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

Monica Salerno, Orazio Cascio, Giuseppe Bertozzi, Francesco Sessa, Antonietta Messina, Vincenzo Monda, Luigi Cipolloni, Antonio Biondi, Aurora Daniele and Cristoforo Pomara _

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Oncotarget. 2018; 9:19415-19426. https://doi.org/10.18632/oncotarget.24767

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Abstract

Monica Salerno1, Orazio Cascio2, Giuseppe Bertozzi1, Francesco Sessa1, Antonietta Messina3, Vincenzo Monda3, Luigi Cipolloni4, Antonio Biondi5, Aurora Daniele6 and Cristoforo Pomara2

1University of Foggia, Department of Clinical and Experimental Medicine, Foggia, Italy

2University of Catania, Department of Medical, Surgical and Advanced Technologies, “G.F. Ingrassia”, Catania, Italy

3University of Campania “L. Vanvitelli”, Department of Experimental Medicine, Naples, Italy

4Università degli Studi di Roma “La Sapienza”, Department of Public Health, Roma, Italy

5University of Catania, Department of Surgery, Catania, Italy

6University 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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