Alarin is a recently discovered splice variant of the galanin-like peptide (GALP) gene. Alarin is a
highly conserved 25 amino acid peptide which shares its first 5 amino acids with GALP, but lacks the
galanin receptor binding domain, suggesting that it mediates its biological effects through alternative
receptors. Alarin has been detected in the rodent hypothalamus. GALP has a well-characterised role in
the integration of energy and reproductive homeostasis.
Intracerebroventricular (ICV) alarin increases food intake and plasma luteinising hormone (LH) levels
in rats. Alarin stimulates the release of the orexigenic neuropeptide Y (NPY) and gonadotrophin
releasing hormone (GnRH) from hypothalamic explants, and GnRH release from an immortalised
GnRH releasing cell line. Pre-treatment with a GnRH antagonist blocked the alarin-induced increase
in plasma LH levels in vivo. These results suggest that ICV alarin activates the HPG axis via
hypothalamic GnRH release. My data also suggests that alarin does not bind to the known galanin
receptors.
The ventral tegmental area (VTA) is the origin of the mesolimbic dopamine pathway, which mediates
the rewarding properties of palatable food. Recent work suggests that the VTA reward pathway is
regulated by appetite-regulating signals including leptin and ghrelin. I have shown that intra-VTA
melanocortin receptor agonist administration inhibits food intake and administration of an antagonist
stimulates food intake in rats, suggesting that the melanocortin system may be involved in hedonic
regulation of appetite, in addition to its role in homeostatic regulation of appetite.
These studies have elucidated the biological effects of alarin in the regulation of appetite and the HPG
axis, and identified a role for the melanocortin system in regulating the central reward circuitry
modulating food intake. Further work is required to determine the receptor by which alarin mediates
its effect and its precise physiological function, and the physiological importance of the VTA
melanocortin system.