Downregulation of prolactin-releasing peptide gene expression in the hypothalamus and brainstem of diabetic rats.
ABSTRACT We investigated the prolactin-releasing peptide (PrRP) mRNA levels in the hypothalamus and brainstem of streptozotocin (STZ)-induced diabetic rats and fa/fa Zucker diabetic rats, using in situ hybridization histochemistry. PrRP mRNA levels in the hypothalamus and brainstem of STZ-induced diabetic rats were significantly reduced in comparison with those of control rats. PrRP mRNA levels in the diabetic rats were reversed by both insulin and leptin. PrRP mRNA levels in the fa/fa diabetic rats were significantly reduced in comparison with those of Fa/? rats. PrRP mRNA levels in the fa/fa diabetic rats were significantly increased by insulin-treatment, but did not reach control levels in the Fa/? rats. We also investigated the effect of restraint stress on PrRP mRNA levels in STZ-induced diabetic rats. The PrRP mRNA levels in the control and the STZ-induced diabetic rats increased significantly after restraint stress. The diabetic condition and insulin-treatment may affect the regulation of PrRP gene expression via leptin and other factors, such as plasma glucose level. The diabetic condition may not impair the role of PrRP as a stress mediator.
- SourceAvailable from: Tatsushi Onaka[Show abstract] [Hide abstract]
ABSTRACT: Oxytocin neurones are activated by stressful stimuli, food intake and social attachment. Activation of oxytocin neurones in response to stressful stimuli or food intake is mediated, at least in part, by noradrenaline/prolactin-releasing peptide (PrRP) neurones in the nucleus tractus solitarius, whereas oxytocin neurones are activated after social stimuli via medial amygdala neurones. Activation of oxytocin neurones induces the release of oxytocin not only from their axon terminals, but also from their dendrites. Oxytocin acts locally where released or diffuses and acts on remote oxytocin receptors widely distributed within the brain, resulting in anxiolytic, anorexic and pro-social actions. The action sites of oxytocin appear to be multiple. Oxytocin shows anxiolytic actions, at least in part, via serotoninergic neurones in the median raphe nucleus, has anorexic actions via pro-opiomelanocortin neurones in the nucleus tractus solitarius and facilitates social recognition via the medial amygdala. Stress, obesity and social isolation are major risk factors for mortality in humans. Thus, the oxytocin-oxytocin receptor system is a therapeutic target for the promotion of human health.Journal of Neuroendocrinology 02/2012; 24(4):587-98. · 3.51 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: We have recently identified prolactin (PRL)-releasing peptides (PrRPs) and their stimulating effects on feeding behaviour in chicks. To investigate further metabolic functions of PrRP, the present study was performed to clarify whether intracerebroventricular (ICV) injection of PrRP31, an active form of PrRP in chicks, affects heat production (HP), respiratory quotient (RQ) and plasma concentrations of metabolic fuels in chicks. The ICV injection of PrRP31 (94 and 375 pmol) did not affect HP but significantly lowered RQ. The change in RQ implies that PrRP31 shifted the utility of metabolic fuels in the body. This idea was confirmed by subsequent results in which ICV injection of PrRP31 significantly reduced glucose but increased non-esterified fatty acid concentrations in plasma. These shifts in blood metabolic fuels would not be through the increased plasma insulin, because the ICV injection of PrRP31 significantly decreased plasma insulin concentration. On the other hand, ICV injection of another orexigenic peptide, neuropeptide Y (NPY) also induced the insulin release and the metabolic effects were similar to those of PrRP31. Because ICV injection of PrRP31 increased NPY mRNA in the diencephalon, the NPY may mediate the metabolic functions of PrRP31. In summary, the present study suggests that central PrRP31 shifts the utilities of peripheral energy sources, which is not via hyperinsulinemia but via the diencephalon.Physiology & Behavior 06/2013; · 3.16 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Abstract: Prolactin-releasing peptide (PrRP) was first isolated from bovine hypothalamus as an orphan G-protein-coupled receptor using the strategy of reverse pharmacology. PrRP is expressed specifically in the human pituitary and is identified in the hypothalamus as a potent prolactin-releasing factor (PRF) for anterior pituitary cells. The initial studies showed that PrRP was a potent and specific prolactin-releasing factor; however our studies in the pituitary demonstrated that PrRP is more important such as modulator of prolactin release mediated by thyroid-releasing hormone (TRH) than PRF itself. However, physiological studies indicated that PrRP might play a wide range of roles in neuroendocrinology other than prolactin release, i.e., sleep regulation, metabolic homeostasis, food intake, stress responses or cardiovascular regulation. Over 150 papers and several patents have been published on this subject since its initial discovery in 1998. Herein, I review the state of current knowledge of the PrRP system, especially its roles in brain functions and implications for therapy.Immun., Endoc. & Metab. Agents in Med. Chem. 01/2011; 11.