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.
Adams
E F
EF
Department of Neurosurgery, University of Erlangen-Nürnberg, Germany.
Petersen
B
B
Lei
T
T
Buchfelder
M
M
Fahlbusch
R
R
D000172:Acromegaly / Q000378:metabolism; D000328:Adult; D001552:Benzazepines / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015290:Second Messenger Systems; D013777:Tetrazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001552:Benzazepines; D002147:Calmodulin; D009842:Oligopeptides; D010716:Phosphatidylinositols; D013777:Tetrazoles; C081455:L 692429; C041048:growth hormone releasing hexapeptide; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011493:Protein Kinase C; D010693:Phloretin