BIOCHEMICAL CHARACTERISTICS OF HUMAN PITUITARY SOMATOTROPINOMAS WITH AND WITHOUT GSP MUTATIONS - IN-VITRO CELL-CULTURE STUDIES

Gsp oncogenes are present in about 40% of somatotropinomas. They resul t in excessive cAMP production and have been proposed to be the cause of increased GH secretion. We have used in vitro cell culture to compa re the biochemical characteristics of somatotropinomas with and withou t gsp oncogenes (gsp-positive and gps-negative tumors, respectively). Of 30 somatotropinomas examined, 10 proved to be gsp positive, as dete rmined by sequence analysis of DNA generated by the polymerase chain r eaction. The somatostatin anolog, octreotide, powerfully inhibited GH secretion by gsp-negative tumors. Five of 20 gsp-positive and 4 of 10 gsp-positive tumors failed to repond to GHRH, whereas stimulatory effe cts ranging from 37-500% increases in GH secretion occurred in the rem ainder. However, strong stimulation (>4-fold) occurred only in 5 of th e gsp-negative tumors. The basal phosphatidylinositol turnover rate wa s elevated in about 25% of gsp-negative somatotropinomas. These result s demonstrate similar and highly variable effects of GHRH on both type s of somatotropinoma, whereas the absence of gsp oncogenes is often as sociated with resistance to octreotide. The phosphatidylinositol turno ver data suggest that defects within this second messenger system may be present in a subset of somatotropinomas without gsp oncogenes.