Table of Contents
ISRN Endocrinology
Volume 2011 (2011), Article ID 839149, 7 pages
http://dx.doi.org/10.5402/2011/839149
Review Article

Testosterone, Endothelial Health, and Erectile Function

1Institute for Molecular and Cell Biology of the University of Porto (IBMC-UP), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
2Department of Biochemistry (U38-FCT), Faculty of Medicine of the University of Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal
3Department of Urology, Hospital de S. João, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal
4Department of Experimental Biology, Faculty of Medicine of the University of Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal

Received 2 June 2011; Accepted 7 July 2011

Academic Editors: C. Anderwald and W. B. Chan

Copyright © 2011 Angela Castela et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. M. B. Goldstein, J. P. Meehan, J. W. Morrow, P. A. Buckley, and F. A. Rogers, “The fibrous skeleton of the corpora cavernosa and its probable function in the mechanism of erection,” British Journal of Urology, vol. 57, no. 5, pp. 574–578, 1985. View at Google Scholar
  2. T. J. Bivalacqua, M. F. Usta, H. C. Champion, P. J. Kadowitz, and W. J. G. Hellstrom, “Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease,” Journal of Andrology, vol. 24, no. 6, supplement, pp. S17–S37, 2003. View at Google Scholar · View at Scopus
  3. H. Porst and I. D. Sharlip, “Anatomy and physiology of erection,” in Standard Practice in Sexual Medicine, H. Porst and J. Buvat, Eds., pp. 31–42, Blackwell Publishing, 2006. View at Google Scholar
  4. A. L. Burnett, C. J. Lowenstein, D. S. Bredt, T. S. K. Chang, and S. H. Snyder, “Nitric oxide: a physiologic mediator of penile erection,” Science, vol. 257, no. 5068, pp. 401–403, 1992. View at Google Scholar · View at Scopus
  5. P. Hedlund, A. Aszódi, A. Pfeifer et al., “Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 5, pp. 2349–2354, 2000. View at Publisher · View at Google Scholar
  6. K. E. Andersson, “Pharmacology of penile erection,” Pharmacological Reviews, vol. 53, no. 3, pp. 417–450, 2001. View at Google Scholar · View at Scopus
  7. K. J. Hurt, B. Musicki, M. A. Palese et al., “Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 6, pp. 4061–4066, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. H. Padma-Nathan, G. Christ, G. Adaikan et al., “Pharmacotherapy for erectile dysfunction,” Journal of Sexual Medicine, vol. 1, no. 2, pp. 128–140, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. M. B. Siroky, K. M. Azadzoi, R. Kloner et al., “Vasculogenic erectile dysfunction: newer therapeutic strategies,” Journal of Urology, vol. 170, no. 2, pp. S24–S30, 2003. View at Google Scholar · View at Scopus
  10. I. Sáenz de Tejada, J. Angulo, S. Cellek et al., “Pathophysiology of erectile dysfunction,” Journal of Sexual Medicine, vol. 2, no. 1, pp. 26–39, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. D. Behrendt and P. Ganz, “Endothelial function: from vascular biology to clinical applications,” American Journal of Cardiology, vol. 90, no. 10, pp. 40L–48L, 2002. View at Google Scholar · View at Scopus
  12. C. Vlachopoulos, K. Rokkas, N. Ioakeimidis, and C. Stefanadis, “Inflammation, metabolic syndrome, erectile dysfunction, and coronary artery disease: common links,” European Urology, vol. 52, no. 6, pp. 1590–1600, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Kirby, G. Jackson, and U. Simonsen, “Endothelial dysfunction links erectile dysfunction to heart disease,” International Journal of Clinical Practice, vol. 59, no. 2, pp. 225–229, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. M. M. Hartge, U. Kintscher, and T. Unger, “Endothelial dysfunction and its role in diabetic vascular disease,” Endocrinology and Metabolism Clinics of North America, vol. 35, no. 3, pp. 551–560, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. A. M. J. Wassink, J. K. Olijhoek, and F. L. J. Visseren, “The metabolic syndrome: metabolic changes with vascular consequences,” European Journal of Clinical Investigation, vol. 37, no. 1, pp. 8–17, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Costa and R. Virag, “The endothelial-erectile dysfunction connection: an essential update,” Journal of Sexual Medicine, vol. 6, no. 9, pp. 2390–2404, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Folkman and Y. Shing, “Angiogenesis,” The Journal of Biological Chemistry, vol. 267, no. 16, pp. 10931–10934, 1992. View at Google Scholar · View at Scopus
  18. C. B. Hunting, W. A. Noort, and J. J. Zwaginga, “Circulating endothelial (progenitor) cells reflect the state of the endothelium: vascular injury, repair and neovascularization,” Vox Sanguinis, vol. 88, no. 1, pp. 1–9, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Dimmeler and A. M. Zeiher, “Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis?” Journal of Molecular Medicine, vol. 82, no. 10, pp. 671–677, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. T. Asahara, H. Masuda, T. Takahashi et al., “Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization,” Circulation Research, vol. 85, no. 3, pp. 221–228, 1999. View at Google Scholar · View at Scopus
  21. C. Costa, “Role of endothelial progenitor cells in the metabolic syndrome,” in Oxidative Stress, Inflammation and Angiogenesis in the Metabolic Syndrome, Soares and Costa, Eds., vol. 6, pp. 101–121, Springer, Berlin, Germany, 2009. View at Google Scholar
  22. E. Miller-Kasprzak and P. P. Jagodziński, “Endothelial progenitor cells as a new agent contributing to vascular repair,” Archivum Immunologiae et Therapiae Experimentalis, vol. 55, no. 4, pp. 247–259, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. C. Foresta, L. De Toni, A. Di Mambro, A. Garolla, A. Ferlin, and D. Zuccarello, “The PDE5 inhibitor sildenafil increases circulating endothelial progenitor cells and CXCR4 expression,” Journal of Sexual Medicine, vol. 6, no. 2, pp. 369–372, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Baumhäkel, N. Werner, M. Böhm, and G. Nickenig, “Circulating endothelial progenitor cells correlate with erectile function in patients with coronary heart disease,” European Heart Journal, vol. 27, no. 18, pp. 2184–2188, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. C. Foresta, N. Caretta, A. Lana, A. Cabrelle, G. Palù, and A. Ferlin, “Circulating endothelial progenitor cells in subjects with erectile dysfunction,” International Journal of Impotence Research, vol. 17, no. 3, pp. 288–290, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. American Society of Andrology, “Testosterone replacement therapy for male aging: SAS position statement,” Journal of Andrology, vol. 27, no. 2, pp. 133–134, 2006. View at Google Scholar
  27. A. A. Yassin and F. Saad, “Testosterone and erectile dysfunction,” Journal of Andrology, vol. 29, no. 6, pp. 593–604, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Wald, R. B. Meacham, L. S. Ross, and C. S. Niederberger, “Testosterone replacement therapy for older men,” Journal of Andrology, vol. 27, no. 2, pp. 126–132, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. C. A. Allan and R. I. McLachlan, “Age-related changes in testosterone and the role of replacement therapy in older men,” Clinical Endocrinology, vol. 60, no. 6, pp. 653–670, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. T. H. Jones, “Testosterone associations with erectile dysfunction, diabetes, and the metabolic syndrome,” European Urology, Supplements, vol. 6, no. 16, pp. 847–857, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Aversa, R. Bruzziches, D. Francomano, M. Natali, P. Gareri, and G. Spera, “Endothelial dysfunction and erectile dysfunction in the aging man: review article,” International Journal of Urology, vol. 17, no. 1, pp. 38–47, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Akishita, M. Hashimoto, Y. Ohike et al., “Low testosterone level is an independent determinant of endothelial dysfunction in men,” Hypertension Research, vol. 30, no. 11, pp. 1029–1034, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Hougaku, J. L. Fleg, S. S. Najjar et al., “Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements,” American Journal of Physiology, vol. 290, no. 2, pp. E234–E242, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. N. Makhsida, J. Shah, G. Yan, H. Fisch, and R. Shabsigh, “Hypogonadism and metabolic syndrome: implications for testosterone therapy,” Journal of Urology, vol. 174, no. 3, pp. 827–834, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. A. M. Traish, F. Saad, and A. Guay, “The dark side of testosterone deficiency: II. type 2 diabetes and insulin resistance,” Journal of Andrology, vol. 30, no. 1, pp. 23–32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. R. K. Stellato, H. A. Feldman, O. Hamdy, E. S. Horton, and J. B. Mckinlay, “Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts Male Aging Study,” Diabetes Care, vol. 23, no. 4, pp. 490–494, 2000. View at Google Scholar · View at Scopus
  37. M. A. Boyanov, Z. Boneva, and V. G. Christov, “Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency,” Aging Male, vol. 6, no. 1, pp. 1–7, 2003. View at Google Scholar · View at Scopus
  38. D. Kapoor, E. Goodwin, K. S. Channer, and T. H. Jones, “Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes,” European Journal of Endocrinology, vol. 154, no. 6, pp. 899–906, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. P. Mårin, M. Krotkiewski, and P. Björntorp, “Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues,” The European Journal of Medicine, vol. 1, no. 6, pp. 329–336, 1992. View at Google Scholar · View at Scopus
  40. P. Marin, S. Holmäng, L. Jönsson et al., “The effects of testosterone treatment on body composition and metabolism in middle-aged obese men,” International Journal of Obesity and Related Metabolic Disorders, vol. 16, no. 12, pp. 991–997, 1992. View at Google Scholar · View at Scopus
  41. F. Saad, L. Gooren, A. Haider, and A. Yassin, “Effects of testosterone gel followed by parenteral testosterone undecanoate on sexual dysfunction and on features of the metabolic syndrome,” Andrologia, vol. 40, no. 1, pp. 44–48, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Saad, L. J. Gooren, A. Haider, and A. Yassin, “A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate,” Journal of Andrology, vol. 29, no. 1, pp. 102–105, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. A. A. Yassin, F. Saad, and A. Traish, “Testosterone undecanoate restores erectile function in a subset of patients with venous leakage: a series of case reports,” Journal of Sexual Medicine, vol. 3, no. 4, pp. 727–735, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. D. Kurbatov, J. Kuznetsky, and A. Traish, “Testosterone improves erectile function in hypogonadal patients with venous leakage,” Journal of Andrology, vol. 29, no. 6, pp. 630–637, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. D. Schultheiss, R. Badalyan, A. Pilatz et al., “Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results,” World Journal of Urology, vol. 21, no. 5, pp. 320–324, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. C. A. Heinlein and C. Chang, “The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions,” Molecular Endocrinology, vol. 16, no. 10, pp. 2181–2187, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. L. Lu, L. Kuang, H. Zhu et al., “Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5α-reductase inhibitor,” Asian Journal of Andrology, vol. 9, no. 6, pp. 843–847, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Yamamoto, S. Sasaki, H. Tatsura et al., “Penile apoptosis in association with p53 under lack of testosterone,” Urological Research, vol. 32, no. 1, pp. 9–13, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Shabsigh, J. F. Raymond, C. A. Olsson, K. Otoole, and R. Buttyan, “Androgen induction of DNA synthesis in the rat penis,” Urology, vol. 52, no. 4, pp. 723–728, 1998. View at Publisher · View at Google Scholar · View at Scopus
  50. V. Mirone, C. Imbimbo, F. Fusco, P. Verze, M. Creta, and G. Tajana, “Androgens and morphologic remodeling at penile and cardiovascular levels: a common piece in complicated puzzles?” European Urology, vol. 56, no. 2, pp. 309–316, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. A. M. Traish, “Androgens play a pivotal role in maintaining penile tissue architecture and erection: a review,” Journal of Andrology, vol. 30, no. 4, pp. 363–369, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. A. M. Traish, I. Goldstein, and N. N. Kim, “Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction,” European Urology, vol. 52, no. 1, pp. 54–70, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Schirar, C. Bonnefond, C. Meusnier, and E. Devinoy, “Androgens modulate nitric oxide synthase messenger ribonucleic acid expression in neurons of the major pelvic ganglion in the rat,” Endocrinology, vol. 138, no. 8, pp. 3093–3102, 1997. View at Publisher · View at Google Scholar · View at Scopus
  54. D. F. Penson, C. Ng, L. Cai, J. Rajfer, and N. F. González-Cadavid, “Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat,” Biology of Reproduction, vol. 55, no. 3, pp. 567–574, 1996. View at Google Scholar · View at Scopus
  55. J. A. Lugg, J. Rajfer, and N. F. Gonzalez-Cadavid, “Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat,” Endocrinology, vol. 136, no. 4, pp. 1495–1501, 1995. View at Google Scholar · View at Scopus
  56. C. M. Reilly, P. Zamorano, V. S. Stopper, and T. M. Mills, “Androgenic regulation of NO availability in rat penile erection,” Journal of Andrology, vol. 18, no. 2, pp. 110–115, 1997. View at Google Scholar · View at Scopus
  57. A. Morelli, S. Filippi, R. Mancina et al., “Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa,” Endocrinology, vol. 145, no. 5, pp. 2253–2263, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. A. M. Traish, K. Park, V. Dhir, N. N. Kim, R. B. Moreland, and I. Goldstein, “Effects of castration and androgen replacement on erectile function in a rabbit model,” Endocrinology, vol. 140, no. 4, pp. 1861–1868, 1999. View at Google Scholar · View at Scopus
  59. X. H. Zhang, A. Morelli, M. Luconi et al., “Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum,” European Urology, vol. 47, no. 3, pp. 409–416, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Buvat and A. Lemaire, “Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy,” Journal of Urology, vol. 158, no. 5, pp. 1764–1767, 1997. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Morales, B. Johnston, J. P. W. Heaton, and M. Lundie, “Testosterone supplementation for hypogonadal impotence: assessment of biochemical measures and therapeutic outcomes,” Journal of Urology, vol. 157, no. 3, pp. 849–854, 1997. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Jain, A. W. Rademaker, and K. T. Mcvary, “Testosterone supplementation for erectile dysfunction: results of a meta-analysis,” Journal of Urology, vol. 164, no. 2, pp. 371–375, 2000. View at Google Scholar · View at Scopus
  63. S. Y. Kalinchenko, G. I. Kozlov, N. P. Gontcharov, and G. V. Katsiya, “Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone,” Aging Male, vol. 6, no. 2, pp. 94–99, 2003. View at Google Scholar · View at Scopus
  64. A. Aversa, A. M. Isidori, G. Spera, A. Lenzi, and A. Fabbri, “Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction,” Clinical Endocrinology, vol. 58, no. 5, pp. 632–638, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. R. Shabsigh, J. M. Kaufman, C. Steidle, and H. Padma-Nathan, “Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone,” Journal of Urology, vol. 172, no. 2, pp. 658–663, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. T. J. Bivalacqua, B. Musicki, M. F. Usta et al., “Endothelial nitric oxide synthase gene therapy for erectile dysfunction,” Current Pharmaceutical Design, vol. 11, no. 31, pp. 4059–4067, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. T. J. Bivalacqua, M. F. Usta, H. C. Champion, P. J. Kadowitz, and W. J. G. Hellstrom, “Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease,” Journal of Andrology, vol. 24, no. 6, pp. S17–S37, 2003. View at Google Scholar · View at Scopus
  68. R. B. Moreland, “Pathophysiology of erectile dysfunction: the contributions of trabecular structure to function and the role of functional antagonism,” International Journal of Impotence Research, vol. 12, no. 4, supplement, pp. S39–S46, 2000. View at Google Scholar · View at Scopus
  69. B. Musicki and A. L. Burnett, “Endothelial dysfunction in diabetic erectile dysfunction,” International Journal of Impotence Research, vol. 19, no. 2, pp. 129–138, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. Y. Takuwa, “Endothelin in vascular and endocrine systems: biological activities and its mechanisms of action,” Endocrine Journal, vol. 40, no. 5, pp. 489–506, 1993. View at Google Scholar · View at Scopus
  71. A. Garncarczyk, M. Jurzak, and K. Gojniczek, “Characteristic of the endogenous peptides–endothelins and their role in the connective tissue fibrosis,” Wiadomości lekarskie, vol. 61, no. 4–6, pp. 126–134, 2008. View at Google Scholar · View at Scopus
  72. P. Kumanov, A. Tomova, and G. Kirilov, “Testosterone replacement therapy in male hypogonadism is not associated with increase of endothelin-1 levels,” International Journal of Andrology, vol. 30, no. 1, pp. 41–47, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. J. K. Ryu, J. Y. Han, Y. C. Chu et al., “Expression of cavernous transforming growth factor-β1 and its Type II Receptor in patients with erectile dysfunction,” International Journal of Andrology, vol. 27, no. 1, pp. 42–49, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. S. M. Haag, E. W. Hauck, C. Szardening-Kirchner et al., “Alterations in the transforming growth factor (TGF)-β pathway as a potential factor in the pathogenesis of peyronie's disease,” European Urology, vol. 51, no. 1, pp. 255–261, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Gelman, H. Garbán, R. Shen et al., “Transforming growth factor-β1 (TGF-β1) in penile and prostate growth in the rat during sexual maturation,” Journal of Andrology, vol. 19, no. 1, pp. 50–57, 1998. View at Google Scholar · View at Scopus
  76. G. D. Norata, G. Tibolla, P. M. Seccomandi, A. Poletti, and A. L. Catapano, “Dihydrotestosterone decreases tumor necrosis factor-α and lipopolysaccharide-induced inflammatory response in human endothelial cells,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 2, pp. 546–554, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. X. Zhang, L. Wang, Y. Dou et al., “Testosterone and estradiol modulate TNF-α-induced expression of adhesion molecules in endothelial cells,” Methods and Findings in Experimental and Clinical Pharmacology, vol. 24, no. 3, pp. 125–130, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. A. M. Traish, R. Munarriz, L. O'Connell et al., “Effects of medical or surgical castration on erectile function in an animal model,” Journal of Andrology, vol. 24, no. 3, pp. 381–387, 2003. View at Google Scholar · View at Scopus
  79. A. M. Traish and A. T. Guay, “Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence,” Journal of Sexual Medicine, vol. 3, no. 3, pp. 382–407, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Traish and N. Kim, “The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function,” Journal of Sexual Medicine, vol. 2, no. 6, pp. 759–770, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. R. S. Rogers, T. M. Graziottin, C. M. Lin, Y. W. Kan, and T. F. Lue, “Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats,” International Journal of Impotence Research, vol. 15, no. 1, pp. 26–37, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. A. M. Traish, P. Toselli, S. J. Jeong, and N. N. Kim, “Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency,” Journal of Andrology, vol. 26, no. 2, pp. 242–248, 2005. View at Google Scholar · View at Scopus
  83. O. Yildiz and M. Seyrek, “Vasodilating mechanisms of testosterone,” Experimental and Clinical Endocrinology and Diabetes, vol. 115, no. 1, pp. 1–6, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. Z. J. Shen, X. L. Zhou, Y. L. Lu, and Z. D. Chen, “Effect of androgen deprivation on penile ultrastructure,” Asian Journal of Andrology, vol. 5, no. 1, pp. 33–36, 2003. View at Google Scholar · View at Scopus
  85. A. Armagan, K. Hatsushi, and P. Toselli, “The effects of testosterone deficiency on the structural integrity of the penile dorsal nerve in the rat,” International Journal of Impotence Research, vol. 20, no. 1, pp. 73–78, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. K. Baba, M. Yajima, S. Carrier et al., “Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve,” Urology, vol. 56, no. 3, pp. 533–538, 2000. View at Publisher · View at Google Scholar · View at Scopus
  87. K. Baba, M. Yajima, S. Carrier et al., “Delayed testosterone replacement restores nitric oxide synthase-containing nerve fibres and the erectile response in rat penis,” British Journal of Urology International, vol. 85, no. 7, pp. 953–958, 2000. View at Publisher · View at Google Scholar
  88. C. Foresta, N. Caretta, A. Lana et al., “Reduced number of circulating endothelial progenitor cells in hypogonadal men,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 11, pp. 4599–4602, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. C. Foresta, D. Zuccarello, L. De Toni, A. Garolla, N. Caretta, and A. Ferlin, “Androgens stimulate endothelial progenitor cells through an androgen receptor-mediated pathway,” Clinical Endocrinology, vol. 68, no. 2, pp. 284–289, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Mantalaris, N. Panoskaltsis, Y. Sakai et al., “Localization of androgen receptor expression in human bone marrow,” Journal of Pathology, vol. 193, no. 3, pp. 361–366, 2001. View at Publisher · View at Google Scholar · View at Scopus
  91. E. O. Abu, A. Horner, V. Kusec, J. T. Triffitt, and J. E. Compston, “The localization of androgen receptors in human bone,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 10, pp. 3493–3497, 1997. View at Publisher · View at Google Scholar · View at Scopus