Adropin may promote insulin stimulated steroidogenesis and spermatogenesis in adult mice testes

Abstract

Adropin is a versatile peptide which was discovered as a novel metabolic hormone that is involved in the regulation of lipid and glucose homeostasis. However, its possible role in the testicular function is not yet understood. The aim of our study was to explore the distribution pattern of adropin and GPR19 in various cell types and its possible role in testicular functions of adult mice. Immunohistochemical study revealed the intense immunoreactivity of adropin in the Leydig cells, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells and primary as well as secondary spermatocytes in mouse testis. Enho mRNA was also found to be expressed in the mouse testis. These findings suggested that adropin-GPR19 signaling may act in autocrine/paracrine manner to modulate testicular functions. Furthermore, to find out the direct role of adropin in the testicular function, in vitro study was performed in which testicular slices were cultured with adropin alone (10 and 100 ng/mL) and in combination with insulin (5 μg/mL). Adropin alone inhibited testicular testosterone synthesis by inhibiting the expression of P450-SCC, 3β-HSD, and 17β-HSD while along with insulin stimulated the testicular testosterone synthesis by increasing the expression of GPR19, IR, StAR, P450-SCC, 3β-HSD, and 17β-HSD. Adropin alone or in combination with insulin promoted germ cell survival and proliferation by upregulating the expression of PCNA, Bcl2, and pERK1/2. Thus, it can be concluded that adropin-GPR19 signaling promotes insulin stimulated steroidogenesis and germ cell survival as well as proliferation in the mice testes in an autocrine/paracrine manner.