Central Relaxin-3 Administration Causes Hyperphagia in Male Wistar Rats

• Published in: Endocrinology (Philadelphia) 2005-08, Vol.146 (8), p.3295-3300
• Main Authors: McGowan, B. M. C, Stanley, S. A, Smith, K. L, White, N. E, Connolly, M. M, Thompson, E. L, Gardiner, J. V, Murphy, K. G, Ghatei, M. A, Bloom, S. R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain stem; Central nervous system; Cerebral Ventricles - drug effects; Cerebral Ventricles - physiology; Feeding behavior; Food; Food intake; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - drug effects; Hyperphagia; Hyperphagia - chemically induced; Hypothalamus; Hypothalamus - physiopathology; Injections, Intraventricular; Male; Males; Midline Thalamic Nuclei - drug effects; Midline Thalamic Nuclei - physiology; Neuropeptide Y; Neuropeptide Y - genetics; Paraventricular nucleus; Pro-Opiomelanocortin - genetics; Proopiomelanocortin; Rats; Rats, Wistar; Receptors; Relaxin; Relaxin - administration & dosage; Relaxin - pharmacology; RNA, Messenger - genetics; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2004-1532

Relaxin-3 (INSL-7) is a recently discovered member of the insulin superfamily. Relaxin-3 mRNA is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 binds with high affinity to the LGR7 receptor and to the previously orphan G protein-coupled receptor GPCR135. GPCR135 mRNA is expressed predominantly in the central nervous system, particularly in the paraventricular nucleus (PVN). The presence of relaxin-3 and these receptors in the PVN led us to investigate the effect of central administration of relaxin-3 on food intake in male Wistar rats. The receptor involved in mediating these effects was also investigated. Intracerebroventricular injections of human relaxin-3 (H3) to satiated rats significantly increased food intake 1 h post administration in the early light phase [0.96 ± 0.16 g (vehicle) vs. 1.81 ± 0.21 g (180 pmol H3), P < 0.05] and the early dark phase [2.95 ± 0.45 g (vehicle) vs. 4.39 ± 0.39 g (180 pmol H3), P < 0.05]. Intra-PVN H3 administration significantly increased 1-h food intake in satiated rats in the early light phase [0.34 ± 0.16 g (vehicle) vs. 1.23 ± 0.30 g (18 pmol H3), P < 0.05] and the early dark phase [4.43 ± 0.32 g (vehicle) vs. 6.57 ± 0.42 g (18 pmol H3), P < 0.05]. Feeding behavior increased after intra-PVN H3. Equimolar doses of human relaxin-2, which binds the LGR7 receptor but not GPCR135, did not increase feeding. Hypothalamic neuropeptide Y, proopiomelanocortin, or agouti-related peptide mRNA expression did not change after acute intracerebroventricular H3. These results suggest a novel role for relaxin-3 in appetite regulation.