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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Several substances such as anabolic androgenic steroids (AAS), peptide hormones like insulin-like growth factor-I (IGF-I), aromatase inhibitors and estrogen antagonists are offered via the Internet, and are assumed without considering the potential deleterious effects that can be caused by their administration. In this study we aimed to determine if nandrolone and stanozolol, two commonly used AAS, could have an effect on Leydig cell tumor proliferation and if their effects could be potentiated by the concomitant use of IGF-I. Using a rat Leydig tumor cell line, R2C cells, as experimental model we found that nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and estradiol (E2) production. When used in combination with IGF-I they were more effective than single molecules in inducing aromatase expression. AAS exhibited estrogenic activity and induced rapid estrogen receptor (ER)-dependent pathways involving IGF1R, AKT, and ERK1/2 phosphorylation. Inhibitors for these kinases decreased AAS-dependent aromatase expression. Up-regulated aromatase levels and related E2 production increased cell proliferation as a consequence of increased cyclin E expression. The observation that ER antagonist ICI182,780 was also able to significantly reduce ASS- and AAS+IGF-induced cell proliferation, confirmed a role for estrogens in AAS-dependent proliferative effects. Taken together these data clearly indicate that the use of high doses of AAS, as it occurs in doping practice, enhances Leydig cell proliferation, increasing the risk of tumor development. This risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS and testicular cancer.

Original languageEnglish (US)
Pages (from-to)2079-2088
Number of pages10
JournalJournal of Cellular Physiology
Volume227
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Stanozolol
Testosterone Congeners
Leydig Cell Tumor
Nandrolone
Insulin-Like Growth Factor I
Tumors
Estrogens
Steroids
Cell Proliferation
Aromatase
Cell proliferation
Estrogen Antagonists
Cyclin E
Aromatase Inhibitors
Phosphorylation
Leydig Cells
Peptide Hormones
Testicular Neoplasms
Tumor Cell Line
Estrogen Receptors

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Nandrolone and stanozolol induce leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system. / Chimento, Adele; Sirianni, Rosa; Zolea, Fabiana; De Luca, Arianna; Lanzino, Marilena; Catalano, Stefania; Andò, Sebastiano; Pezzi, Vincenzo.

In: Journal of Cellular Physiology, Vol. 227, No. 5, 05.2012, p. 2079-2088.

Research output: Contribution to journalArticle

Chimento, A, Sirianni, R, Zolea, F, De Luca, A, Lanzino, M, Catalano, S, Andò, S & Pezzi, V 2012, 'Nandrolone and stanozolol induce leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system', Journal of Cellular Physiology, vol. 227, no. 5, pp. 2079-2088. https://doi.org/10.1002/jcp.22936
Chimento, Adele ; Sirianni, Rosa ; Zolea, Fabiana ; De Luca, Arianna ; Lanzino, Marilena ; Catalano, Stefania ; Andò, Sebastiano ; Pezzi, Vincenzo. / Nandrolone and stanozolol induce leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system. In: Journal of Cellular Physiology. 2012 ; Vol. 227, No. 5. pp. 2079-2088.
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AU - Catalano, Stefania

AU - Andò, Sebastiano

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