title: Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland.
abstract: alpha-Melanocyte-stimulating-hormone (alpha-MSH) is an agonist at the melanocortin 3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R). alpha-MSH stimulates corticosterone release from rat adrenal glomerulosa cells in vitro. Agouti-related protein (AgRP) an endogenous antagonist at the MC3-R and MC4-R, is expressed in the adrenal gland. We investigated the expression of the MC3-R and MC4-R and the role of AgRP in the adrenal gland. MC3-R and MC4-R expression was detected in rat adrenal gland using RT-PCR. The effect of AgRP on alpha-MSH-induced corticosterone release was investigated using dispersed rat adrenal glomerulosa cells. AgRP administered alone did not affect corticosterone release, but co-administration of AgRP and alpha-MSH attenuated alpha-MSH-induced corticosterone release. To investigate glucocorticoid feedback, adrenal AgRP expression was compared in rats treated with dexamethasone to controls. AgRP mRNA was increased in rats treated with dexamethasone treatment compared to controls. Our findings demonstrate that adrenal AgRP mRNA is regulated by glucocorticoids. AgRP acting via the MC3-R or MC4-R may have an inhibitory paracrine role, blocking alpha-MSH-induced corticosterone secretion.
authors.affiliation: Endocrine Unit, Faculty of Medicine, Imperial College, 6th Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
authors.forename: C J
authors.initials: CJ
authors.lastname: Small
authors.forename: J V
authors.initials: JV
authors.lastname: Gardiner
authors.forename: G A
authors.initials: GA
authors.lastname: Bewick
authors.forename: E J
authors.initials: EJ
authors.lastname: Whitworth
authors.forename: P H
authors.initials: PH
authors.lastname: Jethwa
authors.forename: L J
authors.initials: LJ
authors.lastname: Seal
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: J P
authors.initials: JP
authors.lastname: Hinson
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism*; D054369:Agouti-Related Protein; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D019899:Paracrine Communication / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism
chemical_list: C515198:AGRP protein, human; C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D000893:Anti-Inflammatory Agents; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH; D003907:Dexamethasone; D003345:Corticosterone