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The neuropeptide orexin A – search for its possible role in regulation of steroidogenesis in adult mice testes
Author(s) -
Joshi D.,
Singh S. K.
Publication year - 2018
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12475
Subject(s) - orexin , endocrinology , medicine , orexin a , antagonist , neuropeptide , receptor antagonist , orexin receptor , receptor , biology , neuropeptide y receptor
Summary 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 in vivo and ex vivo conditions. Mice were given a single bilateral intratesticular injection of the antagonist at doses of 4 and 12 μg/mouse and were sacrificed 24 h 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 (E 2 ) 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 ex vivo study, antagonist treatment to the testis caused a marked decrease in the level of T and an increase in the level of E 2 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 ex vivo study supported the findings of in vivo 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.