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APPETITE, OBESITY AND METABOLISM

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

Catherine B. Lawrence,¹ Yong-Ling Liu,² Michael J. Stock,^2, and Simon M. Luckman¹

¹School of Biological Sciences, University of Manchester, Manchester M13 9PT; and ²Department of Physiology, St George's Hospital Medical School, London SW17 0RE, United Kingdom

Submitted 18 July 2003 ; accepted in final form 12 September 2003

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, first examined the possible involvement of the anorectic neuropeptides corticotropin-releasing hormone (CRH) and the melanocortins (e.g., -melanocyte-stimulating hormone) in PrRP's effects on food intake and core body temperature and, second, determined if PrRP affects energy expenditure by measuring oxygen consumption (O₂). Intracerebroventricular injection of PrRP (4 nmol) to 24-h-fasted male Sprague-Dawley rats decreased food intake and modified body temperature. Blockade of central CRH receptors by intracerebroventricular coadministration 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 because the antagonist itself caused a slight rise in body temperature. In contrast, intracerebroventricular coadministration of the melanocortin receptor-3/4 antagonist SHU-9119 (0.1 nmol) had no effect on any of PrRP's actions. Finally, intracerebroventricular injection of PrRP (4 nmol) caused a significantly greater O₂ 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 O₂.

food intake; astressin; SHU-9119; oxygen consumption; body temperature

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