Nandrolone and stanozolol induce leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system

Journal of Cellular Physiology

Volumn 227, Issue 5, 2012, Pages 2079-2088

  Chimento, Adele ^a   Sirianni, Rosa ^a   Zolea, Fabiana ^a   De Luca, Arianna ^a   Lanzino, Marilena ^a   Catalano, Stefania ^a   Andò, Sebastiano ^a   Pezzi, Vincenzo ^a  

^a UNIVERSITY OF CALABRIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATASE; CYCLIN E; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NANDROLONE; PROTEIN KINASE B; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; STANOZOLOL;

ANIMAL CELL; ARTICLE; CELL PROLIFERATION; CELL VIABILITY; DRUG EFFECT; ENZYME ACTIVITY; ESTROGEN ACTIVITY; HUMAN; HUMAN CELL; LEYDIG CELL TUMOR; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; SIGNAL TRANSDUCTION; TUMOR CELL; UPREGULATION;

ANABOLIC AGENTS; ANDROGENS; ANIMALS; AROMATASE; AROMATASE INHIBITORS; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN E; ESTROGEN ANTAGONISTS; ESTROGEN RECEPTOR ALPHA; ESTROGENS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HEK293 CELLS; HUMANS; INSULIN-LIKE GROWTH FACTOR I; LEYDIG CELL TUMOR; MALE; NANDROLONE; PROTO-ONCOGENE PROTEINS C-AKT; RATS; RECEPTOR, IGF TYPE 1; STANOZOLOL; TESTICULAR NEOPLASMS;

RATTUS;

EID: 84856187707     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.22936     Document Type: Article

References (49)

1. Al-Ismail K, Torreggiani W, Munk P, Nicolaou S. 2002. Gluteal mass in a bodybuilder: Radiological depiction of a complication of anabolic steroid use. Eur Radiol 12: 1366-1369.
2. Baker J, Hardy MP, Zhou J, Bondy C, Lupu F, Bellve AR, Efstratiadis A. 1996. Effects of an Igf1 gene null mutation on mouse reproduction. Mol Endocrinol 10: 903-918.
3. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW. 2001. Testosterone dose-response relationships in healthy young men. Am J Physiol-Endocrinol Metab 281: E1172-E1181.
4. Bhasin S, Taylor W, Singh R, Artaza J, Sinha-Hikim I, Jasuja R, Choi H, Gonzalez-Cadavid N. 2003. The mechanisms of androgen effects on body composition: Mesenchymal pluripotent cell as the target of androgen action. J Gerontol Ser A Biol Sci Med Sci 58: M1103-M1110.
5. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW. 2005. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 90: 678-688.
6. Bronson FH, Matherne CM. 1997. Exposure to anabolic-androgenic steroids shortens life span of male mice. Med Sci Sports Exerc 29: 615-619.
7. Bunone G, Briand P, Miksicek R, Picard D. 1996. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J 15: 2174-2183.
8. Calfee R, Fadale P. 2006. Popular ergogenic drugs and supplements in young athletes. Pediatrics 117: e577-589.
9. Carreau S, Delalande C, Silandre D, Bourguiba S, Lambard S. 2006. Aromatase and estrogen receptors in male reproduction. Mol Cell Endocrinol 246: 65-68.
10. Casella SJ, Smith EP, van Wyk JJ, Joseph DR, Hynes MA, Hoyt EC, Lund PK. 1987. Isolation of rat testis cDNAs encoding an insulin-like growth factor I precursor. DNA 6: 325-330.
11. Catalano S, Malivindi R, Giordano C, Gu G, Panza S, Bonofiglio D, Lanzino M, Sisci D, Panno ML, Andò S. 2010. Farnesoid X receptor, through the binding with steroidogenic factor 1-responsive element, inhibits aromatase expression in tumor Leydig cells. J Biol Chem 285: 5581-5593.
12. Chimento A, Sirianni R, Delalande C, Silandre D, Bois C, Andò S, Maggiolini M, Carreau S, Pezzi V. 2010. 17β-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ERα. Mol Cell Endocrinol 320: 136-144.
13. Dohle GR, Smit M, Weber RF. 2003. Androgens and male fertility. World J Urol 21: 341-345.
14. Eklöf AC, Thurelius AM, Garle M, Rane A, Sjöqvist F. 2003. The anti-doping hot-line, a means to capture the abuse of doping agents in the Swedish society and a new service function in clinical pharmacology. Eur J Clin Pharmacol 59: 571-577.
15. Evans NA. 1997a. Gym and tonic: A profile of 100 male steroid users. Br J Sport Med 31: 54-58.
16. Evans NA. 1997b. Local complications of self administered anabolic steroid injections. Br J Sport Med 31: 349-350.
17. Faustini-Fustini M, Rochira V, Carani C. 1999. Oestrogen deficiency in men: Where are we today? Eur J Endocr 140: 111-129.
18. Fineschi V, Baroldi G, Monciotti F, Reattelli LP, Turillazzi E. 2001. Anabolic steroid abuse and cardiac sudden death. Arch Pathol Lab Med 125: 253-255.
19. Fineschi V, Riezzo I, Centini F, Silingardi E, Licata M, Beduschi G, Karch S. 2007. Sudden cardiac death during anabolic steroid abuse: Morphologic and toxicologic findings in two fatal cases of bodybuilders. Int J Legal Med 121: 48-53.
20. Foradori CD, Weiser MJ, Handa RJ. 2008. Non-genomic actions of androgens. Front Neuroendocrinol 29: 169-181.
21. Fowler KA, Gill K, Kirma N, Dillehay DL, Tekmal RR. 2000. Overexpression of aromatase leads to development of testicular Leydig cell tumors: An in vivo model for hormone-mediated testicular cancer. Am J Pathol 156: 347-353.
22. Honda SI, Harada N, Ito S, Takagi Y, Maeda S. 1998. Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene. Biochem Biophys Res Commun 252: 445-449.
23. Larsson O, Girnita A, Girnita L. 2005. Role of insulin-like growth factor 1 receptor signalling in cancer. Br J Cancer 92: 2097-2101.
24. Le H, Arnold JT, McFAnn KK, Blackman MR. 2006. DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells. Am J Physiol Endocrinol Metab 290: E952-E960.
25. Lephart ED, Simpson ER. 1991. Assay of aromatase activity. Methods Enzymol 206: 477-483.
26. Li J, Al-Azzawi F. 2009. Mechanism of androgen receptor action. Maturitas 63: 142-148.
27. Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. 1993. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75: 59-72.
28. Ma QL, Yang TL, Yin JY, Peng ZY, Yu M, Liu ZQ, Chen FP. 2009. Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression. Biochem Biophys Res Commun 389: 150-155.
29. Maggiolini M, Donzè O, Jeannin E, Andò S, Picard D. 1999. Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor α. Cancer Res 59(19): 4864-4869.
30. Modlinski R, Fields K. 2006. The effect of anabolic steroids on the gastrointestinal system, kidneys, and adrenal glands. Curr Sports Med Rep 5: 104-109.
31. Pope H, Katz D. 1994. Psychiatric and medical effects of anabolic-androgenic steroid use: A controlled study of 160 athletes. Arch Gen Psychiatry 51: 375-382.
32. Prall OWJ, Sarcevic B, Musgrove EA, Watts CKW, Sutherland RL. 1997. Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J Biol Chem 272: 10882-10894.
33. Prossnitz ER, Maggiolini M. 2009. Mechanisms of estrogen signaling and gene expression via GPR30. Mol Cell Endocrinol 308: 32-38.
34. Robertson KM, O'Donnell L, Simpson ER, Jones MEE. 2002. The Phenotype of the aromatase knockout mouse reveals dietary phytoestrogens impact significantly on testis function. Endocrinology 143: 2913-2921.
35. Rochefort H, Garcia M. 1983. The estrogenic and antiestrogenic activities of androgens in female target tissues. Pharmacol Ther 23: 193-216.
36. Saez JM. 1994. Leydig cells: Endocrine, paracrine, and autocrine regulation. Endocr Rev 15: 574-626.
37. Shahidi NT. 2001. A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin Ther 23: 1355-1390.
38. Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD. 1994. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15: 342-355.
39. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. 2003. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 144: 5081-5088.
40. Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, Bhasin S. 2006. Testosterone inhibits adipogenic differentiation in 3T3-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: 141-154.
41. Sirianni R, Chimento A, Malivindi R, Mazzitelli I, Ando S, Pezzi V. 2007. Insulin-like growth factor-I, regulating aromatase expression through steroidogenic factor 1, supports estrogen-dependent tumor Leydig cell proliferation. Cancer Res 67: 8368-8377.
42. Sirianni R, Chimento A, De Luca A, Zolea F, Carpino A, Rago V, Maggiolini M, Andò S, Pezzi V. 2009. Inhibition of cyclooxygenase-2 down-regulates aromatase activity and decreases proliferation of Leydig tumor cells. J Biol Chem 284: 28905-28916.
43. Socas L, Zumbado M, Pérez-Luzardo O, Ramos A, Pérez C, Hernández JR, Boada LD. 2005. Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: A report of two cases and a review of the literature. Br J Sports Med 39: e27.
44. Song RXD, Fan P, Yue W, Chen Y, Santen RJ. 2006. Role of receptor complexes in the extranuclear actions of estrogen receptor alpha in breast cancer. Endocr Relat Cancer 13: S3-S13.
45. Sylvester PW. 2011. Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. Methods Mol Biol 716: 157-168.
46. Tora L, Mullick A, Metger D, Ponglikitmongkol M, Park I, Chambon P. 1989. The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J 8: 1981-1986.
47. Wakabayashi T, Onda H, Tada T, Iijima M, Itoh Y. 1984. High incidence of peliosis hepatis in autopsy cases of aplastic anemia with special reference to anabolic steroid therapy. Acta Pathol Jpn 34: 1079-1086.
48. Wang GM, O'Shaughnessy PJ, Chubb C, Robaire B, Hardy MP. 2003. Effects of insulin-like growth factor I on steroidogenic enzyme expression levels in mouse Leydig cells. Endocrinology 144: 5058-5064.
49. Zhou J, Bondy C. 1993. Anatomy of the insulin-like growth factor system in the human testis. Fertil Steril 60: 897-904.