Alpha melanocyte stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 receptor (MC3-R) and MC4-R and 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.
Objective: to investigate if adrenal and circulating AgRP is altered in Cushing's syndrome.
Methods: northern blot analysis was used to measure adrenal AgRP mRNA from 2 normal subjects and 2 patients with Cushing's syndrome. Plasma AgRP was measured in the 2 patients with Cushing's syndrome and 11 volunteers. RT-PCR was performed to determine the presence of the MC3R and MC4R in adrenal gland mRNA from a normal subject and a patient with Cushing's syndrome.
Results: Adrenal AgRP mRNA expression was significantly higher in the patients with Cushing's syndrome (0.10 plus/minus 0.01 arbitrary units) compared to controls (0.03 plus/minus 0.01 arbitrary units, p=0.02). Plasma AgRP in the patients with Cushing's syndrome (308 plus/minus 62 pg/ml) was higher than controls (209 plus/minus 17 pg/ml). There was a fall in plasma AgRP in patients with Cushing's syndrome following cure of their Cushing's syndrome by bilateral adrenalectomy and hydrocortisone replacement (168 plus/minus 16 pg/ml) to levels similar to controls. RT-PCR of adrenal gland mRNA from both a normal subject and from a patient with Cushing's syndrome demonstrated the presence of both the MC3R and MC4R.
Conclusion: adrenal and circulating AgRP is upregulated in Cushing's syndrome suggesting a novel inhibitory paracrine role in the human adrenal gland, which may be mediated via the MC3R or MC4R.
01 - 03 Nov 2004
Society for Endocrinology