Dissociating Behavioral, Autonomic, and Neuroendocrine Effects of Androgen Steroids in Animal Models

  • Amy S. Kohtz
  • Cheryl A. FryeEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 829)


Developments in behavioral assessment, autonomic and/or baseline reactivity, psychopharmacology, and genetics, have contributed significantly to the assessment of performance-enhancing drugs in animal models. Particular classes of steroid hormones: androgenic steroids are of interest. Anecdotally, the performance enhancing effects of androgens are attributed to anabolic events. However, there is a discrepancy between anecdotal evidence and investigative data. While some androgen steroids may promote muscle growth (myogenesis), effects of androgens on performance enhancement are not always seen. Indeed, some effects of androgens on performance may be attributable to their psychological and cardiovascular effects. As such, we consider androgen effects in terms of their behavioral, autonomic, and neuroendocrine components. Techniques are discussed in this chapter, some of which are well established, while others have been more recently developed to study androgen action. Androgens may be considered for their positive impact, negative consequence, or psychotropic properties. Thus, this review aims to elucidate some of the effects and/or mechanisms of androgens on behavioral, autonomic, and/or neuroendocrine assessment that may underlie their controversial performance enhancing effects.

Key words

Androgen Anabolic-steroid Performance enhancement Affect Cognition Myogenesis Animal model 


  1. 1.
    Howell S. and Shalet S., (2001) Testosterone deficiency and replacement. Horm Res. 56, 86–92.Google Scholar
  2. 2.
    Dunger, D. B., Ahmed, M.L., and Ong, K.K. (2006) Early and late weight gain and the timing of puberty. Mol Cell Endocrinol. 254, 140–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Root, A. W. (2002) Bone strength and the adolescent. Adolesc Med. 13, 53–72.PubMedGoogle Scholar
  4. 4.
    Gombos, Z., Hermann, R., Veijola, R., Knip, M., Simell, O., Pollanen, P., and Ilonen, J. (2003) Androgen receptor gene exon 1 CAG repeat polymorphism in Finnish patients with childhood-onset type 1 diabetes. Eur J Endocrinol. 149, 597–600.PubMedCrossRefGoogle Scholar
  5. 5.
    Singh, R., Artaza, J. N., Taylor, W. E., Braga, M., Yuan, X., Gonzalez-Cadavid, N. F., and Bhasin, S. (2006) Testosterone inhibits adipogenic differentiation in 3 T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology. 147, 141–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Sinha-Hikim, I., Taylor, W. E., Gonzalez-Cadavid, N. F., Zheng, W., and Bhasin, S. (2004) Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Enndocrinol Metab. 89, 5245–55.CrossRefGoogle Scholar
  7. 7.
    Marcus, J., Maccoby, E. E., Jacklin, C.N., and Doering, C.H. (1985) Dev Psychobiol. 18, 327–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Geier, D. A., Kern, J. K., and Geier, M. R. (2010) The biological basis of autism spectrum disorders: understanding causation and treatment by clinical geneticists. Acta Neurobiol Exp (Wars) 70, 209–26.Google Scholar
  9. 9.
    Whitehouse, A. J., Maybery, M. T., Hart, R., Mattes, E., Newnham, J. P., Soboda, D. M., Stanley, F. J., and Hickey, M. (2010) Fetal androgen exposure and pragmatic language ability of girls in middle childhood: implications for the extreme male-brain theory of autism. Psychoneuroendocrinology 35, 1259–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Pajer K. Tabbah R., Gardner W., Rubin R. T., Czambel R. K., and Wang Y. (2006) Adrenal androgen and gonadal hormone levels in adolescent girls with conduct disorder. Psychoneuroendocrinology 31, 1245–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Rowe R., Maughan B., Worthman C. M., Costello E. J., and Angold A. (2004) Testosterone, antisocial behavior, and social dominance in boys: pubertal development and biosocial interaction. Biol Psychiatry 55, 546–52.PubMedCrossRefGoogle Scholar
  12. 12.
    van Anders SM, Hamilton LD, and Watson NV. (2007) Multiple partners are associated with higher testosterone in North American men and women. Horm. Behav. 51, 454–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Anderson R. A., Bancroft J., and Wu F. C. (1992) The effects of exogenous testosterone on sexuality and mood of normal men. J Clin Endocrinol Metab. 75, 1503–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Kuepper Y., Alexander N., Osinsky R., Mueller E., Schmitz A., Netter P., and Hennig J. (2010) Aggression – interactions of serotonin and testosterone in healthy men and women. Behav Brain Res. 206, 93–100.PubMedCrossRefGoogle Scholar
  15. 15.
    Sternbach H. (1998) Age-associated testosterone decline in men: clinical issues for psychiatry. Am J Psychiatry. 155, 1310–8.PubMedGoogle Scholar
  16. 16.
    Christiansen K., and Knussmann R. (1987) Sex hormones and cognitive functioning in men. Neuropsychobiology. 18, 27–36.PubMedCrossRefGoogle Scholar
  17. 17.
    Janowsky J. S., Chavez B., and Orwoll E. (2000) Sex steroids modify working memory. J Cogn Neurosci. 12, 407–14.PubMedCrossRefGoogle Scholar
  18. 18.
    Janowsky J. S., Oviatt S. K., and Orwoll E.S. (1994) Testosterone influences spatial cognition in older men. Behav Neurosci. 108, 325–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Wang C., Alexander G., Berman N., Salehian B., Davidson T., McDonald V., Steiner B., Hull L., Callegari C., and Swerdloff R. S. (1996) Testosterone replacement therapy improves mood in hypogonadal men – a clinical research center study. J Clin Endocrinol Metab. 81, 3578–83.PubMedCrossRefGoogle Scholar
  20. 20.
    Alexander G. M., Swerdloff R. S., Wang C., Davidson T., McDonald V., Steiner B., and Hines M. (1997) Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli. Horm Behav. 31, 110–9.Google Scholar
  21. 21.
    Basaria S., and Dobs A.S. (2001) Hypogonadism and androgen replacement therapy in elderly men. Am J Med. 110, 563–72.PubMedCrossRefGoogle Scholar
  22. 22.
    Sloan D. M., and Kornstein S. G. (2003) Gender differences in depression and response to antidepressant treatment. Psychiatr Clin North Am. 26, 581–94.PubMedCrossRefGoogle Scholar
  23. 23.
    Zender R., and Olshansky E. (2009) Women’s mental health: depression and anxiety. Nurs Clin North Am. 44, 355–64.PubMedCrossRefGoogle Scholar
  24. 24.
    Williams C. L., and Meck W. H. (1991) The organizational effects of gonadal steroids on sexually dimorphic spatial ability. Psychoneuroendocrinology 16, 155–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Frick K. M., Burlingame L. A., Arters J. A., and Berger-Sweeney J. (2000) Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex. Neuroscience. 95, 293–307.PubMedCrossRefGoogle Scholar
  26. 26.
    Johnston A. L., and File S. E. (1991) Sex differences in animal tests of anxiety. Physiol Behav. 49, 245–50.PubMedCrossRefGoogle Scholar
  27. 27.
    Kosten T. R., Kosten T. A., McDougle C. J., Hameedi F. A., McCance E. F., Rosen M. I., Oliveto A. H., and Price L. H. (1996) Gender differences in response to intranasal cocaine administration to humans. Biol Psychiatry. 39, 147–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Becker J. B., and Hu M. (2008) Sex differences in drug abuse. Front Neuroendocrinol. 29, 36–47.PubMedCrossRefGoogle Scholar
  29. 29.
    Bitran D., Hilvers R. J., Frye C. A., and Erskine M. S. (1996) Chronic anabolic-androgenic steroid treatment affects brain GABA(A) receptor-gated chloride ion transport. Life Sci. 58, 573–83.PubMedCrossRefGoogle Scholar
  30. 30.
    Bitran D., Kellogg C. K., and Hilvers R. J. (1993) Treatment with an anabolic-androgenic steroid affects anxiety-related behavior and alters the sensitivity of cortical GABAA receptors in the rat. Horm Behav. 27, 568–83.PubMedCrossRefGoogle Scholar
  31. 31.
    Frye C. A., and Lacey E. H. (2001) Posttraining androgens’ enhancement of cognitive performance is temporally distinct from androgens’ increases in affective behavior. Cogn Affect Behav Neurosci. 1, 172–82.PubMedCrossRefGoogle Scholar
  32. 32.
    Frye C. A., Edinger K. L., Lephart E. D., and Walf A. A. (2010) 3alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats. Front Aging Neurosci. 8, 2–5.Google Scholar
  33. 33.
    Walf A. A., and Frye C. A. (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2, 322–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Edinger K. L., and Frye C. A. (2005) Testosterone’s anti-anxiety and analgesic effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus. Psychoneuroendocrinology. 30, 418–30.PubMedCrossRefGoogle Scholar
  35. 35.
    Edinger K. L., and Frye C. A. (2006) Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats. Horm Behav. 50, 216–22.PubMedCrossRefGoogle Scholar
  36. 36.
    Edinger K. L., and Frye C. A. (2007) Androgens’ performance-enhancing effects in the inhibitory avoidance and water maze tasks may involve actions at intracellular androgen receptors in the dorsal hippocampus. Neurobiol Learn Mem. 87, 201–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Frye C. A., Koonce C. J., Edinger K. L., Osborne D. M., and Walf A. A. (2008) Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice. Horm Behav. 54, 726–34.PubMedCrossRefGoogle Scholar
  38. 38.
    Frye C. A., Edinger K., and Sumida K. (2008) Androgen administration to aged male mice increases anti-anxiety behavior and enhances cog­nitive performance. Neuropsychopharmacology. 33, 1049–61.PubMedCrossRefGoogle Scholar
  39. 39.
    Frye C. A., and Edinger K. L. (2004) Testosterone’s metabolism in the hippocampus may mediate its anti-anxiety effects in male rats. Pharmacol Biochem Behav. 78, 473–81.PubMedCrossRefGoogle Scholar
  40. 40.
    Aikey JL, Nyby JG, Anmuth DM, and James PJ. (2002) Testosterone rapidly reduces anxiety in male house mice (Mus musculus). Horm Behav. 42, 448–60.PubMedCrossRefGoogle Scholar
  41. 41.
    Osborne D. M., Edinger K., and Frye C. A. (2009) Chronic administration of androgens with actions at estrogen receptor beta have anti-anxiety and cognitive-enhancing effects in male rats. Age (Dordr). 31, 191–8.CrossRefGoogle Scholar
  42. 42.
    Walf A. A., Paris J. J., and Frye C. A. (2009) Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance. Psychoneuroendocrinology. 34, 909–16.PubMedCrossRefGoogle Scholar
  43. 43.
    Buddenberg T. E., Komorowski M., Ruocco L. A., Silva M. A., and Topic B. (2009) Attenuating effects of testosterone on depressive-like behavior in the forced swim test in healthy male rats. Brain Res Bull. 79, 182–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Frye C. A., and Sturgis J. D. (1995) Neurosteroids affect spatial/reference, working, and long-term memory of female rats. Neurobiol Learn Mem. 64, 83–96.PubMedCrossRefGoogle Scholar
  45. 45.
    Boyle G. J., Neumann D. L., Furedy J. J., and Westbury H. R. (2010) Sex differences in verbal and visual-spatial tasks under different hemispheric visual-field presentation conditions. Percept Mot Skills. 110, 396–410.PubMedCrossRefGoogle Scholar
  46. 46.
    Leggett V., Jacobs P., Nation K., Scerif G., and Bishop D. V. (2010) Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review. Dev Med Child Neurol. 52, 119–29.PubMedCrossRefGoogle Scholar
  47. 47.
    Frye C. A., and Seliga A. M. (2001) Testosterone increases analgesia, anxiolysis, and cognitive performance of male rats. Cogn Affect Behav Neurosci. 1, 371–81.PubMedCrossRefGoogle Scholar
  48. 48.
    Kritzer M. F., and Pugach I. (2001) Administration of tamoxifen but not flutamide to hormonally intact, adult male rats mimics the effects of short-term gonadectomy on the catecholamine innervation of the cerebral cortex. J Comp Neurol. 431, 444–59.PubMedCrossRefGoogle Scholar
  49. 49.
    Benice T. S., and Raber J. (2009) Dihydrotestosterone modulates spatial working-memory performance in male mice. J Neurochem. 110, 902–11.PubMedCrossRefGoogle Scholar
  50. 50.
    Edinger K. L., and Frye C. A. (2004) Testosterone’s analgesic, anxiolytic, and cognitive-enhancing effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus. Behav Neurosci. 118, 1352–64.PubMedCrossRefGoogle Scholar
  51. 51.
    Edinger K. L., Lee B., and Frye C. A. (2004) Mnemonic effects of testosterone and its 5alpha-reduced metabolites in the conditioned fear and inhibitory avoidance tasks. Pharmacol Biochem Behav. 78, 559–68.PubMedCrossRefGoogle Scholar
  52. 52.
    Frye C. A., Edinger K. L., Seliga A. M., and Wawrzycki J. M. (2004) 5alpha-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats. Psychoneuroendocrinology. 29, 1019–27.PubMedCrossRefGoogle Scholar
  53. 53.
    Frye C. A., and McCormick C. M. (2000) The neurosteroid, 3alpha-androstanediol, prevents inhibitory avoidance deficits and pyknotic cells in the granule layer of the dentate gyrus induced by adrenalectomy in rats. Brain Res. 855, 166–70.PubMedCrossRefGoogle Scholar
  54. 54.
    Frye C. A., Park D., Tanaka M., Rosellini R., and Svare B. (2001) The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. Psychoneuroendocrinology. 26, 731–50.PubMedCrossRefGoogle Scholar
  55. 55.
    Frye C. A., Rhodes M. E., Rosellini R., Svare B. (2002) The nucleus accumbens as a site of action for rewarding properties of testosterone and its 5alpha-reduced metabolites. Pharmacol Biochem Behav. 74, 119–27.PubMedCrossRefGoogle Scholar
  56. 56.
    Pike C. J., Carroll J. C., Rosario E. R., Barron A. M. (2009) Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol. 30, 239–58.PubMedCrossRefGoogle Scholar
  57. 57.
    Rosario E.R., Chang L., Head E.H., Stanczyk F.Z., Pike C.J. (2011) Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease. Neurobiol Aging. 32, 604–613.Google Scholar
  58. 58.
    Nguyen TV, Jayaraman A, Quaglino A, Pike CJ. (2010) Androgens selectively protect against apoptosis in hippocampal neurones. J Neuroendocrinol. 22, 1013–22.PubMedCrossRefGoogle Scholar
  59. 59.
    Raber J. (2008) AR, apoE, and cognitive function. Horm Behav. 53, 706–15.PubMedCrossRefGoogle Scholar
  60. 60.
    Frye C. A., Sturgis J. D. (1995) Neurosteroids affect spatial/reference, working, and long-term memory of female rats. Neurobiol Learn Mem. 64, 83–96.PubMedCrossRefGoogle Scholar
  61. 61.
    Kanit, L., Taskiran, D., Yilmaz, O. A., Balkan, B., Demirgoren, S., Furedy, J. J., and Pogun, S. (2000) Sexually dimorphic cognitive styles in rats emerges after puberty. Brain Res Bull. 52, 243–248.PubMedCrossRefGoogle Scholar
  62. 62.
    Frye C. A., Duffy C. K., and Walf A. A. (2007) Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task. Neurobiol Learn Mem. 88, 208–16.PubMedCrossRefGoogle Scholar
  63. 63.
    Paris J. J., and Frye C. A. (2008) Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks. Reproduction. 136, 105–15.PubMedCrossRefGoogle Scholar
  64. 64.
    Walf A. A., Sumida K., and Frye C. A. (2006) Inhibiting 5alpha-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats. Psychopharma­cology (Berl). 186, 302–11.CrossRefGoogle Scholar
  65. 65.
    Bahrke M. S., Yesalis C. E., and Brower K. J. (1998) Anabolic-androgenic steroid abuse and performance-enhancing drugs among adolescents. Child Adolesc Psychiatr Clin N Am. 7, 821–38.PubMedGoogle Scholar
  66. 66.
    Yesalis C. E., Barsukiewicz C. K., Kopstein A. N., and Bahrke M. S. (1997) Trends in anabolic-androgenic steroid use among adolescents. Arch Pediatr Adolesc Med 151, 1197–206.PubMedCrossRefGoogle Scholar
  67. 67.
    Svare B., Mann M., Broida J., Kinsley C., Ghiraldi L., Miele J., and Konen C. (1983) Intermale aggression and infanticide in aged C57BL/6J male mice: behavioral deficits are not related to serum testosterone (T) levels and are not recovered by supplemental T. Neurobiol Aging. 4, 305–12.PubMedCrossRefGoogle Scholar
  68. 68.
    Kinsley C., and Svare B. (1988) Prenatal stress alters maternal aggression in mice. Physiol Behav. 42, 7–13.PubMedCrossRefGoogle Scholar
  69. 69.
    Frye C. A., Van Keuren K. R., and Erskine M. S. (1996) Behavioral effects of 3 alpha-androstanediol. I: Modulation of sexual receptivity and promotion of GABA-stimulated chloride flux. Behav Brain Res. 79, 109–18.Google Scholar
  70. 70.
    Archer J. (1991) The influence of testosterone on human aggression. Br J Psychol. 82, 1–28.PubMedCrossRefGoogle Scholar
  71. 71.
    Meaney M. J., and McEwen B. S. (1986) Testosterone implants into the amygdala during the neonatal period masculinize the social play of juvenile female rats. Brain Res. 398, 324–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Rhees R. W., Kirk B. A., Sephton S., and Lephart E. D. Effects of prenatal testosterone on sexual behavior, reproductive morphology and LH secretion in the female rat. Dev Neurosci. 19, 430–7Google Scholar
  73. 73.
    Su T. P., Pagliaro M., Schmidt P. J., Pickar D., Wolkowitz O., and Rubinow D. R. (1993) Neuropsychiatric effects of anabolic steroids in male normal volunteers. JAMA. 269, 2760–4.PubMedCrossRefGoogle Scholar
  74. 74.
    Choi P. Y., and Pope H. G. Jr. (1994) Violence toward women and illicit androgenic-anabolic steroid use. Ann Clin Psychiatry. 6, 21–5.PubMedCrossRefGoogle Scholar
  75. 75.
    Greenblatt R. B., and Karpas A. (1983) Hormone therapy for sexual dysfunction. The only “true aphrodisiac”. Postgrad Med. 74, 88–80, 84–9.Google Scholar
  76. 76.
    Bahrke M. S., Yesalis C. E. 3rd, and Wright J. E. (1990) Psychological and behavioural effects of endogenous testosterone levels and anabolic-androgenic steroids among males. Sports Med. 10, 303–37.PubMedCrossRefGoogle Scholar
  77. 77.
    Bahrke M. S., Yesalis C. E. 3rd, Wright J. E. (1996) Psychological and behavioural effects of endogenous testosterone and anabolic-androgenic steroids. An update. Sports Med. 22, 367–90.Google Scholar
  78. 78.
    Pope H. G. Jr, and Katz D. L. (1994) Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes. Arch Gen Psychiatry. 51, 375–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Moss H. B., Panzak G. L., and Tarter R. E. (1993) Sexual functioning of male anabolic steroid abusers. Arch Sex Behav. 22, 1–12.PubMedCrossRefGoogle Scholar
  80. 80.
    Miczek K. A., Haney M., Tidey J., Vatne T., Weerts E., and DeBold J. F. (1989) Temporal and sequential patterns of agonistic behavior: effects of alcohol, anxiolytics and psychomotor stimulants. Psychopharmacology (Berl). 97, 149–51.CrossRefGoogle Scholar
  81. 81.
    Moyer K. E. (1968) Kinds of aggression and their physiological basis. Commun. Behav. Bio. 2, 65–87.Google Scholar
  82. 82.
    Edwards D. A. (1969). Early androgen stimulation and aggressive behavior in male and female mice. Physiology & Behavior, 4, 333–338.CrossRefGoogle Scholar
  83. 83.
    Miczek K. A., DeBold J. F., and Thompson M. L. (1984) Pharmacological, hormonal, and behavioral manipulations in analysis of aggressive behavior. Prog Clin Biol Res 167, 1–26.PubMedGoogle Scholar
  84. 84.
    Kubala K. H., McGinnis M. Y., Anderson G. M., and Lumia A. R. (2008) The effects of an anabolic androgenic steroid and low serotonin on social and non-social behaviors in male rats. Brain Res. 26, 21–9.CrossRefGoogle Scholar
  85. 85.
    Albert D. J., Jonik R. H., and Walsh M. L. (1993) Influence of combined estradiol and testosterone implants on the aggressiveness of nonaggressive female rats. Physiol Behav. 53, 709–13.PubMedCrossRefGoogle Scholar
  86. 86.
    Rezek D. L., and Whalen R. E. Male rat brain androgen metabolism and sexual behavior. Neuroendocrinology. 25, 141–9.Google Scholar
  87. 87.
    Morali G., Oropeza M. V., Lemus A. E., and Perez-Palacios G. (1994) Mechanisms regulating male sexual behavior in the rat: role of 3 alpha- and 3 beta-androstanediols. Biol Reprod. 51, 562–71.PubMedCrossRefGoogle Scholar
  88. 88.
    Parrott R. F. (1974) The effects of various androgens on peripheral structures in the castrated male rat. J Reprod Fertil. 38, 49–57.PubMedCrossRefGoogle Scholar
  89. 89.
    Howland B. E. (1975) The influence of feed restriction and subsequent re-feeding on gonadotrophin secretion and serum testosterone levels in male rats. J Reprod Fertil. 44, 429–36PubMedCrossRefGoogle Scholar
  90. 90.
    Asarian L., and Geary N. Modulation of appetite by gonadal steroid hormones. Philos Trans R Soc Lond B Biol Sci. 361, 1251–63.Google Scholar
  91. 91.
    Allan C. A., and McLachlan R. I. (2010) Androgens and obesity. Curr Opin Endocrinol Diabetes Obes.17, 224–32.Google Scholar
  92. 92.
    Gentry R. T., and Wade G. N. (1976) Androgenic control of food intake and body weight in male rats. J Comp Physiol Psychol. 90, 18–25.PubMedCrossRefGoogle Scholar
  93. 93.
    Elias A. N., and Wilson A. F. (1993) Exercise and gonadal function. Hum Reprod. 8, 1747–61.Google Scholar
  94. 94.
    Campbell B. C., Dreber A., Apicella C. L., Eisenberg D. T., Gray P. B., Little A. C., Garcia J. R., Zamore R. S., and Lum J. K. (2010) Testosterone exposure, dopaminergic reward, and sensation-seeking in young men. Physiol Behav. 99, 451–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Rosellini R. A., Svare B. B., Rhodes M. E., and Frye C. A. (2001) The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. Brain Res Brain Res Rev. 37, 162–71.PubMedCrossRefGoogle Scholar
  96. 96.
    Frye C. A. (2007) Some rewarding effects of androgens may be mediated by actions of its 5alpha-reduced metabolite 3alpha-androstanediol. Pharmacol Biochem Behav. 86, 354–67.PubMedCrossRefGoogle Scholar
  97. 97.
    Fuxjager M. J., Forbes-Lorman R. M., Coss D. J., Auger C. J., Auger A. P., and Marler C. A. (2010) Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression. Proc Natl Acad Sci U S A. 107, 12393–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Robinson D. L., Phillips P. E., Budygin E. A., Trafton B. J., Garris P. A., and Wightman R. M. (2001) Sub-second changes in accumbal dopamine during sexual behavior in male rats. Neuroreport. 12, 49–52.CrossRefGoogle Scholar
  99. 99.
    Robinson T. E., Gorny G., Mitton E., and Kolb B. (2001) Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex. Synapse. 39, 257–66.PubMedCrossRefGoogle Scholar
  100. 100.
    Wood R. I. (2004) Reinforcing aspects of androgens. Physiol Behav. 83, 279–89.PubMedGoogle Scholar
  101. 101.
    Triemstra J. L., Sato S. M., Wood R. I. (2008) Testosterone and nucleus accumbens dopamine in the male Syrian hamster. Psychoneuroendocrinology. 33, 386–94.PubMedCrossRefGoogle Scholar
  102. 102.
    Kashkin K. B., and Kleber H. D. (1989) Hooked on hormones? An anabolic steroid addiction hypothesis. JAMA. 262, 3166–70.PubMedCrossRefGoogle Scholar
  103. 103.
    Wright J. E. (1980) Anabolic steroids and athletics. Exerc Sport Sci Rev. 8, 149–202.PubMedCrossRefGoogle Scholar
  104. 104.
    Bonson K. R., Johnson R. G., Fiorella D., Rabin R. A., Winter J. C. (1994) Serotonergic control of androgen-induced dominance. Pharmacol Biochem Behav. 49, 313–22.PubMedCrossRefGoogle Scholar
  105. 105.
    Russo S. J., Sun W. L., Minerley A. C., Weierstall K., Nazarian A., Festa E. D., Niyomchai T., Akhavan A., Jenab S., and Quiñones-Jenab V. (2010) Progesterone does not affect cocaine-induced conditioned place preference or locomotor activity in male rats. Ethn Dis. 20, 73–7.Google Scholar
  106. 106.
    Kohtz A. S., Paris J. J., and Frye C. A. (2010) Low doses of cocaine decrease, and high doses increase, anxiety-like behavior and brain progestogen levels among intact rats. Horm Behav. 57, 474–80.PubMedCrossRefGoogle Scholar
  107. 107.
    Takahashi A., Kwa C., Debold J. F., and Miczek K. A. (2010) GABA(A) receptors in the dorsal raphé nucleus of mice: escalation of aggression after alcohol consumption. Psychopharmacology (Berl). 211, 467–77.CrossRefGoogle Scholar
  108. 108.
    de Almeida R. M., Ferrari P. F., Parmigiani S., and Miczek K. A. (2005) Escalated aggressive behavior: dopamine, serotonin and GABA. Eur J Pharmacol. 526, 51–64.PubMedCrossRefGoogle Scholar
  109. 109.
    Haupt H. A., and Rovere G. D. (1984) Anabolic steroids: a review of the literature. Am J Sports Med. 12, 469–84.PubMedCrossRefGoogle Scholar
  110. 110.
    Grokett B. H., Ahmad N., and Warren D. W. (1992) The effects of an anabolic steroid (oxandrolone) on reproductive development in the male rat. Acta Endocrinol (Copenh). 126, 173–8.Google Scholar
  111. 111.
    Helfman T., and Falanga V. (1995) Stanozolol as a novel therapeutic agent in dermatology. J Am Acad Dermatol. 33, 254–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Hansell D. T., Davies J. W., Shenkin A., Garden O. J., Burns H. J., and Carter D. C. (1989) The effects of an anabolic steroid and peripherally administered intravenous nutrition in the early postoperative period. JPEN J Parenter Enteral Nutr. 13, 349–58.PubMedCrossRefGoogle Scholar
  113. 113.
    Johnson L. C., and O’Shea J. P. (1969) Anabolic steroid: effects on strength development. Science. 164, 957–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Earnest C. P., Olson M. A., Broeder C. E., Breuel K. F., and Beckham S. G. (2000) In vivo 4-androstene-3,17-dione and 4-androstene-3 beta,17 beta-diol supplementation in young men. Eur J Appl Physiol. 81, 229–32.PubMedCrossRefGoogle Scholar
  115. 115.
    Brown G. A., Vukovich M., and King D. S. (2006) Testosterone prohormone supplements. Med Sci Sports Exerc. 38, 1451–61.PubMedCrossRefGoogle Scholar
  116. 116.
    Jasuja R., Ramaraj P., Mac R. P., Singh A. B., Storer T. W., Artaza J., Miller A., Singh R., Taylor W. E., Lee M. L., Davidson T., Sinha-Hikim I., Gonzalez-Cadavid N., and Bhasin S. (2005) Delta-4-androstene-3,17-dione binds androgen receptor, promotes myogenesis in vitro, and increases serum testosterone levels, fat-free mass, and muscle strength in hypogonadal men. J Clin Endocrinol Metab. 90, 855–63.PubMedCrossRefGoogle Scholar
  117. 117.
    Yue P., Chatterjee K., Beale C., Poole-Wilson P. A., and Collins P. (1995) Testosterone relaxes rabbit coronary arteries and aorta. Circulation. 91, 1154–60.PubMedGoogle Scholar
  118. 118.
    Costarella C. E., Stallone J. N., Rutecki G. W., and Whittier F. C. (1996) Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther. 277, 34–9.PubMedGoogle Scholar
  119. 119.
    Chou T. M., Sudhir K., Hutchison S. J., Ko E., Amidon T. M., Collins P., and Chatterjee K. (1996) Testosterone induced dilation of canine coronary conductance and resistance arteries in vivo. Circulation. 94, 2614–2619.Google Scholar
  120. 120.
    Schrör K., Morinelli T. A., Masuda A., Matsuda K., Mathur R. S., and Halushka P. V. (1994) Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs. Eur J Clin Invest. 1, 50–2.Google Scholar
  121. 121.
    Hydock D. S., Lien C. Y., Schneider C. M., and Hayward R. (2007) Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats. Am J Physiol Heart Circ Physiol. 293, 3254–64.CrossRefGoogle Scholar
  122. 122.
    Hassan N. A., Salem M. F., and Sayed M. A. (2009) Doping and effects of anabolic androgenic steroids on the heart: histological, ultrastructural, and echocardiographic assessment in strength athletes. Hum Exp Toxicol. 28, 273–83.PubMedCrossRefGoogle Scholar
  123. 123.
    Goldstein D. R., Dobbs T., Krull B., and Plumb V. J. (1998) Clenbuterol and anabolic steroids: a previously unreported cause of myocardial infarction with normal coronary arteriograms. South Med J. 91, 780–4.PubMedCrossRefGoogle Scholar
  124. 124.
    Nestler J. E., Barlascini C. O., Clore J. N., and Blackard W. G. (1988) Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab. 66, 57–61.PubMedCrossRefGoogle Scholar
  125. 125.
    Fowler N. O., McCall D., Chou T. C., Holmes J. C., and Hanenson I. B. (2004) Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Am J Cardiol. 37, 223–30.CrossRefGoogle Scholar
  126. 126.
    Du J., Zhang L., and Wang Z. (2009) Testosterone inhibits the activity of peroxisome proliferator-activated receptor gamma in a transcriptional transaction assay. Pharmazie. 64, 692–3.PubMedGoogle Scholar
  127. 127.
    Hansmann G., and Zamanian R. T. (2009) PPARgamma activation: a potential treatment for pulmonary hypertension. Sci Transl Med. 1, 12–14.CrossRefGoogle Scholar
  128. 128.
    Fruchart J. C., Duriez P., and Staels B. (1999) Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol. 10, 245–57.Google Scholar
  129. 129.
    Buchan K. W., and Hassall D. G. (2000) PPAR agonists as direct modulators of the vessel wall in cardiovascular disease. Med Res Rev. 20, 350–66.PubMedCrossRefGoogle Scholar
  130. 130.
    Ketsawatsomkron P., Pelham C. J., Groh S., Keen H. L., Faraci F. M., and Sigmund C. D. (2010) Does peroxisome proliferator-activated receptor-gamma (PPAR gamma) protect from hypertension directly through effects in the vasculature? J Biol Chem. 285, 9311–6.PubMedCrossRefGoogle Scholar
  131. 131.
    Wu J. S., Lin T. N., and Wu K. K. (2009) Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins. J Cell Physiol. 220, 58–71.PubMedCrossRefGoogle Scholar
  132. 132.
    Wu J., Chen L., Zhang D., Huo M., Zhang X., Pu D., and Guan Y. (2009) Peroxisome proliferator-activated receptors and renal diseases. Front Biosci. 14, 995–1009.PubMedCrossRefGoogle Scholar
  133. 133.
    Wu J. S., Cheung W. M., Tsai Y. S., Chen Y. T., Fong W. H., Tsai H. D., Chen Y. C., Liou J. Y., Shyue S. K., Chen J. J., Chen Y. E., Maeda N., Wu K. K., and Lin T. N. (2009) Ligand-activated peroxisome proliferator-activated receptor-gamma protects against ischemic cerebral infarction and neuronal apoptosis by 14-3-3 epsilon upregulation. Circulation. 119, 1124–34.PubMedCrossRefGoogle Scholar
  134. 134.
    Minutoli L., Antonuccio P., Polito F., Bitto A., Squadrito F., Irrera N., Nicotina P. A., Fazzari C., Montalto A. S., Di Stefano V., Romeo C., Altavilla D. (2009) Peroxisome proliferator activated receptor beta/delta activation prevents extracellular regulated kinase 1/2 phosphorylation and protects the testis from ischemia and reperfusion injury. J Urol. 181, 1913–21.PubMedCrossRefGoogle Scholar
  135. 135.
    Jones R. D., Pugh P. J., Hall J., Channer K. S., and Jones T. H. (2003) Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse. Eur J Endocrinol. 148, 111–20.PubMedCrossRefGoogle Scholar
  136. 136.
    Dimicco J. A., and Zaretsky D. V. (2007) The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol Regul Integr Comp Physiol. 292, R47–63.PubMedCrossRefGoogle Scholar
  137. 137.
    Shekhar A., Johnson P. L., Sajdyk T. J., Fitz S. D., Keim S. R., Kelley P. E., Gehlert D. R., and DiMicco J. A. (2006) Angiotensin-II is a putative neurotransmitter in lactate-induced panic-like responses in rats with disruption of GABAergic inhibition in the dorsomedial hypothalamus. J Neurosci. 26, 9205–15.PubMedCrossRefGoogle Scholar
  138. 138.
    Traish A. M., Feeley R. J., and Guay A. (2009) Mechanisms of obesity and related pathologies: androgen deficiency and endothelial dysfunction may be the link between obesity and erectile dysfunction. FEBS J. 276, 5755–67.PubMedCrossRefGoogle Scholar
  139. 139.
    Traish A. M., Saad F., and Guay A. (2009) The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 30, 23–32.PubMedCrossRefGoogle Scholar
  140. 140.
    Traish A. M., Guay A., Feeley R., and Saad F. (2009) The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl. 30, 10–22.Google Scholar
  141. 141.
    Claessens F., Denayer S., Van Tilborgh N., Kerkhofs S., Helsen C., and Haelens A. (2008) Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl Recept Signal. 6, 008.Google Scholar
  142. 142.
    Shaknovich R., Shue G., and Kohtz D. S. (1992) Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84). Mol Cell Biol. 12, 5059–68.PubMedGoogle Scholar
  143. 143.
    Zoubeidi A., Zardan A., Beraldi E., Fazli L., Sowery R., Rennie P., Nelson C., and Gleave M. (2007) Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Res. 67, 10455–65.PubMedCrossRefGoogle Scholar
  144. 144.
    Shaffer P. L., Jivan A., Dollins D. E., Claessens F., and Gewirth D. T. (2004) Structural basis of androgen receptor binding to selective androgen response elements. Proc Natl Acad Sci U S A. 101, 4758–63.PubMedCrossRefGoogle Scholar
  145. 145.
    Knudsen K. E., Cavenee W. K., and Arden K. C. (1999) D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability. Cancer Res. 59, 2297–301.PubMedGoogle Scholar
  146. 146.
    Petre-Draviam C. E., Cook S. L., Burd C. J., Marshall T. W., Wetherill Y. B., and Knudsen K. E. (2003) Specificity of cyclin D1 for androgen receptor regulation. Cancer Res. 63, 4903–13.PubMedGoogle Scholar
  147. 147.
    Urbanucci A., Waltering K. K., Suikki H. E., Helenius M. A., and Visakorpi T. (2008) Androgen regulation of the androgen receptor coregulators. BMC Cancer. 8, 219.PubMedCrossRefGoogle Scholar
  148. 148.
    Karvonen U., Jänne O. A., and Palvimo J. J. (2006) Androgen receptor regulates nuclear trafficking and nuclear domain residency of corepressor HDAC7 in a ligand-dependent fashion. Exp Cell Res. 312, 3165–83.PubMedCrossRefGoogle Scholar
  149. 149.
    Björkman M., Iljin K., Halonen P., Sara H., Kaivanto E., Nees M., and Kallioniemi O. P. (2008) Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG-positive prostate cancer. Int J Cancer. 123, 2774–81.PubMedCrossRefGoogle Scholar
  150. 150.
    Welsbie D. S., Xu J., Chen Y., Borsu L., Scher H. I., Rosen N., and Sawyers C. L. (2009) Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer. Cancer Res. 69, 958–66.PubMedCrossRefGoogle Scholar
  151. 151.
    Baulieu E. E., Atger M., Best-Belpomme M., Corvol P., Courvalin J. C., Mester J., Milgrom E., Robel P., Rochefort H., and De Catalogne D. (1975) Steroid hormone receptors. Vitam Horm. 33, 649–736.Google Scholar
  152. 152.
    Sato S. M., Johansen J. A., Jordan C. L., and Wood R. I. (2010) Membrane androgen receptors may mediate androgen reinforcement. Psychoneuroendocrinology. 35, 1063–73.PubMedCrossRefGoogle Scholar
  153. 153.
    Farnsworth W. E. (1990) The prostate plasma membrane as an androgen receptor. Membr Biochem. 9, 141–62.PubMedCrossRefGoogle Scholar
  154. 154.
    Bottino M. C., and Lanari C. (2010) Extra nuclear localization of steroid receptors and non genomic activation mechanisms. Medicina (B Aires). 70, 173–84.Google Scholar
  155. 155.
    MacLusky N. J., Clark C. R., Shanabrough M., and Naftolin F. (1987) Metabolism and binding of androgens in the spinal cord of the rat. Brain Res. 422, 83–91.PubMedCrossRefGoogle Scholar
  156. 156.
    García-Ovejero D., Veiga S., García-Segura L. M., and Doncarlos L. L. (2002) Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol. 450, 256–71.PubMedCrossRefGoogle Scholar
  157. 157.
    DonCarlos L. L., Sarkey S., Lorenz B., Azcoitia I., Garcia-Ovejero D., Huppenbauer C., and Garcia-Segura L. M. (2006) Novel cellular phenotypes and subcellular sites for androgen action in the forebrain. Neuroscience. 138, 801–7.PubMedCrossRefGoogle Scholar
  158. 158.
    DonCarlos L. L., Garcia-Ovejero D., Sarkey S., Garcia-Segura L. M., and Azcoitia I. (2003) Androgen receptor immunoreactivity in forebrain axons and dendrites in the rat. Endocrinology. 144, 3632–8.PubMedCrossRefGoogle Scholar
  159. 159.
    Jänne O. A., Palvimo J. J., Kallio P., and Mehto M. (1993) Androgen receptor and mechanism of androgen action. Ann Med. 25, 83–9.PubMedCrossRefGoogle Scholar
  160. 160.
    Doherty P. C., and Sheridan P. J. (1981) Uptake and retention of androgen in neurons of the brain of the golden hamster. Brain Res. 219, 327–34.PubMedCrossRefGoogle Scholar
  161. 161.
    Sar M., and Stumpf W. E. (1972) Cellular localization of androgen in the brain and pituitary after the injection of tritiated testosterone. Experientia. 28, 1364–6.PubMedCrossRefGoogle Scholar
  162. 162.
    Sar M., and Stumpf W. E. (1973) Autoradiographic localization of radioactivity in the rat brain after the injection of 1,2-3 H-testosterone. Endocrinology. 92, 251–6.PubMedCrossRefGoogle Scholar
  163. 163.
    Sar M., and Stumpf W. E. (1981) Combined autoradiography and immunohistochemistry for simultaneous localization of radioactively labeled steroid hormones and antibodies in the brain. J Histochem Cytochem. 29, 161–6.PubMedCrossRefGoogle Scholar
  164. 164.
    Kritzer M. F. (1997) Selective colocalization of immunoreactivity for intracellular gonadal hormone receptors and tyrosine hydroxylase in the ventral tegmental area, substantia nigra, and retrorubral fields in the rat. J Comp Neurol. 379, 247–60.PubMedCrossRefGoogle Scholar
  165. 165.
    Lieberburg I., Maclusky N. J., and McEwen B. S. (1977) 5alpha-Dihydrotestosterone (DHT) receptors in rat brain and pituitary cell nuclei. Endocrinology. 100, 598–607.PubMedCrossRefGoogle Scholar
  166. 166.
    Hajszan T., MacLusky N. J., and Leranth C. (2008) Role of androgens and the androgen receptor in remodeling of spine synapses in limbic brain areas. Horm Behav. 53, 638–46.PubMedCrossRefGoogle Scholar
  167. 167.
    Clark R. L., Antonello J. M., Grossman S. J., Wise L. D., Anderson C., Bagdon W. J., Prahalada S., MacDonald J. S., and Robertson R. T. (1990) External genitalia abnormalities in male rats exposed in utero to finasteride, a 5 alpha-reductase inhibitor. Teratology. 42, 91–100.PubMedCrossRefGoogle Scholar
  168. 168.
    di Salle E., Giudici D., Briatico G., Ornati G., and Panzeri A. (1993) Hormonal effects of turosteride, a 5 alpha-reductase inhibitor, in the rat. J Steroid Biochem Mol Biol. 46, 549–55.PubMedCrossRefGoogle Scholar
  169. 169.
    Reismann P., Likó I., Igaz P., Patócs A., and Rácz K. (2009) Pharmacological options for treatment of hyperandrogenic disorders. Mini Rev Med Chem. 9, 1113–26.PubMedCrossRefGoogle Scholar
  170. 170.
    Garcia Valencia V., Sanchez M., Gutierrez M., Cantabrana B., and Hidalgo A. (1991) Effects of steroidal and non-steroidal antiandrogens on the left atrium of the rat in vitro. Gen Pharmacol. 22, 1081–6.CrossRefGoogle Scholar
  171. 171.
    Imperato-McGinley J., Sanchez R. S., Spencer J. R., Yee B., and Vaughan E. D. (1992) Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies. Endocrinology. 131, 1149–56.PubMedCrossRefGoogle Scholar
  172. 172.
    Raudrant D., and Rabe T. (2003) Progestogens with antiandrogenic properties. Drugs. 63, 463–92.PubMedCrossRefGoogle Scholar
  173. 173.
    Azuma K., Nakashiro K., Sasaki T., Goda H., Onodera J., Tanji N., Yokoyama M., and Hamakawa H. (2010) Anti-tumor effect of small interfering RNA targeting the androgen receptor in human androgen-independent prostate cancer cells. Biochem Biophys Res Commun. 391, 1075–9.PubMedCrossRefGoogle Scholar
  174. 174.
    Fimmel S., Kurfurst R., Bonté F., and Zouboulis C. C. (2007) Responsiveness to androgens and effectiveness of antisense oligonucleotides against the androgen receptor on human epidermal keratinocytes is dependent on the age of the donor and the location of cell origin. Horm Metab Res. 39, 157–65.PubMedCrossRefGoogle Scholar
  175. 175.
    Yeh S., Tsai M. Y., Xu Q., Mu X. M., Lardy H., Huang K. E., Lin H., Yeh S. D., Altuwaijri S., Zhou X., Xing L., Boyce B. F., Hung M. C., Zhang S., Gan L., and 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, 13498–503.PubMedCrossRefGoogle Scholar
  176. 176.
    Zhou X. (2010) Roles of androgen receptor in male and female reproduction: lessons from global and cell-specific androgen receptor knockout (ARKO) mice. J Androl. 31, 235–43.PubMedCrossRefGoogle Scholar
  177. 177.
    Handa R. J., Pak T. R., Kudwa A. E., Lund T. D., and Hinds L. (2008) An alternate pathway for androgen regulation of brain function: activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5alpha-androstane-3beta,17beta-diol. Horm Behav. 53, 741–52.PubMedCrossRefGoogle Scholar
  178. 178.
    Alejandre-Gomez M., Garcia-Segura L. M., and Gonzalez-Burgos I. (2007) Administration of an inhibitor of estrogen biosynthesis facilitates working memory acquisition in male rats. Neurosci Res. 58, 272–7.PubMedCrossRefGoogle Scholar
  179. 179.
    Ellem S. J., and Risbridger G. P. (2010) Aromatase and regulating the estrogen:androgen ratio in the prostate gland. J Steroid Biochem Mol Biol. 118, 246–51.PubMedCrossRefGoogle Scholar
  180. 180.
    Lephart E. D., Lund T. D., and Horvath T. L. (2001) Brain androgen and progesterone metabolizing enzymes: biosynthesis, distribution and function. Brain Res Brain Res Rev. 37, 25–37.PubMedCrossRefGoogle Scholar
  181. 181.
    Séralini G., and Moslemi S. (2001) Aromatase inhibitors: past, present and future. Mol Cell Endocrinol. 178, 117–31.PubMedCrossRefGoogle Scholar
  182. 182.
    Reddy D. S., and Jian K. (2010) The testosterone-derived neurosteroid androstanediol is a positive allosteric modulator of GABAA receptors. J Pharmacol Exp Ther. 334, 1031–41.PubMedCrossRefGoogle Scholar
  183. 183.
    Pak T. R., Chung W. C., Lund T. D., Hinds L. R., Clay C. M., and Handa R. J. (2005) The androgen metabolite, 5alpha-androstane-3beta, 17beta-diol, is a potent modulator of estrogen receptor-beta1-mediated gene transcription in neuronal cells. Endocrinology. 146, 147–55.PubMedCrossRefGoogle Scholar
  184. 184.
    Alderson L. M., and Baum M. J. (1981) Differential effects of gonadal steroids on dopamine metabolism in mesolimbic and nigro-striatal pathways of male rat brain. Brain Res. 218, 189–206.PubMedCrossRefGoogle Scholar
  185. 185.
    Goudsmit E., Feenstra M. G., and Swaab D. F. (1990) Central monoamine metabolism in the male Brown-Norway rat in relation to aging and testosterone. Brain Res Bull. 25, 755–63.PubMedCrossRefGoogle Scholar
  186. 186.
    Jalilian-Tehrani M. H., Karakiulakis G., Le Blond C. B., Powell R., and Thomas P. J. (1982) Androgen-induced sexual dimorphism in high affinity dopamine binding in the brain transcends the hypothalamic-limbic region. Br J Pharmacol. 75, 37–48.PubMedGoogle Scholar
  187. 187.
    Mitchell J. B., and Stewart J. (1989) Effects of castration, steroid replacement, and sexual experience on mesolimbic dopamine and sexual behaviors in the male rat. Brain Res. 491, 116–27.PubMedCrossRefGoogle Scholar
  188. 188.
    Moore W. V. (1988) Anabolic steroid use in adolescence. JAMA. 260, 3484–6.PubMedCrossRefGoogle Scholar
  189. 189.
    Cunningham G. R., Tindall D. J., and Means A. R. (1979) Differences in steroid specificity for rat androgen binding protein and the cytoplasmic receptor. Steroids. 33, 261–76.PubMedCrossRefGoogle Scholar
  190. 190.
    Verhoeven G., Heyns W., and De Moor P. (1975) Testosterone receptors in the prostate and other tissues. Vitam Horm. 33, 265–81.PubMedCrossRefGoogle Scholar
  191. 191.
    DiMeo A. N., and Wood R. I. (2006) Self-administration of estrogen and dihydrotestosterone in male hamsters. Horm Behav. 49, 519–26.PubMedCrossRefGoogle Scholar
  192. 192.
    Sheridan P. J. (1984) Autoradiographic localization of steroid receptors in the brain. Clin Neuropharmacol. 7, 281–95.PubMedCrossRefGoogle Scholar
  193. 193.
    Sato S. M., Johansen J. A., Jordan C. L., and Wood R. I. (2010) Membrane androgen receptors may mediate androgen reinforcement. Psychoneuroendocrinology. 35, 1063–73.PubMedCrossRefGoogle Scholar
  194. 194.
    Erskine M. S. (1983) Effects of an anti-androgen and 5 alpha-reductase inhibitors on estrus duration in the cycling female rat. Physiol Behav. 30(4), 519–24.PubMedCrossRefGoogle Scholar
  195. 195.
    Majewska M. D., Harrison N. L., Schwartz R. D., Barker J. L., and Paul S. M. (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 232, 1004–7.PubMedCrossRefGoogle Scholar
  196. 196.
    Im W. B., Blakeman D. P., Davis J. P., and Ayer D. E. (1990) Studies on the mechanism of interactions between anesthetic steroids and gamma-aminobutyric acidA receptors. Mol Pharmacol. 37, 429–34.PubMedGoogle Scholar
  197. 197.
    Masonis A. E., and McCarthy M. P. (1995) Direct effects of the anabolic/androgenic steroids, stanozolol and 17 alpha-methyltestosterone, on benzodiazepine binding to the gamma-aminobutyric acid(a) receptor. Neurosci Lett. 189, 35–8.PubMedCrossRefGoogle Scholar
  198. 198.
    Gee K. W. (1988) Steroid modulation of the GABA/benzodiazepine receptor-linked chloride ionophore. Mol Neurobiol. 2, 291–317.PubMedCrossRefGoogle Scholar
  199. 199.
    Penatti C. A., Davis M. C., Porter D. M., and Henderson L. P. (2010) Altered GABAA receptor-mediated synaptic transmission disrupts the firing of gonadotropin-releasing hormone neurons in male mice under conditions that mimic steroid abuse. J Neurosci. 30, 6497–506.PubMedCrossRefGoogle Scholar
  200. 200.
    Clark A. S., Costine B. A., Jones B. L., Kelton-Rehkopf M. C., Meerts S. H., Nutbrown-Greene L. L., Penatti C. A., Porter D. M., Yang P., and Henderson L. P. (2006) Sex- and age-specific effects of anabolic androgenic steroids on reproductive behaviors and on GABAergic transmission in neuroendocrine control regions. Brain Res. 1126, 122–38.PubMedCrossRefGoogle Scholar
  201. 201.
    Carroll M. E., Lynch W. J., Roth M. E., Morgan A. D., and Cosgrove K. P. (2004) Sex and estrogen influence drug abuse. Trends Pharmacol Sci. 25, 273–9.PubMedCrossRefGoogle Scholar
  202. 202.
    Kuiper G. G., Lemmen J. G., Carlsson B., Corton J. C., Safe S. H., van der Saag P. T., van der Burg B., and Gustafsson J. A. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 139, 4252–63.PubMedCrossRefGoogle Scholar
  203. 203.
    Tremblay G. B., Tremblay A., Copeland N. G., Gilbert D. J., Jenkins N. A., Labrie F., and Giguère V. (1997) Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol. 11, 353–65.PubMedCrossRefGoogle Scholar
  204. 204.
    Basu A., and Rowan B. G. (2005) Genes related to estrogen action in reproduction and breast cancer. Front Biosci. 10, 2346–72.PubMedCrossRefGoogle Scholar
  205. 205.
    Connor E. E., Wood D. L., Sonstegard T. S., da Mota A. F., Bennett G. L., Williams J. L., and Capuco A. V. (2005) Chromosomal mapping and quantitative analysis of estrogen-related receptor alpha-1, estrogen receptors alpha and beta and progesterone receptor in the bovine mammary gland. J Endocrinol. 185, 593–603.PubMedCrossRefGoogle Scholar
  206. 206.
    Hewitt S. C., and Korach K. S. (2003) Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues. Reproduction. 125, 143–9.PubMedCrossRefGoogle Scholar
  207. 207.
    Shimizu T., Kamegai J., Tamura H., Ishii S., Sugihara H., and Oikawa S. (2005) The estrogen receptor (ER) alpha, but not ER beta, gene is expressed in hypothalamic growth hormone-releasing hormone neurons of the adult female rat. Neurosci Res. 52, 121–5.PubMedCrossRefGoogle Scholar
  208. 208.
    Walf A. A., Rhodes M. E., and Frye C. A. (2004) Antidepressant effects of ERbeta-selective estrogen receptor modulators in the forced swim test. Pharmacol Biochem Behav. 78, 523–9.PubMedCrossRefGoogle Scholar
  209. 209.
    Rissman E. F., Heck A. L., Leonard J. E., Shupnik M. A., and Gustafsson J. A. (2002) Disruption of estrogen receptor beta gene impairs spatial learning in female mice. Proc Natl Acad Sci U S A. 99, 3996–4001.PubMedCrossRefGoogle Scholar
  210. 210.
    Walf A. A., Ciriza I., Garcia-Segura L. M., and Frye C. A. (2008) Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate estradiol’s modulation of affective and sexual behavior, respectively. Neuropsychopharmacology. 33, 431–40.PubMedCrossRefGoogle Scholar
  211. 211.
    Graham-Lorence S., Amarneh B., White R. E., Peterson J. A., and Simpson E. R. (1995) A three-dimensional model of aromatase cytochrome P450. Protein Sci. 4, 1065–80.PubMedCrossRefGoogle Scholar
  212. 212.
    Küppers E. and Beyer C. (1998) Expression of aromatase in the embryonic and postnatal mouse striatum. Brain Res Mol Brain Res. 63, 184–8.PubMedCrossRefGoogle Scholar
  213. 213.
    Connolly P. B., Roselli C. E., and Resko J. A. (1990) Aromatase activity in adult guinea pig brain is androgen dependent. Biol Reprod. 43, 698–703.PubMedCrossRefGoogle Scholar
  214. 214.
    McEwen B. S. (1980) Gonadal steroids: humoral modulators of nerve-cell function. Mol Cell Endocrinol. 18, 151–64.PubMedCrossRefGoogle Scholar
  215. 215.
    Jänne O. A. (1990) Androgen interaction through multiple steroid receptors. NIDA Res Monogr. 102, 178–86.PubMedGoogle Scholar
  216. 216.
    Reel J. R., Humphrey R. R., Shih Y. H., Windsor B. L., Sakowski R., Creger P. L., and Edgren R. A. (1979) Competitive progesterone antagonists: receptor binding and biologic activity of testosterone and 19-nortestosterone derivatives. Fertil Steril. 31, 552–61.PubMedGoogle Scholar
  217. 217.
    Ip M. M., Milholland R. J., Kim U., and Rosen F. (1982) Androgen control of cytosol progesterone receptor levels in the MT-W9B transplantable mammary tumor in the rat. J Natl Cancer Inst. 69, 673–81.PubMedGoogle Scholar
  218. 218.
    Markiewicz L., and Gurpide E. (1997) Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays. Methods Find Exp Clin Pharmacol. 19, 215–22.PubMedGoogle Scholar
  219. 219.
    González-Montelongo M. C., Marín R., and Gómez T, Díaz M. (2010) Androgens are powerful non-genomic inducers of calcium sensitization in visceral smooth muscle. Steroids. 75, 533–8.Google Scholar
  220. 220.
    Patrão M. T., Silva E. J., and Avellar M. C. (2009) Androgens and the male reproductive tract: an overview of classical roles and current perspectives. Arq Bras Endocrinol Metabol. 53, 934–45.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of PsychologyThe University at Albany-SUNYAlbanyUSA
  2. 2.Departments of Psychology and Biological Sciences, Centers for Life Sciences and Neuroscience ResearchThe University at Albany-SUNYAlbanyUSA

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