Reproductive toxicology (Elmsford, N.Y.)

Anabolic-androgenic steroids induce apoptosis and NOS2 (nitric-oxide synthase 2) in adult rat Leydig cells following in vivo exposure.

PMID 23085480


Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone (T) predominantly taken as drugs of abuse. Using in vivo treatment of adult male rats we investigated the effects of testosterone enanthate (TE) a widely abused AAS, on apoptosis of Leydig cells. Increased T and decreased luteinizing hormone levels in serum and decreased intra-testicular T values were found in 2 and 10 weeks treated groups. Two weeks of TE-treatment stimulated the expression of inducible nitric oxide synthase (NOS2) followed by increased NO production, decreased mitochondrial membrane potential and increased prevalence of Leydig cell apoptosis. This was prevented by in vivo administration of androgen receptor blocker. The induced NOS2 level and apoptosis returned to control levels after 10 weeks of TE-treatment but testes contained fewer Leydig cells. Overall, AAS in addition to reduced steroidogenesis induce transient increase of Leydig cells apoptotic rate through mechanism associated with androgen receptor, most likely involving NOS2 induction.