Central relaxin-3 administration causes hyperphagia in male Wistar rats.
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.
McGowan
B M C
BM
Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom.
Stanley
S A
SA
Smith
K L
KL
White
N E
NE
Connolly
M M
MM
Thompson
E L
EL
Gardiner
J V
JV
Murphy
K G
KG
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006963:Hyperphagia / Q000139:chemically induced*; D007031:Hypothalamus / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D020644:Midline Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000008:administration & dosage* / Q000494:pharmacology*
D009478:Neuropeptide Y; C480238:RLN3 protein, human; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D012065:Relaxin