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

Abstract

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.

Centrally Administered Insulin-Like Growth Factor II Fails to Alter Pulsatile Growth Hormone Secretion or Food Intake

“…Third, CSF contains a mix ture of IGF binding proteins, primarily IGF-BP-2 [32], which theoretically could modulate the biological activity of IGF-II. While this latter factor was not controlled in the present experiments, it did not seem to interfere in earlier studies [24,29], Nevertheless, a role for IGF-II in feedback inhibition of GH secretion at a pituitary level is supported by most in vitro studies [20][21][22][23], although it should be noted that a few studies using either normal rat anterior pituitary cells [33] or human somatotrophinoma cells [34] failed to demonstrate an effect of IGF-II. In view of the larger body of evidence implicating IGF-I in GH-negative feed back, both at a pituitary [20][21][22][23]35, 36J and hypothalamic [35,37] level in vitro, as well as in vivo [29], it appears likely that the suppression of spontaneous pulses of GH release which we previously observed in vivo [24] was due primarily to the IGF-1 component of that preparation.…”

Localization of insulin-like growth factor-II mRNA in human pituitary adenomas

“…It has been reported that IGF-II inhibits GHRH-stimulated GH release from cultured rat anterior pituitary cells in a dose-dependent manner [6]. In vitro treatment of GH-secreting human pituitary adenomas with IGF-II had a significant inhibitory effect only in 2 out of 8 cases [15]. The presence of specific membrane receptors for IGF-I and IGF-II was demonstrated in primary cultures of human GH-producing pituitary adenomas [5] and in rat pituitary GH-secreting tumour cell lines [29].…”