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Effects of insulin‐like growth factor‐I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro
Author(s) -
Atkin S. L.,
Landolt A. M.,
Fay P.,
Jeffreys R. V.,
Hipkin L.,
White M. C.
Publication year - 1994
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1994.tb02582.x
Subject(s) - medicine , endocrinology , prolactin , secretion , biology , somatomedin , growth factor , adenoma , cell growth , pituitary gland , hormone , prolactin cell , in vitro , insulin like growth factor , cell culture , receptor , growth hormone , biochemistry , genetics
Summary OBJECTIVE IGF‐I inhibits GH secretion from normal and some tumorous pituitary tissue, and has been shown to be mitogenic for gonadotrophinoma cells in vitro. It is not known whether IGF‐l affects somatotrophinoma cellular proliferation or the secretion of other hormones, such as PRL and α‐subunit, which are often co‐secreted by these tumours. We have therefore examined the effects of IGF‐l on proliferation and hormonal secretion of human somatotrophinomas and prolactinomas in vitro. DESIGN Pituitary adenoma tissue was dispersed to single cells in monolayer culture. The effects of 100 nw IGF‐I on GH, PRL and α‐subunit secretion were determined over 4‐hour and over 4‐day periods, and a 4‐day dose‐response study using 1–100 nM IGF‐I was performed on two tumours. Adenoma cell S‐phase proliferation was determined after bromodeoxyuridine Incorporation for 1 hour after 4 days, using a double immunostaining method. RESULTS Over 4 hours, 100 nw IGF‐I had no effect on GH, PRL or α‐subunit secretion in 7 tumours. Over 4 days, 100 nw IGF‐I reduced GH secretion In 518 somatotrophinomas (range 17–84%, P < 0·05) 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 α‐subunit secretion in any of the three tumours studied. PRL co‐secretion was increased In 315 somatotrophinomas compared to control (20, 30 and 37%, P < 0·05), with tumours responding to IGF‐I being associated with lower basal serum and in‐vitro PRL levels than those tumours unaffected by IGF‐I. IGF‐I also increased PRL secretion in 2/2 prolactinomas (27 and 32%, P < 0·05) compared with control. GH was inhibited and PRL secretion was stimulated by 1 and 10 nw IGF‐I in the two dose‐response studies. The proliferative labelling index did not exceed 1·9% in any tumour and no proliferative effect was found with 100 nw IGF‐I in any somatotrophinoma. CONCLUSION IGF‐I inhibited tumorous GH in 62% and stimulated PRL secretion in 71 % of tumours over 4 days, without affecting α‐subunit secretion or being mitogenic for somatotrophinoma cells in vitro. No hormonal effects were observed over short (4‐hour) incubations. IGF‐I may be a newly recognized factor directly stimulating tumorous PRL secretion.