EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON GROWTH-HORMONE AND PROLACTIN SECRETION AND CELL-PROLIFERATION OF HUMAN SOMATOTROPHINOMAS AND PROLACTINOMAS IN-VITRO

OBJECTIVE IGF-I inhibits GH secretion from normal and some tumorous pi tuitary tissue, and has been shown to be mitogenic for gonadotrophinom a cells in vitro. It is not known whether IGF-I affects somatotrophino ma cellular proliferation or the secretion of other hormones, such as PRL and a-subunit, which are often co-secreted by these tumours. We ha ve therefore examined the effects of IGF-I on proliferation and hormon al secretion of human somatotrophinomas and prolactinomas in vitro. DE SIGN Pituitary adenoma tissue was dispersed to single cells in monolay er culture. The effects of 100 nM IGF-I on GH, PRL and alpha-subunit s ecretion were determined over 4-hour and over 4-day periods, and a 4-d ay dose-response study using 1-100 nM IGF-I was performed on two tumou rs. Adenoma cell S-phase proliferation was determined after bromodeoxy uridine incorporation for 1 hour after 4 days, using a double immunost aining method. RESULTS Over 4 hours, 100 nM IGF-I had no effect on GH, PRL or alpha-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF- I reduced GH secretion in 5/8 somatotrophinomas (range 17-84%, P < 0.0 5) compared to controls, with tumours responding to IGF-I having lower basal serum and in-vitro GH levels than tumours unaffected by IGF-I ( P < 0.05). There was no effect on a-subunit secretion in any of the th ree tumours studied. PRL cosecretion was increased in 3/5 somatotrophi nomas compared to control (20, 30 and 37%, P < 0.05), with tumours res ponding to IGF-I being associated with lower basal serum and in-vitro PRL levels than those tumours unaffected by IGF-I. IGF-I also increase d PRL secretion in 2/2 prolactinomas (27 and 32%, P < 0.05) compared w ith control. GH was inhibited and PRL secretion was stimulated by 1 an d 10 nM IGF-I in the two dose-response studies. The proliferative labe lling index did not exceed 1.9% in any tumour and no proliferative eff ect was found with 100 nM IGF-I in any somatotrophinoma. CONCLUSION IG F-I inhibited tumorous GH in 62% and stimulated PRL secretion in 71% o f tumours over 4 days, without affecting alpha-subunit secretion or be ing mitogenic for somatotrophinoma cells in vitro. No hormonal effects were observed over short (4-hour) incubations. IGF-I may be a newly r ecognized factor directly stimulating tumorous PRL secretion.