Effect of cyproheptadine, desmethylcyproheptadine, gamma-amino-butyric acid and sodium valproate on adrenocorticotrophin secretion by cultured pituitary tumour cells from three patients with Nelson's syndrome.

The effects of cyproheptadine, desmethylcyproheptadine, serotonin, gamma-amino-butyric acid (GABA) and sodium valproate were studied on ACTH secretion by cultured nonenzymatically dispersed pituitary tumour cells from three patients with Nelson's syndrome. Cyproheptadine (1-10 mumol/l) and desmethylcyproheptadine (1-10 mumol/l) suppressed ACTH secretion significantly (P less than 0.01), while serotonin (10 mumol/l) did not have a direct effect. Serotonin was also not able to reverse the (desmethyl)cyproheptadine-mediated inhibition of ACTH release. Sodium valproate and GABA did not exert a direct effect on hormone release by these cultured pituitary tumour cells. It is suggested that cyproheptadine-mediated inhibition of ACTH release in Nelson's syndrome might be effected by a direct non-serotonin-related effect on the pituitary tumour, while sodium valproate suppresses ACTH release by a suprahypophysial action.