Alarin stimulates food intake and gonadotrophin release in male rats
Version of Record online: 25 MAY 2010
© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 161, Issue 3, pages 601–613, October 2010
How to Cite
Boughton, C., Patterson, M., Bewick, G., Tadross, J., Gardiner, J., Beale, K., Chaudery, F., Hunter, G., Busbridge, M., Leavy, E., Ghatei, M., Bloom, S. and Murphy, K. (2010), Alarin stimulates food intake and gonadotrophin release in male rats. British Journal of Pharmacology, 161: 601–613. doi: 10.1111/j.1476-5381.2010.00893.x
- Issue online: 3 SEP 2010
- Version of Record online: 25 MAY 2010
- Received3 September 2009Revised9 April 2010Accepted22 April 2010
- hypothalamo–pituitary–gonadal axis;
BACKGROUND AND PURPOSE Alarin is a recently discovered member of the galanin peptide family encoded by a splice variant of galanin-like peptide (GALP) mRNA. Galanin and GALP regulate energy homeostasis and reproduction. We therefore investigated the effects of alarin on food intake and gonadotrophin release.
EXPERIMENTAL APPROACH Alarin was administered into the third cerebral ventricle (i.c.v.) of rats, and food intake or circulating hormone levels were measured. The effect of alarin on the hypothalamo–pituitary–gonadal axis was investigated in vitro using hypothalamic and anterior pituitary explants, and immortalized cell lines. Receptor binding assays were used to determine whether alarin binds to galanin receptors.
KEY RESULTS The i.c.v. administration of alarin (30 nmol) to ad libitum fed male rats significantly increased acute food intake to 500%, and plasma luteinizing hormone (LH) levels to 170% of responses to saline. In vitro, 100 nM alarin stimulated neuropeptide Y (NPY) and gonadotrophin-releasing hormone (GnRH) release from hypothalamic explants from male rats, and 1000 nM alarin increased GnRH release from GT1-7 cells. In vivo, pretreatment with the GnRH receptor antagonist cetrorelix prevented the increase in plasma LH levels observed following i.c.v. alarin administration. Receptor binding studies confirmed alarin did not bind to any known galanin receptor, or compete with radiolabelled galanin for hypothalamic binding sites.
CONCLUSIONS AND IMPLICATIONS These results suggest alarin is a novel orexigenic peptide, and that it increases circulating LH levels via hypothalamic GnRH. Further work is required to identify the receptor(s) mediating the biological effects of alarin.