Widespread expression of Agouti-related protein (AGRP) in the chicken: a possible involvement of AGRP in regulating peripheral melanocortin systems in the chicken

Agouti-related protein (AGRP) is a naturally occurring antagonist of melano cortin action. It is expressed mainly in the arcuate nucleus where it plays an important role in the hypothalamic control of feeding and energy homeos tasis by antagonism of central melanocortin 4 receptors in mammals. Besides in the brain, the melanocortin 4 receptor is expressed in numerous periphe ral tissues in the chicken. To examine whether or not the peripheral melano cortin 4 receptor signaling could be regulated by AGRP, we cloned and local ized the expression of the AGRP gene in the chicken. The chicken AGRP gene was found to encode a 154 or 165 amino acid protein, depending on the usage of two alternative translation initiation sites. The coding sequence consi sted of three exons, like that of mammalian species. The C-terminal cystein e-rich region of the predicted AGRP displayed high levels of identity to ma mmalian counterparts (78-84%) and all 10 cysteine residues conferring funct ional conformation of AGRP were conserved; however, other regions showed ap parently no homology, suggesting that biological activities of AGRP are loc ated in its C-terminal region. RT-PCR analysis detected the AGRP mRNA in al l tissues examined: the brain, adrenal gland, heart, liver, spleen, gonads, kidney, uropygial gland, skeletal muscle and adipose tissues. Interestingl y, the skin also expressed the AGRP mRNA, where Agouti, another melanocorti n receptor antagonist regulating hair pigmentation, is expressed in rodents . Most of those AGRP-expressing tissues have been demonstrated to express m elanocortin 4 receptors and/or other subtypes of melanocortin receptor whos e mammalian counterparts can bind AGRP. These results imply the possibility that some peripheral melanocortin systems could be regulated by the functi onal interaction between melanocortins and AGRP at melanocortin receptors i n the chicken. (C) 2000 Elsevier Science B.V. All rights reserved.