The activation of somatostatinergic receptors by either somatostatin-14 or cortistatin-17 often inhibits ACTH hypersecretion in patients with Cushing's disease

Object: Somatostatin (SS) is known to inhibit GH and insulin, while its effect on corticotrope secretion is controversial: inhibition of ACTH secretion by agonists activating somatostatinergic receptors (sst)-2 and sst-5 was reported in vitro. Cortistatin (CST) not only binds all sst receptor subtypes but also possesses central actions that are not shared by SS. Design: In nine patients with Cushing's disease (CD), ACTH, cortisol, GH, insulin, and glucose levels were studied during 120-min i.v. infusion of SS-14 (2.0 μg/kg per h), CST-17 (2.0 μg/kg per h) or saline. Results: Both SS or CST significantly affected the hypothalamic-pituitary-adrenal axis. Cortisol was decreased to the same extent by either SS or CST (P<0.05). Both SS and CST decreased ACTH, although statistical difference was reached only during CST (P<0.05). Analyzing the individual responses as Δareas under curve (ΔAUCs), a clear and consensual inhibition of ACTH and cortisol under either SS or CST was recorded in five out of nine patients. Both SS or CST inhibited (P < 0.05) insulin, thateven showed a rebound (P<0.01) at the end of infusion. GH was not modified by either peptide. Conclusion: SS and CST often display similar inhibitory effects on the HPA axis in CD. The activation of sst receptors by both peptides is followed in almost 50% of patients by a remarkable inhibition of ACTH and cortisol hypersecretion. These findings reinforce the view that sst receptors are involved in the control of the secretory activity of tumoral corticotropic cells.