A suppressive effect of dexamethasone (DEX) on adrenocorticotropin (ACTH) response to vasoactive intestinal peptide (VIP) in Cushing's disease: a parallel modulation by DEX of ACTH responses to VIP and corticotropin-releasing hormone.
We have previously reported and confirmed that vasoactive intestinal peptide (VIP) is a significant stimulator of ACTH and cortisol secretion in at least some patients with Cushing's disease. We have also found that the hormonal responses to corticotropin-releasing hormone (CRH) in VIP-responsive patients with Cushing's disease were higher than those in VIP non-responders, which suggested a linkage between the actions of CRH and VIP in this disorder. Therefore, in the present study we examined whether this linkage also exists after glucocorticoid treatment by testing the effect of dexamethasone (DEX) pretreatment (1.0 mg, intravenous bolus, 60 min before) on ACTH and cortisol responses to CRH (100 microg, i.v. bolus) and VIP (100 microg, i.v. bolus) in 7 patients with Cushing's disease who were responsive to both neuropeptides while under no DEX pretreatment. The results were that in 5 patients, DEX was able to significantly suppress the ACTH and cortisol responses to both CRH and VIP, and in the remaining 2 patients, DEX did not significantly affect the action of either CRH or VIP. This study is the first to demonstrate the parallel inhibition by DEX of ACTH and cortisol responses to CRH and VIP in Cushing's disease. Although the possibility cannot be excluded that VIP may act on CRH receptors in corticotropinomas as a partial agonist, it seems more likely that specific receptors for CRH and VIP, respectively, may concurrently express in substantial quantity in those corticotropinomas that are responsive to both neuropeptides.
Watanobe
H
H
Third Department of Internal Medicine, Hirosaki University School of Medicine, Aomori, Japan.
Tamura
T
T
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D003480:Cushing Syndrome / Q000188:drug therapy*; D003907:Dexamethasone / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*
D000893:Anti-Inflammatory Agents; D014660:Vasoactive Intestinal Peptide; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone