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Cited by 71Hormonal and reproductive studiesPharmacological Effects and AssaysDoping in Sports

Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review

Open access
Salerno, Monica, Cascio, Orazio, Bertozzi, Giuseppe, Sessa, Francesco, Messina, Antonietta, Monda, Vincenzo, Cipolloni, Luigi, Biondi, Antonio +2 more·2018·Oncotarget
DOI 10.18632/oncotarget.24767PMC PMC5922407
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Abstract

// Monica Salerno 1 , Orazio Cascio 2 , Giuseppe Bertozzi 1 , Francesco Sessa 1 , Antonietta Messina 3 , Vincenzo Monda 3 , Luigi Cipolloni 4 , Antonio Biondi 5 , Aurora Daniele 6 and Cristoforo Pomara 2 1 University of Foggia, Department of Clinical and Experimental Medicine, Foggia, Italy 2 University of Catania, Department of Medical, Surgical and Advanced Technologies, “G.F. Ingrassia”, Catania, Italy 3 University of Campania “L. Vanvitelli”, Department of Experimental Medicine, Naples, Italy 4 Università degli Studi di Roma “La Sapienza”, Department of Public Health, Roma, Italy 5 University of Catania, Department of Surgery, Catania, Italy 6 University of Campania “L. Vanvitelli”, CEINGE Biotecnologie Avanzate S.C. a r.l., Naples, Italy Correspondence to: Cristoforo Pomara, email: cristoforo.pomara@unict.it Keywords: abuse; anabolic-androgenic steroids (AAS); carcinogenicity; insulin-like growth factor 1 (IGF-1); molecular mechanisms Received: December 29, 2017 Accepted: February 27, 2018 Published: April 10, 2018 ABSTRACT Anabolic androgenic steroids (AAS) are some of the most common drugs used among athletes, frequently in combination with resistance training, to improve physical performance or for aesthetic purpose. A great number of scientific reports showed the detrimental effects of anabolic androgenic steroids on different organs and tissues. In this literature review, we analyzed the AAS-mediated carcinogenicity, focusing on Leydig cell tumor. AAS-induced carcinogenicity can affect DNA transcription through two pathways. It can act directly via the androgen receptor, by means of dihydrotestosterone (DHT) produced by the action of 5-a-reductase. It can also work through the estrogen receptor, by means of estradiol produced by CYP19 aromatase. In addition, nandrolone and stanazolol can activate the PI3K/AKT and PLC/PKC pathways via IGF-1 . This would result in cell proliferation in Leydig cell cancer, or magnify cyclin D1 concentration inducing breast cell proliferation. AAS abuse is becoming a serious public health concern in view of the severe health consequences secondary to AAS abuse. The negative role of AAS in supraphysiological dosage impairs the expression of enzymes involved in testosterone biosynthesis. Abnormal synthesis of testosterone plays has a negative effect on the hormonal changes/regulation, and might be involved in certain carcinogenic mechanisms. At the light of this review, it could become very interesting to perform an information campaign more strengthened in gyms and schools in order to prevent male fertility impairment and other tissues damage.

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  • Numerous studies have documented oncogenic properties of male steroid hormones and their derivatives on several human organs, including testis, liver, breast, and others.

    “Numerous studies have documented oncogenic properties of male steroid hormones and its derivatives on several human organs, including testis, liver, breast, and others (Sirianni et al., 2012; Salerno et al., 2018).”

    From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Salerno et al., 2018

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  1. [31]Handelsman DJ Androgen Physiology, Pharmacology and Abuse. [Updated 2016 Dec 12] De Groot LJ Chrousos G Dungan K Endotext South Dartmouth (MA) MDText.com, Inc 2000 https://www.ncbi.nlm.nih.gov/books/NBK279000/
  2. [95]Bergmann M Testicular biopsy, histology and TESE [Hodenbiopsie, histologie und TESE] Journal fur Urologie und Urogynakologie 2007 14 5 12

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Authors
Salerno, M., Cascio, O., Bertozzi, G., Sessa, F., Messina, A., Monda, V., Cipolloni, L., Biondi, A., Daniele, A., & Pomara, C.
Affiliations
  • University of Foggia (IT)
  • University of Catania (IT)
  • University of Campania "Luigi Vanvitelli" (IT)
  • Sapienza University of Rome (IT)
Corresponding author
Pomara, Cristoforo
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2018-04-10
Volume
9
Issue
27
Pages
19415-19426
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.24767
PMC
PMC5922407
OpenAlex
W2796715860
Cited by
71
References
107
Citations by year
2026: 3 · 2025: 16 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 8 · 2018: 3
FWCI
1.27
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
  • CINECA IRIS Institutial research information system (Parthenope University of Naples) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Pharmacological Effects and Assays
  • Social Sciences › Sociology and Political Science › Doping in Sports
Keywords
anabolic steroids, Leydig cell tumor, androgen receptor, dihydrotestosterone, 5α-reductase, estrogen receptor, aromatase, insulin-like growth factor I, PI3K/Akt signaling, nandrolone, stanozolol, DNA transcription, cell proliferation, breast cancer

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