The nonapeptide isotocin in goldfish: Evidence for serotonergic regulation and functional roles in the control of food intake and pituitary hormone release

Nonapeptides are a highly conserved family of peptides synthesized in the neuroendocrine brain and acting on central and peripheral receptors to regulate physiological functions in vertebrates. While the evolution of the two gene families of oxytocin-like and vasopressin-like nonapeptides and their receptors, as well as the neuroanatomy of their independent neuronal circuits have been well-characterized across vertebrate species, comparative studies on the physiological roles across vertebrates are lagging behind. In the current study, we focused on the comparative neuroendocrine functions and regulation of isotocin, the teleost homologue of mammalian oxytocin. Specifically, we address the hypothesis that isotocin exerts opposing effects on food intake and reproduction, which are well-established effects of its homologue oxytocin in mammalian species. Using goldfish, a well-characterized model of neuroendocrine regulation of both food intake and reproduction, we here showed that isotocin acts as an anorexigenic factor while exerting stimulatory effects on pituitary luteinizing hormone and growth hormone release. Given the dual inhibitory and stimulatory roles of serotonin on food intake and pituitary release of reproductive hormone in goldfish, we also investigated the potential crosstalk between both systems using immunohistochemistry and pharmacological approaches. Results provide neuroanatomical and pharmacological evidence for serotonergic regulation of magnocellular isotocinergic neurons in the preoptic area and pituitary. Together, these findings firstly provide the basis to investigate neuroendocrine cross-talk between serotonergic and nonapeptidergic systems in the regulation of both food intake and reproduction in goldfish, and secondly point to a conserved function of oxytocin-like peptides in the differential neuroendocrine control of both physiological processes in vertebrates.