Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland

• Published in: Biochemical and biophysical research communications 2003-01, Vol.301 (1), p.102-107
• Main Authors: Dhillo, W.S., Small, C.J., Gardiner, J.V., Bewick, G.A., Whitworth, E.J., Jethwa, P.H., Seal, L.J., Ghatei, M.A., Hinson, J.P., Bloom, S.R.
• Format: Article
• Language: English
• Subjects: Adrenal; Adrenal Glands - metabolism; Agouti-Related Protein; AgRP; alpha-MSH - metabolism; Animals; Anti-Inflammatory Agents - metabolism; Corticosterone; Corticosterone - metabolism; Dexamethasone - metabolism; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; MC3-R; MC4-R; Paracrine Communication - physiology; Proteins - metabolism; Rat; Rats; Rats, Wistar; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Receptors, Corticotropin - antagonists & inhibitors; Receptors, Corticotropin - genetics; Receptors, Corticotropin - metabolism; α-MSH
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)02991-1

α-Melanocyte-stimulating-hormone (α-MSH) is an agonist at the melanocortin 3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R). α-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 α-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 α-MSH attenuated α-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 α-MSH-induced corticosterone secretion.