title: Agouti related protein (AgRP) is upregulated in Cushing's syndrome.
abstract: Alpha melanocyte-stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 (MC3-R) and melanocortin 4 (MC4-R) receptors. Alpha-MSH stimulates corticosterone release from rat and human adrenal cells. Patients with Cushing's syndrome have elevated levels of serum alpha-MSH. Agouti related protein (AgRP) is an endogenous antagonist at the MC3-R and MC4-R and is expressed in the rat adrenal cortex. AgRP antagonises alpha-MSH-induced corticosterone release from rat and bovine adrenal cells. This suggests that AgRP may have an inhibitory paracrine role in the adrenal gland. We measured adrenal AgRP mRNA expression and circulating AgRP in 2 patients with Cushing's syndrome and controls. Adrenal AgRP mRNA expression and plasma AgRP were higher in the patients with Cushing's syndrome compared to controls. Plasma AgRP in the patients with Cushing's syndrome following bilateral adrenalectomy and hydrocortisone replacement were similar to the levels seen in controls. Our results suggest that AgRP may have a novel inhibitory paracrine role in the human adrenal gland.
authors.affiliation: Department of Metabolic Medicine, Faculty of Medicine, Imperial College, 6th Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
authors.forename: J V
authors.initials: JV
authors.lastname: Gardiner
authors.forename: L
authors.initials: L
authors.lastname: Castle
authors.forename: G A
authors.initials: GA
authors.lastname: Bewick
authors.forename: K L
authors.initials: KL
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Meeran
authors.forename: J F
authors.initials: JF
authors.lastname: Todd
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D054369:Agouti-Related Protein; D003480:Cushing Syndrome / Q000235:genetics*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C515198:AGRP protein, human; C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4