C.X., Jorcano J.L., Johnson D.G. Tumor formation in mice with conditional inactivation of Brca1 in epithelial tissues. Oncogene 2003, 22:5415-5426.
3. Bhowmick N.A., Chytil A., Plieth D., Gorska A.E., Dumont N., Shappell S., Washington M.K., Neilson E.G., Moses H.L. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 2004, 303:848-851.
4. Bonthuis P.J., Cox K.H., Searcy B.T., Kumar P., Tobet S., Rissman E.F. Of mice and rats: key species variations in the sexual differentiation of brain and behavior. Front. Neuroendocrinol. 2010, 31:341-358.
5. Bremner W.J., Millar M.R., Sharpe R.M., Saunders P.T.K. Immunohistochemical localization of androgen receptors in the rat testis - evidence for stage-dependent expression and regulation by androgens. Endocrinology 1994, 135:1227-1234.
6. Brüning J.C., Michael M.D., Winnay J.N., Hayashi T., Horsch D., Accili D., Goodyear L.J., Kahn C.R. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol. Cell 1998, 2:559-569.
7. Callewaert F., Boonen S., Vanderschueren D. Sex steroids and the male skeleton: a tale of two hormones. Trends Endocrinol. Metab. 2010, 21:89-95.
8. Callewaert F., Sinnesael M., Gielen E., Boonen S., Vanderschueren D. Skeletal sexual dimorphism: relative contribution of sex steroids, GH-IGF1, and mechanical loading. J. Endocrinol. 2010, 207:127-134.
9. Callewaert F., Venken K., Ophoff J., De G.K., Torcasio A., van Lenthe G.H., Van O.H., Boonen S., Bouillon R., Verhoeven G., Vanderschueren D. Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-alpha. FASEB J. 2009, 23:232-240.
10. Chambon C., Duteil D., Vignaud A., Ferry A., Messaddeq N., Malivindi R., Kato S., Chambon P., Metzger D. Myocytic androgen receptor controls the strength but not the mass of limb muscles. Proc. Natl. Acad. Sci. USA 2010, 107:14327-14332.
11. Chang C.S., Chen Y.T., Yeh S.D., Xu Q.Q., Wang R.S., Guillou F., Lardy H., Yeh S.Y. Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proc. Natl. Acad. Sci. USA 2004, 101:6876-6881.
12. Chiang C., Chiu M., Moore A.J., Anderson P.H., Ghasem-Zadeh A., McManus J.F., Ma C., Seeman E., Clemens T.L., Morris H.A., Zajac J.D., Davey R.A. Mineralization and bone resorption are regulated by the androgen receptor in male mice. J. Bone Miner. Res. 2009, 24:621-631.
13. Clausen B.E., Burkhardt C., Reith W., Renkawitz R., Forster I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 1999, 8:265-277.
14. Cunha G.R., Ricke W., Thomson A., Marker P.C., Risbridger G., Hayward S.W., Wang Y.Z., Donjacour A.A., Kurita T. Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development. J. Steroid Biochem. Mol. Biol. 2004, 92:221-236.
15. De Gendt K., Atanassova N., Tan K.A., De França L.R., Parreira G.G., Mckinnell C., Sharpe R.M., Saunders P.T.K., Mason J.I., Hartung S., Ivell R., Denolet E., Verhoeven G. Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor. Endocrinology 2005, 146:4117-4126.
16. De Gendt K., Swinnen J.V., Saunders P.T.K., Schoonjans L., Dewerchin M., Devos A., Tan K., Atanassova N., Claessens F., Lecureuil C., Heyns W., Carmeliet P., Guillou F., Sharpe R.M., Verhoeven G. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc. Natl. Acad. Sci. USA 2004, 101:1327-1332.
17. De Gendt K., Verhoeven G. Tissue-selective knockouts of steroid receptors: a novel paradigm in the study of steroid action. Methods in Molecular Biology: The Nuclear Receptor Superfamily 2009, 237-261. Humana Press, New York. I.J. McEwan (Ed.).
18. Denolet E., De Gendt K., Allemeersch J., Engelen K., Marchal K., Van Hummelen P., Tan K.A., Sharpe R.M., Saunders P.T.K., Swinnen J.V., Verhoeven G. The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Mol. Endocrinol. 2006, 20:321-334.
19. Eacker S.M., Shima J.E., Connolly C.M., Sharma M., Holdcraft R.W., Griswold M.D., Braun R.E. Transcriptional profiling of androgen receptor (AR) mutants suggests instructive and permissive roles of AR signaling in germ cell development. Mol. Endocrinol. 2007, 21:895-907.
20. Fan W., Yanase T., Nomura M., Okabe T., Goto K., Sato T., Kawano H., Kato S., Nawata H. Androgen receptor null male mice develop late-onset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion. Diabetes 2005, 54:1000-1008.
21. Frutkin A.D., Shi H., Otsuka G., Leveen P., Karlsson S., Dichek D.A. A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre. J. Mol. Cell Cardiol. 2006, 41:724-731.
22. Grootegoed J.A., Peters M.J., Mulder E., Rommerts F.F.G., Vandermolen H.J. Absence of A nuclear androgen receptor in isolated germinal cells of rat testis. Mol. Cell. Endocrinol. 1977, 9:159-167.
23. Hamson D.K., Jordan C.L., Breedlove S.M. The testosterone two-step is really a minuet. Neuron 2010, 66:167-169.
24. Hardy M.P., Kelce W.R., Klinefelter G.R., Ewing L.L. Differentiation of Leydig-cell precursors in vitro - a role for androgen. Endocrinology 1990, 127:488-490.
25. Hébert J.M., McConnell S.K. Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures. Dev. Biol. 2000, 222:296-306.
26. Holdcraft R.W., Braun R.E. Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 2004, 131:459-467.
27. Holtwick R., Gotthardt M., Skryabin B., Steinmetz M., Potthast R., Zetsche B., Hammer R.E., Herz J., Kuhn M. Smooth muscle-selective deletion of guanylyl cyclase-A prevents the acute but not chronic effects of ANP on blood pressure. Proc. Natl. Acad. Sci. USA 2002, 99:7142-7147.
28. Honda S., Harada N., Ito S., Takagi Y., Maeda S. Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene. Biochem. Biophys. Res. Commun. 1998, 252:445-449.
29. Hu Y.C., Wang P.H., Yeh S., Wang R.S., Xie C., Xu Q., Zhou X., Chao H.T., Tsai M.Y., Chang C. Subfertility and defective folliculogenesis in female mice lacking androgen receptor. Proc. Natl. Acad. Sci. USA 2004, 101:11209-11214.
30. Jamin S.P., Arango N.A., Mishina Y., Hanks M.C., Behringer R.R. Requirement of Bmpr1a for Mullerian duct regression during male sexual development. Nat. Genet. 2002, 32:408-410.
31. Jeyasuria P., Ikeda Y., Jamin S.P., Zhao L.P., De Rooij D.G., Themmen A.P.N., Behringer R.R., Parker K.L. Cell-specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Mol. Endocrinol. 2004, 18:1610-1619.
32. Jin C., McKeehan K., Wang F. Transgenic mouse with high Cre recombinase activity in all prostate lobes, seminal vesicle, and ductus deferens. Prostate 2003, 57:160-164.
33. Johnston D.S., Russell L.D., Friel P.J., Griswold M.D. Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 2001, 142:2405-2408.
34. Juntti S.A., Tollkuhn J., Wu M.V., Fraser E.J., Soderborg T., Tan S., Honda S., Harada N., Shah N.M. The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors. Neuron 2010, 66:260-272.
35. Kato S. Androgen receptor structure and function from knock-out mouse. Clinical Pediatric Endocrinology 2002, 11:1-7.
36. Kawano H., Sato T., Yamada T., Matsumoto T., Sekine K., Watanabe T., Nakamura T., Fukuda T., Yoshimura K., Yoshizawa T., Aihara K., Yamamoto Y., Nakamichi Y., Metzger D., Chambon P., Nakamura K., Kawaguchi H., Kato S. Suppressive function of androgen receptor in bone resorption. Proc. Natl. Acad. Sci. USA 2003, 100:9416-9421.
37. Krutskikh A., De G.K., Sharp V., Verhoeven G., Poutanen M., Huhtaniemi I. Targeted inactivation of the androgen receptor gene in murine proximal epididymis causes epithelial hypotrophy and obstructive azoospermia. Endocrinology 2010.
38. Kyronlahti A., Euler R., Bielinska M., Schoeller E.L., Moley K.H., Toppari J., Heikinheimo M., Wilson D.B. GATA4 regulates Sertoli cell function and fertility in adult male mice. Mol. Cell Endocrinol. 2011, 333:85-95.
39. Lai J.J., Lai K.P., Chuang K.H., Chang P., Yu I.C., Lin W.J., Chang C. Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-alpha expression. J. Clin. Invest. 2009, 119:3739-3751.
40. Lan Z.J., Xu X., Cooney A.J. Differential oocyte-specific expression of Cre recombinase activity in GDF-9-iCre, Zp3cre, and Msx2Cre transgenic mice. Biol. Reprod. 2004, 71:1469-1474.
41. Lecureuil C., Fontaine I., Crepieux P., Guillou F. Sertoli and granulosa cell-specific Cre recombinase activity in transgenic mice. Genesis 2002, 33:114-118.
42. Lim P., Robson M., Spaliviero J., McTavish K.J., Jimenez M., Zajac J.D., Handelsman D.J., Allan C.M. Sertoli cell androgen receptor DNA binding domain is essential for the completion of spermatogenesis. Endocrinology 2009, 150:4755-4765.
43. Lin H.Y., Xu Q., Yeh S., Wang R.S., Sparks J.D., Chang C. Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes 2005, 54:1717-1725.
44. Lin H.Y., Yu I.C., Wang R.S., Chen Y.T., Liu N.C., Altuwaijri S., Hsu C.L., Ma W.L., Jokinen J., Sparks J.D., Yeh S., Chang C. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology 2008, 47:1924-1935.
45. Liu F., Woitge H.W., Braut A., Kronenberg M.S., Lichtler A.C., Mina M., Kream B.E. Expression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues. Int. J. Dev. Biol. 2004, 48:645-653.
46. Lyon, M.F., Glenister, P.H., 1980. Reduced reproductive-performance in androgen-resistant tfm-tfm female mice. Proceedings of the Royal Society of London Series B-Biological Sciences 208, 1-12.
47. MacLean H.E., Chiu W.S., Ma C., McManus J.F., Davey R.A., Cameron R., Notini A.J., Zajac J.D. A floxed allele of the androgen receptor gene causes hyperandrogenization in male mice. Physiol. Genomics 2008, 33:133-137.
48. MacLean H.E., Chiu W.S., Notini A.J., Axell A.M., Davey R.A., McManus J.F., Ma C., Plant D.R., Lynch G.S., Zajac J.D. Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice. FASEB J. 2008, 22:2676-2689.
49. MacLean H.E., Handelsman D.J. Unraveling androgen action in muscle: genetic tools probing cellular mechanisms. Endocrinology 2009, 150:3437-3439.
50. MacLean H.E., Moore A.J., Sastra S.A., Morris H.A., Ghasem-Zadeh A., Rana K., Axell A.M., Notini A.J., Handelsman D.J., Seeman E., Zajac J.D., Davey R.A. DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females. J. Endocrinol. 2010, 206:93-103.
51. Matsumoto T., Shiina H., Kawano H., Sato T., Kato S. Androgen receptor functions in male and female physiology. J. Steroid Biochem. Mol. Biol. 2008, 109:236-241.
52. McLachlan R.I., O'Donnell L., Meachem S.J., Stanton P.G., de Kretser D.M., Pratis K., Robertson D.M. Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man. Recent Prog. Horm. Res. 2002, 57:149-179.
53. Meng J., Holdcraft R.W., Shima J.E., Griswold M.D., Braun R.E. Androgens regulate the permeability of the blood-tests barrier. Proc. Natl. Acad. Sci. USA 2005, 102:16696-16700.
54. Metzger D., Chambon P. Site- and time-specific gene targeting in the mouse. Methods 2001, 24:71-80.
55. Miniou P., Tiziano D., Frugier T., Roblot N., Le M.M., Melki J. Gene targeting restricted to mouse striated muscle lineage. Nucleic Acids Res. 1999, 27:e27-e30.
56. Nagy A. Cre recombinase: the universal reagent for genome tailoring. Genesis 2000, 26:99-109.
57. Niu Y., Altuwaijri S., Lai K.P., Wu C.T., Ricke W.A., Messing E.M., Yao J., Yeh S., Chang C. Androgen receptor is a tumor suppressor and proliferator in prostate cancer. Proc. Natl. Acad. Sci. USA 2008, 105:12182-12187.
58. Niu Y., Altuwaijri S., Yeh S., Lai K.P., Yu S., Chuang K.H., Huang S.P., Lardy H., Chang C. Targeting the stromal androgen receptor in primary prostate tumors at earlier stages. Proc. Natl. Acad. Sci. USA 2008, 105:12188-12193.
59. Niu Y., Chang T.M., Yeh S., Ma W.L., Wang Y.Z., Chang C. Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails. Oncogene 2010, 29:3593-3604.
60. Notini A.J., Davey R.A., McManus J.F., Bate K.L., Zajac J.D. Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model. J. Mol. Endocrinol. 2005, 35:547-555.
61. Notini A.J., McManus J.F., Moore A., Bouxsein M., Jimenez M., Chiu W.S., Glatt V., Kream B.E., Handelsman D.J., Morris H.A., Zajac J.D., Davey R.A. Osteoblast deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice. J. Bone Miner. Res. 2007, 22:347-356.
62. O'Hara L., Welsh M., Saunders P.T., Smith L.B. Androgen receptor expression in the caput epididymal epithelium is essential for development of the initial segment and epididymal spermatozoa transit. Endocrinology 2010.
63. O'Shaughnessy P.J., Abel M., Charlton H.M., Hu B., Johnston H., Baker P.J. Altered expression of genes involved in regulation of vitamin A metabolism, solute transportation, and cytoskeletal function in the androgen-insensitive tfm mouse testis. Endocrinology 2007, 148:2914-2924.
64. O'Shaughnessy P.J., Johnston H., Willerton L., Baker P.J. Failure of normal adult Leydig cell development in androgen-receptor-deficient mice. J. Cell Sci. 2002, 115:3491-3496.
65. Ogawa S., Chester A.E., Hewitt S.C., Walker V.R., Gustafsson J.A., Smithies O., Korach K.S., Pfaff D.W. Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO). Proc. Natl. Acad. Sci. USA 2000, 97:14737-14741.
66. Ohno S., Christian L., Attardi B. Role of testosterone in normal female function. Nature-New Biology 1973, 243:119-120.
67. Ophoff J., Van P.K., Callewaert F., De G.K., De B.K., Vanden Bosch A., Verhoeven G., Hespel P., Vanderschueren D. Androgen signaling in myocytes contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. Endocrinology 2009, 150:3558-3566.
68. Phoenix C.H., Goy R.W., Gerall A.A., Young W.C. Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 1959, 65:369-382.
69. Postic C., Shiota M., Niswender K.D., Jetton T.L., Chen Y., Moates J.M., Shelton K.D., Lindner J., Cherrington A.D., Magnuson M.A. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J. Biol. Chem. 1999, 274:305-315.
70. Raskin K., De G.K., Duittoz A., Liere P., Verhoeven G., Tronche F., Mhaouty-Kodja S. Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses. J. Neurosci. 2009, 29:4461-4470.
71. Robaire B., Hinton B.T., Orgebin-Crist M.C. The epididymis. Knobil and Neilly's physiology of reproduction 2006, 1071-1148. Elsevier Academic Press, San Diego. J.D. Neill (Ed.).
72. Sato T., Matsumoto T., Kawano H., Watanabe T., Uematsu Y., Sekine K., Fukuda T., Aihara K.I., Krust A., Yamada T., Nakamichi Y., Yamamoto Y., Nakamura T., Yoshimura K., Yoshizawa T., Metzger D., Chambon P., Kato S. Brain masculinization requires androgen receptor function. Proc. Natl. Acad. Sci. USA 2004, 101:1673-1678.
73. Sato T., Matsumoto T., Yamada T., Watanabe T., Kawano H., Kato S. Late onset of obesity in male androgen receptor-deficient (AR KO) mice. Biochem. Biophys. Res. Commun. 2003, 300:167-171.
74. Sen A., Hammes S.R. Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Mol. Endocrinol. 2010, 24:1393-1403.
75. Shiina H., Matsumoto T., Sato T., Igarashi K., Miyamoto J., Takemasa S., Sakari M., Takada I., Nakamura T., Metzger D., Chambon P., Kanno J., Yoshikawa H., Kato S. Premature ovarian failure in androgen receptor-deficient mice. Proc. Natl. Acad. Sci. USA 2006, 103:224-229.
76. Simanainen U., Allan C.M., Lim P., McPherson S., Jimenez M., Zajac J.D., Davey R.A., Handelsman D.J. Disruption of prostate epithelial androgen receptor impedes prostate lobe-specific growth and function. Endocrinology 2007, 148:2264-2272.
77. Simanainen U., McNamara K., Davey R.A., Zajac J.D., Handelsman D.J. Severe subfertility in mice with androgen receptor inactivation in sex accessory organs but not in testis. Endocrinology 2008, 149:3330-3338.
78. Simanainen U., McNamara K., Gao Y.R., Handelsman D.J. Androgen sensitivity of prostate epithelium is enhanced by postnatal androgen receptor inactivation. Am. J. Physiol. Endocrinol. Metab. 2009, 296:E1335-E1343.
79. Singh J., Oneill C., Handelsman D.J. Induction of spermatogenesis by androgens in gonadotropin-deficient (Hpg) mice. Endocrinology 1995, 136:5311-5321.
80. Skinner M.K. Cell-cell interactions in the testis. Endocr. Rev. 1991, 12:45-77.
81. Smith L. Good planning and serendipity: exploiting the Cre/Lox system in the testis. Reproduction 2011, 141:151-161.
82. Tan K.A., De Gendt K., Atanassova N., Walker M., Sharpe R.M., Saunders P.T.K., Denolet E., Verhoeven G. 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 2005, 146:2674-2683.
83. Teixeira J., Maheswaran S., Donahoe P.K. Mullerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications. Endocr. Rev. 2001, 22:657-674.
84. Tronche F., Kellendonk C., Kretz O., Gass P., Anlag K., Orban P.C., Bock R., Klein R., Schutz G. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat. Genet. 1999, 23:99-103.
85. Tsai M.Y., Yeh S.D., Wang R.S., Yeh S., Zhang C., Lin H.Y., Tzeng C.R., Chang C. Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. Proc. Natl. Acad. Sci. USA. 2006, 103:18975-18980.
86. Urs S., Harrington A., Liaw L., Small D. Selective expression of an aP2/fatty acid binding protein 4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Res. 2006, 15:647-653.
87. Verhoeven G., Denolet E., Swinnen J.V., Willems A., Claessens F., Saunders P.T.K., Sharpe R.M., De Gendt K. Contribution of recent transgenic models and transcriptional profiling studies to our understanding of the mechanisms by which androgens control spermatogenesis. Immunol., Endocr. Metab. Agents Med. Chem. 2008, 8:2-13.
88. Verhoeven G., Denolet E., Swinnen J.V., Willems A., Saunders P.T.K., Sharpe R.M., De Gendt K. The role of androgens in the control of spermatogenesis: lessons from transgenic models involving a Sertoli cell-selective knockout of the androgen receptor. Anim. Reprod. 2007, 4:3-14.
89. Verhoeven G., Hoeben E., De Gendt K. Peritubular cell-Sertoli cell interactions: factors involved in PmodS activity. Andrologia 2000, 32:42-45.
90. Verhoeven G., Swinnen J.V. Indirect mechanisms and cascades of androgen action. Mol. Cell. Endocrinol. 1999, 151:205-212.
91. Verhoeven G., Willems A., Denolet E., Swinnen J.V., De G.K. Androgens and spermatogenesis: lessons from transgenic mouse models. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2010, 365:1537-1556.
92. Vidal F., Sage J., Cuzin F., Rassoulzadegan M. Cre expression in primary spermatocytes: a tool for genetic engineering of the germ line. Mol. Reprod. Dev. 1998, 51:274-280.
93. Walters K.A., McTavish K.J., Seneviratne M.G., Jimenez M., McMahon A.C., Allan C.M., Salamonsen L.A., Handelsman D.J. Subfertile female androgen receptor knockout mice exhibit defects in neuroendocrine signaling, intraovarian function, and uterine development but not uterine function. Endocrinology 2009, 150:3274-3282.
94. Walters K.A., Simanainen U., Handelsman D.J. Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models. Hum. Reprod. Update 2010, 16:543-558.
95. Wang R.S., Yeh S., Chen L.M., Lin H.Y., Zhang C.X., Ni J., Wu C.C., di Sant'Agnese P.A., DeMesy-Bentley K.L., Tzeng C.R., Chang C.S. Androgen receptor in Sertoli cell is essential for germ cell nursery and junctional complex formation in mouse testes. Endocrinology 2006, 147:5624-5633.
96. Wang R.S., Yeh S., Tzeng C.R., Chang C. Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice. Endocr. Rev. 2009, 30:119-132.
97. Welsh M., Moffat L., Jack L., McNeilly A., Brownstein D., Saunders P.T., Sharpe R.M., Smith L.B. Deletion of androgen receptor in the smooth muscle of the seminal vesicles impairs secretory function and alters its responsiveness to exogenous testosterone and estradiol. Endocrinology 2010, 151:3374-3385.
98. Welsh M., Saunders P.T., Atanassova N., Sharpe R.M., Smith L.B. Androgen action via testicular peritubular myoid cells is essential for male fertility. FASEB J. 2009, 23:4218-4230.
99. Welsh M., Saunders P.T., Fisken M., Scott H.M., Hutchison G.R., Smith L.B., Sharpe R.M. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J. Clin. Invest. 2008, 118:1479-1490.
100. Welsh, M., Sharpe, R.M., Moffat, L., Atanassova, N., Saunders, P.T., Kilter, S., Bergh, A., Smith, L.B., 2010b. Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics. PLoS. One. 5, e13632.
101. Willems, A., Batlouni, S.R., Esnal, A., Swinnen, J.V., Saunders, P.T., Sharpe, R.M., Franca, L.R., De, G.K., Verhoeven, G., 2010. Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development. PLoS. One. 5, e14168.
102. Wilson J.D. Metabolism of testicular androgens. Handbook of Physiology, Section 7, volume V, Endocrinology 1975, 143-172. Williams &Wilkins Co, Baltimore, Maryland. D.W. Hamilton, R.O. Greep (Eds.).
103. Wu C.T., Altuwaijri S., Ricke W.A., Huang S.P., Yeh S., Zhang C., Niu Y., Tsai M.Y., Chang C. Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor. Proc. Natl. Acad. Sci. USA 2007, 104:12679-12684.
104. Wu X., Wu J., Huang J., Powell W.C., Zhang J., Matusik R.J., Sangiorgi F.O., Maxson R.E., Sucov H.M., Roy-Burman P. Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech. Dev. 2001, 101:61-69.
105. Xin H.B., Deng K.Y., Rishniw M., Ji G., Kotlikoff M.I. Smooth muscle expression of Cre recombinase and eGFP in transgenic mice. Physiol. Genomics 2002, 10:211-215.
106. Xu Q., Lin H.Y., Yeh S.D., Yu I.C., Wang R.S., Chen Y.T., Zhang C., Altuwaijri S., Chen L.M., Chuang K.H., Chiang H.S., Yeh S., Chang C. Infertility with defective spermatogenesis and steroidogenesis in male mice lacking androgen receptor in Leydig cells. Endocr. 2007, 32:96-106.
107. Yeh S.Y., Tsai M.Y., Xu Q.Q., Mu X.M., Lardy H., Huang K.E., Lin H., Yeh S.D., Altuwaijri S., Zhou X.C., Xing L.P., Boyce B.F., Hung M.C., Zhang S., Gan L., Chang C.S. 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 2002, 99:13498-13503.
108. Yu I.C., Lin H.Y., Liu N.C., Wang R.S., Sparks J.D., Yeh S., Chang C. Hyperleptinemia without obesity in male mice lacking androgen receptor in adipose tissue. Endocrinology 2008, 149:2361-2368.
109. Yu S., Zhang C., Lin C.C., Niu Y., Lai K.P., Chang H.C., Yeh S.D., Chang C., Yeh S. Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells. Prostate 2010.
110. Zhang C.X., Yeh S.Y., Chen Y.T., Wu C.C., Chuang K.H., Lin H.Y., Wang R.S., Chang Y.J., Mendis-Handagama C., Hu L.Q., Lardy H., Chang C.S. Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells. Proc. Natl. Acad. Sci. USA 2006, 103:17718-17723.
111. Zhang M., Xuan S., Bouxsein M.L., von S.D., Akeno N., Faugere M.C., Malluche H., Zhao G., Rosen C.J., Efstratiadis A., Clemens T.L. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J. Biol. Chem. 2002, 277:44005-44012.
112. Zhou X. Roles of androgen receptor in male and female reproduction: lessons from global and cell-specific androgen receptor knockout (ARKO) mice. J. Androl. 2010, 31:235-243.
113. Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat. Rev. Endocrinol. 2009, 5:673-681.