Stanozolol administration combined with exercise leads to decreased telomerase activity possibly associated with liver aging

Abstract

Anabolic agents are doping substances which are commonly used in sports. Stanozolol, a 17α‑alkylated derivative of testosterone, has a widespread use among athletes and bodybuilders. Several medical and behavioral adverse effects are associated with anabolic androgenic steroids (AAS) abuse, while the liver remains the most well recognized target organ. In the present study, the hepatic effects of stanozolol administration in rats at high doses resembling those used for doping purposes were investigated, in the presence or absence of exercise. Stanozolol and its metabolites, 16‑β‑hydroxystanozolol and 3'‑hydroxystanozolol, were detected in rat livers using liquid chromatography‑mass spectrometry (LC‑MS). Telomerase activity, which is involved in cellular aging and tumorigenesis, was detected by examining telomerase reverse transcriptase (TERT) and phosphatase and tensin homolog (PTEN) expression levels in the livers of stanozolol‑treated rats. Stanozolol induced telomerase activity at the molecular level in the liver tissue of rats and exercise reversed this induction, reflecting possible premature liver tissue aging. PTEN gene expression in the rat livers was practically unaffected either by exercise or by stanozolol administration.

Figure 1

Telomeres are protective caps of chromosomes (59) (adapted with permission from Shutterstock).

Figure 2

Telomerase adds telomeric repeats (TTAGGG) to the 3′-hydroxyl end of the leading strand of the telomere. The RNA component serves as the template for nucleotide addition. This is the Telomerase Complex and it consists of the reverse transcriptase component (TERT), the RNA component (TERC), the protein Dyskerin and other associated proteins (NHP2, NOP10 and GAR1).

Figure 3

Scatter diagram of TERT gene expression and percentage relative telomerase activity. TERT, telomerase reverse transcriptase.

Figure 4

Scatter diagram of 3′-hydroxystanozolol and percentage relative telomerase activity.

Figure 5

Immunohistochemical staining of PTEN and TERT proteins in all experimental groups (scale bar, 50 μm). The rat groups were as follows: i) The control (C) group; ii) the propylene treatment (PG) group; iii) the stanozolol treatment (ST) group; iv) the propylene treatment and exercise (PGE) group; and v) the stanozolol treatment and exercise (STE) group. PTEN, phosphatase and tensin homolog protein, TERT, telomerase reverse transcriptase.