Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats

• Published in: American journal of physiology: endocrinology and metabolism Vol. 292; no. 3; pp. E913 - E919
• Main Authors: McGowan, B. M, Stanley, S. A, White, N. E, Spangeus, A, Patterson, M, Thompson, E. L, Smith, K. L, Donovan, J, Gardiner, J. V, Ghatei, M. A, Bloom, S. R
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.03.2007
• Subjects: Animals; Brain; Brain Mapping; Eating - drug effects; Hormones; Hypothalamus - drug effects; Hypothalamus - physiology; Immunohistochemistry; Insulin; Intracellular Signaling Peptides and Proteins - metabolism; Male; MEDICIN; MEDICINE; Models, Biological; Nerve Tissue Proteins - pharmacology; Neurons; Neuropeptides - metabolism; Orexins; Peptides; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Wistar; Relaxin - pharmacology; Rodents
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00346.2006

Department of Metabolic Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom Submitted 14 July 2006 ; accepted in final form 22 November 2006 The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1 ) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2 ) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4 ± 0.2 (vehicle) vs. 2.9 ± 0.5 g (H3), P < 0.001; ARC 0.7 ± 0.3 (vehicle) vs. 2.7 ± 0.2 g (H3), P < 0.05; and APOA 0.8 ± 0.1 (vehicle) vs. 2.2 ± 0.2 g (H3), P < 0.05]. Cumulative food intake was significantly increased 8 h following administration into the SON and 4 h into the APOA. A significant increase in Fos-like immunoreactivity was seen in the SON following central relaxin-3 administration. Relaxin-3 stimulates feeding in several hypothalamic nuclei, and these studies provide additional support for relaxin-3 as an important peptide in appetite regulation. relaxin family peptide receptor 3; appetite; supraoptic nucleus; arcuate nucleus Address for reprint requests and other correspondence: S. Bloom, Dept. of Metabolic Medicine, Imperial College London, 6th Floor Commonwealth Bldg., Hammersmith Hospital, Du Cane Road, London W12 0NN, UK (e-mail: s.bloom{at}imperial.ac.uk )