Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2005) 9 P124

Department of Metabolic Medicine, Imperial College, Hammersmith Campus, London, UK.


Relaxin-3 (INSL-7) is a recently discovered member of the insulin superfamily, a group of structurally related hormones whose precursors have a domain arrangement similar to that of pro-insulin. Relaxin-3 mRNA is expressed in the nucleus incertus of the brainstem which has projections to the hypothalamus, an area important in appetite regulation. Relaxin-3 binds with high affinity to the recently discovered previously orphan G-protein-coupled receptor, GPCR135, which is expressed predominantly in the CNS, particularly in the hypothalamic paraventricular nucleus. Relaxin-3 also binds with high affinity to the LGR7 receptor expressed mainly in reproductive tissues, but also in the CNS. We hypothesised that relaxin-3 may play a novel role in appetite regulation. The aims of these studies were to examine the effect of intracerebroventricular (ICV) and intra-paraventricular nucleus (iPVN) administration of relaxin-3 on food intake in male Wistar rats, and to identify the receptor mediating these effects.

We report that ICV injections of human relaxin-3 (H3) (54 picomoles and 180 picomoles) in satiated male Wistar rats significantly increased food intake 1 hour post-administration [1.80 plus/minus 0.27 grams (54 picomoles H3) and 1.81 plus/minus 0.21 grams (180 picomoles H3) vs 0.96 plus/minus 0.16 grams (vehicle), p less than 0.05]. IntraPVN administration of relaxin-3 significantly increased 1 hour food intake in satiated rats [1.23 plus/minus 0.30 grams (18 picomoles H3) vs 0.34 plus/minus 0.16 grams (vehicle), p less than 0.05] and in the early dark phase [6.57 plus/minus 0.42 grams (18 picomoles H3) vs 4.43 plus/minus 0.32 grams (vehicle), p less than 0.05]. Behavioural analysis showed an increase in time spent feeding following iPVN relaxin-3 with no abnormal behaviours observed. Equimolar doses of human relaxin-2, which binds LGR7 receptor but not GPCR135, did not elicit any increase in feeding. These results suggest relaxin-3 may play a novel role in appetite control and that this orexigenic effect is mediated via the GPCR135 receptor.

* These authors contributed equally to the studies

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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