New evidence for SPX2 in regulating the brain-pituitary reproductive axis of half-smooth tongue sole (Cynoglossus semilaevis)

Abstract

Spexin (SPX) is an evolutionarily conserved neuropeptide, which was first identified in human proteome by data mining. Two orthologs (SPX1 and SPX2) are present in some non-mammalian species, including teleosts. It has been demonstrated that SPX1 is involved in reproduction and food intake, whereas the functional role of SPX2 is still absent in any vertebrate. The aim of the current study was to evaluate the actions of intraperitoneal injection of endogenous SPX2 peptide on the expression levels of some key reproductive genes of the brain-pituitary axis in half-smooth tongue sole. Our data showed an inhibitory action of SPX2 on brain gnih, spx1, tac3 and pituitary gthα, lhβ mRNA levels. However, SPX2 had no significant effect on brain gnihr, gnrh2, gnrh3, kiss2, kiss2r, spx2 expression or pituitary gh expression. On the other hand, SPX2 induced an increase in pituitary fshβ expression. Taken together, our results provide initial evidence for the involvement of SPX2 in the regulation of reproduction in vertebrates, which is in accordance with previous studies on SPX1.

Advances in research on spexin-mediated regulation of reproductive function in vertebrates

“…In half-smooth tongue sole, intraperitoneal injection of spexin-1 and spexin-2 resulted in a decreased abundance of gthα mRNA in the pituitary gland. However, spexin-1 downregulated fshβ , whereas spexin-2 downregulated lhβ ( 13 , 26 ). In summary, regardless of the paralogous type, spexin generally exhibits direct or indirect inhibitory effect on the pituitary gland and the release of gonadotropins in fish and birds, except for sheep.…”

“…Intraperitoneal injection of spexin-1 in half-smooth tongue sole increased the expression levels of hypothalamic gnrh3 and gnih , whereas gnrh2 transcript levels remained unaffected ( 13 ). Administration of spexin-2 appears to have no effect on gnrh2/3 expression, suggesting that the GnRH system may not be an essential target of spexin-2 in reproduction ( 26 ). Interestingly, researchers have also investigated the effects of spexin-2 on the autocrine and paracrine regulation of the spexin system.…”

“…Interestingly, researchers have also investigated the effects of spexin-2 on the autocrine and paracrine regulation of the spexin system. Peripheral injection of spexin-2 downregulates the mRNA expression of spx-1 with no effect on spx-2 expression ( 26 ). However, despite the progressive downregulation of spx expression during ovarian structural and follicular development in orange-spotted grouper, peripheral injection of spexin does not affect the expression of gnrh ( 11 ).…”