Alarin 6-25Cys antagonizes alarin-specific effects on food intake and luteinizing hormone secretion

Previous data from our labs and from others have demonstrated that intracerebroventricular (ICV) injection of alarin has orexigenic activity and significantly increases plasma luteinizing hormone (LH) secretion in a gonadotropin-releasing hormone (GnRH) dependent manner. The purpose of the current experiments was to determine if the amino acids at the amino-terminal end of the alarin peptide are critical for alarin's effects on reproductive and feeding systems. First, we injected male mice ICV with full-length alarin (Ala1-25) or peptide fragments missing residues at the amino-terminal end (Ala3-25 or Ala6-25 Cys). Neither peptide fragment alone, significantly increased food intake in male mice compared to controls. Second, ICV injection of Ala1-25, but not Ala3-25, significantly (p < 0.01) increased GnRH-mediated LH secretion. Surprisingly, Ala6-25 Cys significantly (p < 0.05) inhibited plasma LH secretion and inhibited Ala1-25 actions. In conclusion, elimination of the first five amino acids of alarin not only abolishes the biological activity of alarin, but becomes an antagonist to alarin-specific effects. Furthermore, Ala6-25 Cys seems to act as a specific antagonist to putative alarin receptors and therefore may be an important tool in identifying alarin-specific receptors.