Effect of insulin-like growth factors on human foetal, adult normal and tumour pituitary function in tissue culture

Publisher Website
Google Scholar
Abstract
To determine the direct effects of insulin-like growth factors (IGFs) on hormone release by the human pituitary gland, human foetal, adult normal and tumour pituitary tissues were maintained in culture for 2 to 4 weeks and tested with acute (3 h) exposures to different preparations of IGF peptides. Adult normal pituitaries and adenomas were tested with a semipurified preparation of IGFs, free of immunoreactive insulin, containing IGF-I and IGF-II in a ratio of approximately 1:4. Human foetal pituitaries were tested with the semipurified IGFs as well as more purified preparations of IGF-I and IGF-II. Culture media were assayed for hGH, hPrl, hACTH and hLH using specific radioimmunoassays. Both foetal (n = 16 (No. of pituitaries), 33 (No. of observations)) and normal adult (n = 3, 16) human pituitaries cultures responded to the semipurified IGFs (2–25 ngEq/ml for foetal and 2–4 ngEq/ml for adult pituitaries) with a significant decrease in hGH release compared to basal (P < 0.01) whereas the GH-secreting pituitary tumours showed no effect when tested with from 2 to 25 ngEq/ml (n = 8, 129, ns). The effect of IGFs on human foetal somatotrope activity was dose-related for both the semipurified IGFs (2–25 ngEq/ml, n = 16, 33) and IGF-I or IGF-II (10–100 ng/ml; n = 3, 18). hPrl release was inhibited in the normal adult (n = 2, 12; P < 0.01) but not in the foetal (n = 2, 9; ns) pituitary cultures by 2–4 ngEq/ml of the semipurified IGFs, while the Prl-secreting pituitary tumour cultures showed variable responses to 3–4 ngEq/ml of the same IGFs preparation (a) suppression: n = 1, 14, P < 0.001; b) no effect: n = 3, 28, ns). hGH release was inhibited in one of the two mixed (GH- and Prl-secreting) tumours examined (n = 1, 10, P < 0.02) and unaffected in the other (n = 1, 14, ns), while hPrl release remained unchanged in both. The IGFs did not alter release of hLH or hACTH by either foetal or normal adult pituitaries. Conclusions: A semipurified preparation of IGFs directly inhibited hGH release by human foetal pituitaries and hGH and hPrl release by normal adult pituitaries but had no effect on hLH or hACTH secretion. Human foetal somatotropes responded to IGF-I and IGF-II in a similar dose-dependent manner suggesting that, like in the rat, both IGF peptides can have an inhibitory influence on GH secretion. GH- and/or Prl-secreting pituitary adenomas showed a predominant lack of responsiveness to the semipurified IGFs, suggesting that the sensitivity of somatotropes and lactotropes to an IGF inhibitory influence is often abnormal in the tumour state.