Alarin stimulates food intake and gonadotrophin release in male rats.
OBJECTIVE
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.


METHODS
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.


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
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.
Boughton
C K
CK
Department of Investigative Medicine, Imperial College London, Commonwealth Building, Du Cane Road, London, UK.
Patterson
M
M
Bewick
G A
GA
Tadross
J A
JA
Gardiner
J V
JV
Beale
K E L
KE
Chaudery
F
F
Hunter
G
G
Busbridge
M
M
Leavy
E M
EM
Ghatei
M A
MA
Bloom
S R
SR
Murphy
K G
KG
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D004435:Eating / Q000187:drug effects*; D044089:Galanin-Like Peptide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D044089:Galanin-Like Peptide; D006062:Gonadotropins; D009478:Neuropeptide Y; D044088:Receptors, Galanin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; C062876:cetrorelix