Anorectic actions of prolactin-releasing peptide are mediated by corticotrophin-releasing hormone receptors

Prolactin-releasing peptide and corticotrophin-releasing hormone R-00402-2003.R1 2 Prolactin-releasing peptide (PrRP) reduces food intake and body weight, and modifies body temperature when administered centrally in rats, suggesting a role in energy homeostasis. However, the mediators of PrRP's actions are unknown. The present study, therefore, firstly examined the possible involvement of the anorectic neuropeptides, corticotrophin-releasing hormone (CRH) and the melanocortins (e.g. α-melanocyte stimulating hormone) in PrRP's effects on food intake and core body temperature, and secondly determined if PrRP affects energy expenditure by measuring oxygen consumption (VO 2). Intracerebroventricular (icv) injection of PrRP (4 nmol) to 24h fasted male Sprague-Dawley rats decreased food intake and modified body temperature. Blockade of central CRH receptors by icv co-administration of the CRH receptor antagonist, astressin (20 µg), reversed the PrRP-induced reduction in feeding. However, astressin's effect on PrRP-induced changes in body temperature was complicated, since the antagonist itself caused a slight rise in body temperature. In contrast, icv co-administration of the melanocortin receptor-3/4 antagonist, SHU9119 (0.1 nmol), had no effect on any of PrRP's actions. Finally, icv injection of PrRP (4 nmol) caused a significantly greater VO 2 over a 3 h test period compared with vehicle-treated rats. These results show that the anorectic actions of PrRP are mediated by central CRH receptors, but not by melanocortin receptors-3/4, and that PrRP can modify VO 2. Prolactin-releasing peptide and corticotrophin-releasing hormone R-00402-2003.R1 3 Prolactin-releasing peptide (PrRP) was first identified to be the endogenous ligand for the human orphan receptor, GPR10/hGR3 (or UHR-1 in the rat), and was reported to display specific prolactin-releasing properties (15). PrRP mRNA and immunoreactive cell bodies are located exclusively in three brain regions, the dorsomedial hypothalamus (DMH), and in the nucleus tractus solitarius (NTS) and the (PrRP-R) mRNA is also found in the rat brain, and is expressed most highly in the reticular nucleus of the thalamus, the periventricular hypothalamic nucleus, paraventricular hypothalamic nucleus (PVN), DMH, NTS and the area postrema (7, 19, 22, 39). PrRP-immunoreactive fibers are detected in several brain regions that express PrRP-R mRNA, including the PVN and the periventricular hypothalamic nucleus (18, 30, 60). We have proposed a role for PrRP in energy homeostasis, since mRNA for the peptide is reduced, typically for an anorectic peptide, in states of negative energy balance (fasting and lactation) and in the obese Zucker rat (5, 22). Intracerebroventricular (icv) administration of PrRP reduces both fast-induced and spontaneous feeding, and bodyweight gain in …