Expression of E-SOD, GPX5 mRNAs and immunoexpression of Cu/ZnSOD in epididymal epithelial cells of finasteride-treated rats

Abstract

We studied the immunoexpression of Cu/Zn superoxide dismutase (Cu/ZnSOD) and mRNAs expression of extracellular superoxide dismutase (E-SOD), and epididymal specific glutathione peroxidase 5 (GPX5), in epithelial cells of caput and cauda epididymis of rats treated with finasteride, a steroid-based inhibitor of 5alpha-reductase. The 5alpha-reductase is known to exist in two isoforms. Both 5alpha-red1 and 5alpha-red2 catalyse the irreversible conversion of T into DHT. Formation of DHT in the epididymis is mostly due to the action of 5alpha-red2 and finasteride is more potent inhibitor of this isoform. Rats were treated with finasteride for 56 days covering the duration of one spermatogenesis (four cycles of the seminiferous epithelium). Although E-SOD mRNA is normally expressed in cells of cauda but not of caput epididymis, treatment with finasteride produced the E-SOD transcript in cells of caput epididymis too. The GPX5 transcript was detected in cells of caput epididymis of control and experimental rats, but the level of expression measured densitometrically was significantly lower in finasteride-treated rats. The immunoexpression of Cu/ZnSOD was also changed in epididymis of finasteride-treated rats. Finasteride appears to change the pattern of expression of antioxidant enzymes and may alter the protective function of the epididymis in relation to spermatozoa.

DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions

“…Therefore, in our study (carried out with mature rats), we inhibited the 5a-red2 activity by finasteride, which is used in basic and clinical studies as the one of the best inhibitors of the enzyme [23,30]. In our previous studies, we had found that 28 and 56 day DHT-deficiency altered the androgen receptor (AR) [31], estrogen a and b receptors (ERa, ERb) in epididymis [32], antioxidant enzymes (GPX5, E-SOD, Cu/Zn SOD) [33] and inducible nitric oxide synthase (iNOS) [34] expression patterns. The changes in the morphology of testes were noticed after a long period (56 days) of androgen imbalance [35].…”

Antioxidant enzyme expression of mRNA and protein in the epididymis of finasteride-treated male rat offspring during postnatal development

“…In general, other male reproductive toxins such as chlorpyrifos (insecticide) [87], atrazine (pesticide) [60], and nonylphenol (ED) [56], that postnatally influence an organism also caused a reduction in plasma testosterone concentration. Similarly, the inhibition of 5α-reductase 2 activity by finasteride changed plasma androgen concentrations in finasteride-treated adult male rats [37] and in male offspring of these rats [38]. The differences in androgen levels between the F1:Fin and F1:Control groups of rats exhibit some resemblance to the results of studies which explored prenatal exposure to anti-androgenic endocrine disruptors such as flutamide [88] or vinclozolin [89] that reduced serum testosterone concentrations in adult animals.…”

“…Methoxychlor similarly decreased the activity of antioxidant enzymes (SOD, CAT, GR, GPX) in the epididymis with respect to the regions of the organ [59]. The study by Kolasa et al [37] demonstrated that finasteride treatment of adult rats changed the epididymal region-specific immunoexpression of antioxidant enzymes (GPX5: increase in the caput of treated rats compared to control rats; E-SOD: increase in the caput and decrease in the cauda of treated rats). Also, treatment of Wistar male rats with ethanol and atrazine showed diverse results: CAT activity in epididymal homogenates decreased, SOD and GPX activity increased [60].…”

“…The following primer pairs were used: for Cat (F: ATG GCT TTT GAC CCA AGC AA; R: CGG CCC TGG AGC ATC TTG T), for Sod1 (F: CAC TCT AAG AAA CAT GGC G; R: CTG AGA GTG AGA TCA CAC G), for Gpx5 (F: CAC CCC TCA GAG ACT GTG GT; R: TTG ACA GTG CTG ACA GGA GC) and for Gsr (F: GGA AGT CAA CGG GAA AAA GTT CAC TG; R: CAA TGTA ACC GGC ACC CAC AAT AAC). The primer sequences used in the study were obtained from the references [37,46,47], modified according to the sequence information obtained from the NCBI database, and were synthesized by Oligo.pl (IBB PAN, Poland).…”

“…In our previous study we showed that treatment with finasteride (an inhibitor of 5α-reductase type 2) in adult male rats influenced the patterns of E-SOD, GPX5, and Cu/ZnSOD expression; that change was region-dependent and the expression was up-or down-regulated compared to control animals [37]. Recently, we also found that finasteride treatment of paternal rats resulted in altered serum and intratesticular levels of testosterone (T) and dihydrotestosterone (DHT) in their male offspring [38,39].…”