Pattern of Orexin Expression and Direct Biological Actions of Orexin-A in Rat Testis

Abstract

Orexins, hypothalamic neuropeptides initially involved in the control of food intake and sleep-wake cycle, have recently emerged as pleiotropic regulators of different biological systems, including the reproductive axis. Besides central actions, peripheral expression and functions of orexins have been reported, and prepro-orexin and orexin type-1 receptor mRNAs have been detected in the testis. However, the pattern of expression and biological actions of orexin in the male gonad remain mostly unexplored. In this study, we report analyses on testicular prepro-orexin mRNA expression and orexin-A immunoreactivity in different experimental settings, and on direct effects of orexin-A on seminiferous tubule functions. Expression of prepro-orexin mRNA was demonstrated in the rat testis at different stages of postnatal development, with negligible levels at early juvenile period and maximum values in adulthood. Likewise, orexin-A immunoreactivity was demonstrated along postnatal maturation, with strong peptide signal in Leydig cells and spermatocytes at specific stages of meiosis. Testicular expression of prepro-orexin mRNA appeared hormonally regulated; its levels decreased after hypophysectomy and increased after gonadotropin replacement and ghrelin stimulation. Finally, orexin-A suppressed the expression of key Sertoli cell genes, such as Müllerian-inhibiting substance and stem cell factor, and inhibited DNA synthesis in specific stages of the seminiferous epithelium. In conclusion, we provide evidence for the regulated expression of orexin in the rat testis and its potential involvement in the control of seminiferous tubule functions. Together with our recent results on the expression of orexin type-1 receptor in the rat testis, our data further document a novel testicular site of action of orexins in the control of male reproductive axis.

Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation

“…Finally, in the reproductive front, we have obtained preliminary evidence that, as is the case for other central and peripheral regulators of food intake and energy balance, such as ghrelin, resistin, adiponectin, and orexin (Nogueiras et al 2004, Barreiro et al 2005, Caminos et al 2008, Tena-Sempere 2008, NUCB2/ nesfatin-1 is also expressed in the gonads. Thus, we have detected NUCB2 mRNA expression in human, rat, and mouse testis, as well as in the rat ovary (García-Galiano, Gaytan & Tena-Sempere, manuscript in preparation).…”

Immunohistochemical expression and distribution of orexin, orphanin and leptin in the major salivary glands of some mammals

“…It was identified for the first time in white and brown adipose tissue, and then in many other cells, including chief cells in human oxyntic glands [23][24][25] and gastroenteropancreatic system (GEP) of Zucker rats. Further unexpected localization of these three mediators of energy balance in other areas which are not associated with the regulation of energy metabolism, such as the urogenital [26,27] and respiratory systems, adrenal glands [28] and testis [29], suggest new functional roles performed by these peptides.…”

Expression of Orexin A and Its Receptor 1 in the Vestibular Glands of the Cattle Genital Tract

“…The amine, in fact, is the main product of the NE cells scattered along the urogenital tract of humans of both sexes (Fetissof et al, 1983), dog (Hanyu et al, 1987), and sheep (Vittoria et al, 1990). Furthermore, 5-HT and oxA have been found in Leydig cells of hamster (Frungieri et al, 1999) and rat (Barreiro et al, 2005) testis, where they regulate steroidogenesis through an antagonistic mechanism of action.…”

“…Recently, their presence has also been demonstrated in endocrine cytotypes belonging to the gastrointestinal tract, pancreas, adrenal glands, and testis (Randewa et al, 2001;Karteris et al, 2004;Barreiro et al, 2005;Ehrström et al, 2005;Zhang et al, 2005). Thus, orexins are considered both neuropeptides and hormones.…”