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


METHODS
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 microg/kg per h), CST-17 (2.0 microg/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 areas under curve (AUCs), 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, that even showed a rebound (P < 0.01) at the end of infusion. GH was not modified by either peptide.


CONCLUSIONS
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.
Giordano
R
R
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, 10126 Turin, Italy.
Picu
A
A
Bonelli
L
L
Broglio
F
F
Prodam
F
F
Grottoli
S
S
Muccioli
G
G
Ghigo
E
E
Arvat
E
E
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000009:adverse effects / Q000494:pharmacology*; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000009:adverse effects / Q000494:pharmacology*
C105172:CORT protein, human; D002352:Carrier Proteins; D007328:Insulin; D009479:Neuropeptides; D017481:Receptors, Somatostatin; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone