Effects of insulin-like growth factor-II on growth hormone release from human somatotrophinoma cells in vitro.

Insulin-like growth factor-I (IGF-I) and IGF-II receptors have previously been demonstrated on membranes prepared from human somatotrophinomas. IGF-I has been shown to have a variable effect on GH secretion by these tumours in vitro. The effects of purified IGF-II on GH secretion have not been described. We have studied the direct actions of human recombinant IGF-II on GH release from eight somatotrophinomas cultured in vitro. Somatotrophinoma cells were cultured as monolayers at a density of 10(5) cells/0.5 ml. Treatment with IGF-II for 4 and 24 h resulted in discrete inhibitory effects on GH release from two tumours (tumour 5: 4 h, IGF-II 0.5 nmol/l; tumour 2; 24 h, IGF-II 1 nmol/l). Treatment with IGF-II for 24 h resulted in significant inhibitory effects on GH release from one tumour over a range of concentrations tested (IGF-II 0.5-10 nmol/l). Addition of human GH-releasing factor (hGRF) (1-44) (20 nmol/l) for 4 and 24 h resulted in stimulation of GH release by five tumours. Two tumours demonstrated significant inhibitory effects of IGF-II on GRF-stimulated GH release (tumour 2: 24 h, IGF-II 1-5 nmol/l; tumour 3; 4 h, IGF-II 5 nmol/l; 24 h, IGF-II 0.5-50 nmol/l). These data emphasize the heterogeneity of somatotrophinomas in terms of their response to modulators of GH secretion. IGF-II does not appear to have a modulatory role on GH release by most somatotrophinomas.