Testis dysfunction by isoproterenol is mediated by upregulating endothelin receptor A, leptin and protein kinase Cɛ and is attenuated by an endothelin receptor antagonist CPU0213

This study has examined whether upregulation of endothelin receptor A, leptin and phosphorylated protein kinase Cɛ contributes to stress-induced testicular damaged and its possible reversal by endothelial (ET) antagonism. Adult male Sprague–Dawley rats were randomly divided into control and isoproterenol (ISO 1 mg/kg, subcutaneous (s.c.), 10 days) groups, and intervened with the ET receptor antagonist CPU0213 (20 mg/kg, s.c.), on days 6–10. In ISO group, testicular succinate dehydrogenase, lactate dehydrogenase, acid phosphotase, and γ-glutamyl transpeptidase, and serum testosterone decreased, whereas FSH increased, relative to control. The seminiferous tubules were damaged in association with testicular upregulation of protein abundance of leptin and pPKCɛ, and mRNA and protein expression of leptin receptor (OBRb) and ETA. CPU0213 was effective in ameliorating these abnormalities. Over-expression of ETA and leptin accounting for the testis dysfunction is likely to be mediated by pPKCɛ in the ISO treated rats. The upregulated ET pathway appears to be critical in pathologies of the testis.