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

Author(s): Cheng YS, Dai DZ, Dai Y

Affiliation(s): Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.

Publication date & source: 2010-07, Reprod Toxicol., 29(4):421-6. Epub 2010 Mar 20.

Publication type: Research Support, Non-U.S. Gov't

This study has examined whether upregulation of endothelin receptor A, leptin and phosphorylated protein kinase Cvarepsilon 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 1mg/kg, subcutaneous (s.c.), 10 days) groups, and intervened with the ET receptor antagonist CPU0213 (20mg/kg, s.c.), on days 6-10. In ISO group, testicular succinate dehydrogenase, lactate dehydrogenase, acid phosphotase, and gamma-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 pPKCvarepsilon, and mRNA and protein expression of leptin receptor (OBRb) and ET(A). CPU0213 was effective in ameliorating these abnormalities. Over-expression of ET(A) and leptin accounting for the testis dysfunction is likely to be mediated by pPKCvarepsilon in the ISO treated rats. The upregulated ET pathway appears to be critical in pathologies of the testis.