Central relaxin-3 administration causes hyperphagia in male wistar rats

B. M.C. McGowan, S. A. Stanley, K. L. Smith, N. E. White, M. M. Connolly, E. L. Thompson, J. V. Gardiner, K. G. Murphy, M. A. Ghatei, S. R. Bloom

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156 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3295-3300
Number of pages6
JournalEndocrinology
Volume146
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

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