Abstract
Orexin A, a hypothalamic neuropeptide, regulates food intake and sleep-wake cycle by binding to orexin receptor 1. Besides brain, orexin A and orexin receptor 1 are also present in peripheral organs. In our earlier studies, localization and expression of orexin A and orexin receptor 1 have been shown in adult mouse testis, and further their role in testicular development in neonatal mouse was also demonstrated. In this study, role of orexin A and orexin receptor 1 in the testis of adult mouse by blocking binding of orexin A to orexin receptor 1 using an orexin receptor 1 antagonist, SB-334867, was investigated under invivo and exvivo conditions. Mice were given a single bilateral intratesticular injection of the antagonist at doses of 4 and 12μg/mouse and were sacrificed 24h post-injection. The antagonist treatment caused degenerative changes in the seminiferous tubules in the testis and also caused alterations in steroidogenesis, with a concomitant decrease in the level of testosterone (T) and an increase in the level of 17β-estradiol (E2 ) in serum and in testis. Further, expressions of SF1, StAR, P450scc and 17β-HSD were downregulated, while the expressions of 3β-HSD and P450arom were upregulated in antagonist-treated mice compared with controls. Also, the oxidative stress in the testis was increased in treated mice. In exvivo study, antagonist treatment to the testis caused a marked decrease in the level of T and an increase in the level of E2 in the media, accompanied by downregulated expression of SF1, StAR, P450scc and 17β-HSD and an upregulation in the expression of 3β-HSD and P450arom, indicating a direct role of orexin A in regulation of testicular steroidogenesis. The results of exvivo study supported the findings of invivo study. In conclusion, the results suggest potential involvement of orexin A and orexin receptor 1 in regulation of steroidogenesis and spermatogenesis in the testis of adult Parkes mice.
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