Expression and role of receptor 1 for orexins in seminiferous tubules of rat testis

Abstract

Orexins (OxA and OxB) and their receptors (Ox1R and Ox2R), originally detected in the hypothalamus, have also been localized in multiple cerebral areas and peripheral organs. Thus, in addition to their central function in the regulation of food intake, arterial blood pressure, heart rate, sleep/wake cycle, sexual behaviour, arousal, and hypothalamic/hypophyseal axis, these neuropeptides may exert a local action in various peripheral organs and tissues. Emerging evidence suggests a main role of OxA and its highly specific receptor Ox1R in the male genital tract of mammals. We previously demonstrated OxA localization in Sertoli cells and spermatids of rat testis. Here, we show positive stainings of Ox1R in developing spermatocytes, and spermatids of rat testis by immunohistochemistry. The expression of Ox1R mRNA and the protein in the tissue was also established by reverse-transcription polymerase chain reaction and Western blotting respectively. The addition of OxA to fresh testis slices significantly increased testosterone (T) secretion which, conversely, was inhibited by Mullerian inhibiting substance (MIS). The sequential treatment of testis samples with the two substances highlighted an antagonizing activity of OxA versus MIS in regulating T levels. Furthermore, the stimulating effect on T production by OxA was prevented by the addition of the selective Ox1R inhibitor SB-408124. Overall, our findings suggest that locally secreted OxA interacting with Ox1R activates signals which antagonize MIS action in the control of T levels in mammalian testis.

Localization of orexin B and receptor 2 for orexins in testicular cytotypes of the camelid alpaca (Vicugna pacos)

“…The presence of OX 1 in mammalian Leydig cells suggested that OxA could play a role in testicular steroidogenesis (Assisi et al., ; Barreiro et al., ; Liguori et al., ). Particularly, it was hypothesized that OxA, mainly produced by the tubular Sertoli cells, could act on its same source by an autocrine modality of action decreasing the production of Müllerian inhibiting substance (MIS), which is a steroidolitic compound basically synthesized in these cells (Teixeira, Fynn‐Thompson, Payne, & Donahoe, ).…”

“…Particularly, it was hypothesized that OxA, mainly produced by the tubular Sertoli cells, could act on its same source by an autocrine modality of action decreasing the production of Müllerian inhibiting substance (MIS), which is a steroidolitic compound basically synthesized in these cells (Teixeira, Fynn‐Thompson, Payne, & Donahoe, ). The consequent stimulation of testosterone production was experimentally assessed through the sequential in vitro addition of OxA and MIS, and vice versa, to slices of rat and alpaca testis (Assisi et al., ; Liguori et al., ). To test a potential steroidogenic effect of OxB in the male gonad, an experimental study was performed on in vitro cultured rat testis slices (Liguori et al., ) in which the steroidogenic activity of OxA was confirmed, but, conversely, OxB was found to be ineffective on testosterone production.…”

“…More recently, the orexins and their receptors, beyond referred as the orexinergic complex, were found to be present in the adrenals and in other peripheral organs belonging to the gastrointestinal and genital tract. Particularly, the presence of OxA, prepro‐orexin and OX 1 has been detected in the principal cells of the epididymis and in some testicular cytotypes of the rat and alpaca (Assisi et al., ; Liguori et al., , ; Pavone, Tafuri, Avallone, Staiano, & Vittoria, ; Tafuri et al., , ), in the urethro‐prostatic complex of cattle (Russo et al., ) and in the normal, hyperplastic and carcinomatous prostate of humans (Valiante et al., , ). The expression of OX 1 mRNA has been described in the testis of sheep (Zhang et al., ) and chicken (Ohkubo, Tsukada, & Shamoto, ) and in the seminal vesicles, penis and epididymis of men (Karteris, Chen, & Randeva, ).…”

Expression of orexin A and its receptor 1 in the human prostate

“…In the male genital tract, the principal cells of rat epididymis ) and the Sertoli cells of rat testes (Barreiro et al 2005;Tafuri et al 2010) have been shown to provide a local source of OXA. Expression of OX1R mRNA in the seminal vesicles, penis and epididymis of humans (Karteris et al 2004), in the testes of sheep (Zhang et al 2005), chicken (Ohkubo et al 2003) and rat (J€ ohren et al 2001;Barreiro et al 2004;Assisi et al 2012), and in the rat epididymis ) has been demonstrated. By contrast, contradictory results on the localization of the peptide and its receptor 1 in the prostate have been reported.…”

Radiosynthesis and evaluation of [11C]EMPA as a potential PET tracer for orexin 2 receptors

“…4 Recent research also suggests that orexin receptors may be related or contribute to several disorders in peripheral organs. 5 Although they have diverse functions, orexin receptors have been most extensively investigated for their roles in CNS and have been aggressively pursued as therapeutic targets for sleeping disorders. 6 The two members of the family, orexin-A (33 amino acids) and orexin-B (28 amino acids), are derived from the same biological precursor.…”