Alarin stimulates food intake and the hypothalamo-pituitarygonadal axis in male rats
Charlotte Boughton, Michael Patterson, Gavin Bewick, John Tadross, James Gardiner, Faizan Chaudery, George Hunter, Mohammad Ghatei, Stephen Bloom & Kevin Murphy
Alarin is the most recently discovered member of the galanin peptide family, and is encoded by a splice variant of galanin-like peptide (GALP) mRNA. Galanin and GALP are known to regulate energy homeostasis and reproduction. Galanin is thought to mediate its effects via the three-galanin receptors. GALP also binds to these known galanin receptors, but evidence suggests that it may also act via an as yet unknown GALP specific receptor. The role of alarin in energy homeostasis and reproduction is currently unknown. The objective of these studies was thus to determine the effects of alarin on food intake and the hypothalamo-pituitarygonadal axis.
Intracerebroventricular (ICV) administration of alarin (30 nmol) to unanaesthetised ad libitum fed male rats significantly increased food intake 1 h after injection (01 h food intake/g: saline 0.60±0.28, alarin 30 nmol 3.06±0.55, P<0.01). ICV administration of alarin (6 nmol) to unanaesthetised adult male rats significantly increased plasma LH levels 30 min after injection (plasma LH ng/ml; saline 0.7±0.1, 6 nmol alarin 1.0±0.1, P<0.05). In vitro, alarin stimulated Neuropeptide Y (NPY) and GnRH release from hypothalamic explants from male rats, and GnRH release from GT1-7 cells. In vivo, pre-treatment with the GnRH receptor antagonist cetrorelix blocked the alarin-induced stimulation of plasma LH levels in unanaesthetised adult male rats. Receptor binding studies confirmed that alarin does not bind to galanin receptors 1 or 2, and demonstrated that alarin does not compete with radiolabelled galanin for hypothalamic binding sites. These results suggest that alarin is a novel orexigenic peptide, and that it stimulates the HPG axis via hypothalamic GnRH. Further work is now required to determine the receptor that mediates the biological effects of alarin.