The growth hormone secretagogue, L-692,429, induces phosphatidylinositol hydrolysis and hormone secretion by human pituitary tumors

L-692,429 is a non-peptidyl GH secretagogue. We examined the effects of L-692,429 on cultured human pituitary tumors removed from patients with acromegaly. Dose-dependent stimulation of GH secretion was observed, with 1 mumol/L leading to 2 or 3-fold increases. Prolactin (PRL) secretion by a mixed somatotrophic-lactotrophic tumor was also stimulated. The effects of L-692,429 were abolished by phloretin and W7 but not Rp-cAMPS. Rate of phosphatidylinositol turnover was markedly increased up to 3-fold by L-692,429. These results show that L-692,429 increases hormone secretion by human pituitary cells via a protein kinase C and Ca2+ dependent mechanism.