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Where Does Testosterone Come from and How Does It Act?

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Testosterone: From Basic Research to Clinical Applications

Part of the book series: SpringerBriefs in Reproductive Biology ((BRIEFSREPROBIO))

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Abstract

Testosterone has long been considered the “male hormone,” though a deeper examination of the research into this molecule reveals its roles to be far more subtle and complex. In this volume, we provide a brief résumé of the history of testosterone research, from the early pioneers through to the most recent advances in the field. We discover how steroid hormones were first identified, and how testosterone was shown to be essential for male development. Moving forward we explore how and where testosterone is produced, and how the body controls testosterone production. We then investigate the impact testosterone has on different body systems both during their development and function, and how perturbation of testosterone action is associated with disease. We complete our story with an exploration of the emerging roles of testosterone in clinical therapy, and the future potential for manipulation of the testosterone signaling system for human health benefit. Together, these chapters provide an entertaining and informative foray into the secretive world of testosterone.

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References

  • Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EM (2007) Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. J Biol Chem 282:25801–25816

    Google Scholar 

  • Bolton EC, So AY, Chaivorapol C, Haqq CM, Li H, Yamamoto KR (2007) Cell- and gene-specific regulation of primary target genes by the androgen receptor. Genes Dev 21:2005–2017

    Article  PubMed  CAS  Google Scholar 

  • Chadha S, Pache TD, Huikeshoven JM, Brinkmann AO, van der Kwast TH (1994) Androgen receptor expression in human ovarian and uterine tissue of long-term androgen-treated transsexual women. Hum Pathol 25:1198–1204

    Article  PubMed  CAS  Google Scholar 

  • Cheng J, Watkins SC, Walker WH (2007) Testosterone activates mitogen-activated protein kinase via Src kinase and the epidermal growth factor receptor in sertoli cells. Endocrinology 148:2066–2074

    Article  PubMed  CAS  Google Scholar 

  • 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 Endocr 21:895–907

    Article  CAS  Google Scholar 

  • Fix C, Jordan C, Cano P, Walker WH (2004) Testosterone activates mitogen-activated protein kinase and the cAMP response element binding protein transcription factor in Sertoli cells. Proc Nat Acad Sci USA 101:10919–10924

    Article  PubMed  CAS  Google Scholar 

  • Gorczynska E, Handelsman DJ (1995) Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells. Endocrinology 136:2052–2059

    Article  PubMed  CAS  Google Scholar 

  • Heinlein CA, Chang C (2002) The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Mol Endcor 16:2181–2187

    Article  CAS  Google Scholar 

  • Hillier SG (2001) Gonadotropic control of ovarian follicular growth and development. Mol Cell Endocrinol 179:39–46

    Article  PubMed  CAS  Google Scholar 

  • Hillier SG, Tetsuka M, Fraser HM (1997) Location and developmental regulation of androgen receptor in primate ovary. Hum Reprod 12:107–111

    Article  PubMed  CAS  Google Scholar 

  • Hu YC, Wang PH, Yeh S, Wang RS, Xie C, Xu Q, Zhou X, Chao HT, Tsai MY, Chang C (2004) Subfertility and defective folliculogenesis in female mice lacking androgen receptor. Proc Natl Acad Sci USA 101(31):11209–11214

    Google Scholar 

  • Jamnongjit M, Hammes SR (2006) Ovarian steroids: the good, the bad, and the signals that raise them. Cell Cycle 5:1178–1183

    Article  PubMed  CAS  Google Scholar 

  • Jenster G, van der Korput HA, Trapman J, Brinkmann AO (1995) Identification of two transcription activation units in the N-terminal domain of the human androgen receptor. J Biol Chem 270:7341–7346

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, McEwan IJ (2012) Allosteric modulators of steroid hormone receptors: structural dynamics and gene regulation. Endocr Rev 33:271–299

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Betney R, Li J, Thompson EB, McEwan IJ (2004) Induced alpha-helix structure in AF1 of the androgen receptor upon binding transcription factor TFIIF. Biochemistry 43:3008–3013

    Article  PubMed  CAS  Google Scholar 

  • Lavery DN, McEwan IJ (2008) Structural characterization of the native NH2-terminal transactivation domain of the human androgen receptor: a collapsed disordered conformation underlies structural plasticity and protein-induced folding. Biochemistry 47:3360–3369

    Article  PubMed  CAS  Google Scholar 

  • Massie CE, Adryan B, Barbosa-Morais NL, Lynch AG, Tran MG, Neal DE, Mills IG (2007) New androgen receptor genomic targets show an interaction with the ETS1 transcription factor. EMBO Rep 8:871–878

    Article  PubMed  CAS  Google Scholar 

  • McEwan IJ (2004) Molecular mechanisms of androgen receptor-mediated gene regulation: structure-function analysis of the AF-1 domain. Endocr Relat Cancer 11:281–293

    Article  PubMed  CAS  Google Scholar 

  • McEwan IJ (2012) Intrinsic disorder in the androgen receptor: identification, characterisation and drugability. Mol Biosyst 8:82–90

    Article  PubMed  CAS  Google Scholar 

  • Migliaccio A;Castoria G, Di Domenico M, de Falco A, Bilancio A, Lombardi M, Barone MV, Ametrano D, Zannini MS, Abbondanza C, Auricchio F (2000) Steroid-induced androgen receptor-oestradiol receptor beta-Src complex triggers prostate cancer cell proliferation. EMBO J 19:5406–5417

    Google Scholar 

  • Miller WL, Auchus RJ (2011) The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 32:81–151 CVD

    Article  PubMed  CAS  Google Scholar 

  • O’Donnell L, de Kretser DM (2013) Endocrinology of the male reproductive system. http://www.endotext.org/male/male1/male1.html. Accessed 5 June 2013

  • Payne AH, Hardy MP (eds) (2007) The Leydig cell in health and disease. Humana Press, Totowa

    Google Scholar 

  • Pedram A, Razandi M, Sainson RC, Kim JK, Hughes CC, Levin ER (2007) A conserved mechanism for steroid receptor translocation to the plasma membrane. J Biol Chem 282:22278–22288

    Article  PubMed  CAS  Google Scholar 

  • Pi M, Parrill AL, Quarles LD (2010) GPRC6A mediates the non-genomic effects of steroids. J Biol Chem 285:39953–39964

    Article  PubMed  CAS  Google Scholar 

  • Rahman F, Christian HC (2007) Non-classical actions of testosterone: an update. Trends Endocrinol Metab 18:371–378

    Article  PubMed  CAS  Google Scholar 

  • Reid J, Kelly SM, Watt K, Price NC, McEwan IJ (2002) Conformational analysis of the androgen receptor amino-terminal domain involved in transactivation. Influence of structure-stabilizing solutes and protein-protein interactions. J Biol Chem 277:20079–20086

    Article  PubMed  CAS  Google Scholar 

  • Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA (2010) Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol 316:79–85

    Article  PubMed  CAS  Google Scholar 

  • Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HM (2001) Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci USA 98(9):4904–4909

    Google Scholar 

  • Saunders PT, Millar MR, Williams K, Macpherson S, Harkiss D, Anderson RA, Orr B, Groome NP, Scobie G, Fraser HM (2000) Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans. Biol Reprod 63:1098–1105

    Article  PubMed  CAS  Google Scholar 

  • 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 (2006) Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci USA 103(1):224–229

    Google Scholar 

  • Sidiropoulou E, Ghizzoni L, Mastorakos G (2012) Adrenal androgens. http://www.endotext.org/adrenal/adrenal3/adrenal3.htm. Accessed 5 June 2013

  • Simental JA, Sar M, Lane MV, French FS, Wilson EM (1991) Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 266:510–518

    PubMed  CAS  Google Scholar 

  • Skinner MK, Griswold MD (eds) (2005) Sertoli cell biology. Elsevier, Salt Lake City

    Google Scholar 

  • Walters KA, Allan CM, Handelsman DJ (2008) Androgen actions and the ovary. Biol Reprod 78:380–389

    Google Scholar 

  • Wang Q, Li W, Liu XS, Carroll JS, Janne OA, Keeton EK, Chinnaiyan AM, Pienta KJ, Brown M (2007) A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell 27:380–392

    Article  PubMed  Google Scholar 

  • Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, Bondy CA (1998) Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab 83:2479–2485

    Article  PubMed  CAS  Google Scholar 

  • Wilson EM, French FS (1976) Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. J Biol Chem 251:5620–5629

    PubMed  CAS  Google Scholar 

  • 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 U S A 99:13498–13503

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. MRC Centre for Reproductive Health, The Queen’s Medical Research Council, University of Edinburgh, Edinburgh, UK

    Lee B. Smith

  2. School of Medical Sciences, Institute Medical Sciences, University of Aberdeen, Aberdeen, UK

    Iain J. McEwan

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  1. Lee B. Smith
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  2. Iain J. McEwan
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Correspondence to Lee B. Smith .

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Smith, L.B., McEwan, I.J. (2013). Where Does Testosterone Come from and How Does It Act?. In: Testosterone: From Basic Research to Clinical Applications. SpringerBriefs in Reproductive Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8978-8_3

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