Effect of testosterone drug on RAGE and inflammatory transcription factor NF-kB in rat testicular tissue at the fructose-enriched diet

Hypogonadism develops in diabetes mellitus (DM) and metabolic syndrome (MS). Testosterone replacement therapy may be applied, but its effect on spermatogenesis is controversial. Hyperglycemia promotes accumulation of glycation products. Cellular receptors for advanced glycation end products (RAGE) trigger inflammatory responses via the proinflammatory transcription factor NF-kB. This signaling pathway may be involved in impairment of spermatogenesis in hyperglycemia and during testosterone therapy. Hence, the aim of our study was to evaluate the effect of testosterone on RAGE and NF-kB levels in rat’s testicles in DM and MS. The experiments were carried out in young rats. The animals were randomly divided into several groups: K (intact animals, n = 6), metabolic syndrome (MS, n = 5), metabolic syndrome + testosterone treatment (MS + Tn, n = 8), testosterone (Tn, n = 4). Experimental data were obtained using Western blotting and immunofluorescence studies. No significant changes were found in RAGE and NF-kB contents in testicular tissue of rats with hyperglycemia, probably, due to insufficient duration of hyperglycemia and mechanisms that inhibit inflammation. The testicular RAGE content was significantly higher in MS + Tn, and Tn groups (Western blotting), as well as in MS + Tn group (immunofluorescence technique). Testosterone, in presence of hyperglycemia is likely to cause an increase of testicular RAGE content. No significant changes were found in testicular NF-kB contents. It seems that the inflammatory cascade mediated by this factor is not activated in the testicles. No significant changes were found in testicle-to-body mass ratio and of lumen area to wall area of seminiferous tubules ratio. These facts suggest the absence of atrophic changes in rat testes. Hence, the 6-week hyperglycemia does not cause an increase in the RAGE and NF-kB levels in rat testes; testosterone increases the RAGE content in rat testicles, both in presence of hyperglycemia and in the intact animals. Despite the increased RAGE, activation of NF-kB-dependent proinflammatory cascade is not revealed, and testicular atrophy does not occur in rats.