Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro

Stephen Atkin, A. M. Landolt, P. Foy, R. V. Jeffreys, L. Hipkin, M. C. White

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Abstract

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-I 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-I 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 nM 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 nM IGF-I had no effect on GH, PRL or α-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 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 3/5 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 nM 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 nM 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.

Original languageEnglish
Pages (from-to)503-509
Number of pages7
JournalClinical Endocrinology
Volume41
Issue number4
Publication statusPublished - 1994
Externally publishedYes

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Prolactinoma
Insulin-Like Growth Factor I
Prolactin
Growth Hormone
Cell Proliferation
Neoplasms
In Vitro Techniques
Pituitary Neoplasms
Bromodeoxyuridine

ASJC Scopus subject areas

  • Endocrinology

Cite this

Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro. / Atkin, Stephen; Landolt, A. M.; Foy, P.; Jeffreys, R. V.; Hipkin, L.; White, M. C.

In: Clinical Endocrinology, Vol. 41, No. 4, 1994, p. 503-509.

Research output: Contribution to journalArticle

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title = "Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro",
abstract = "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-I 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-I 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 nM 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 nM IGF-I had no effect on GH, PRL or α-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 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 3/5 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 nM 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 nM 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.",
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T1 - Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro

AU - Atkin, Stephen

AU - Landolt, A. M.

AU - Foy, P.

AU - Jeffreys, R. V.

AU - Hipkin, L.

AU - White, M. C.

PY - 1994

Y1 - 1994

N2 - 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-I 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-I 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 nM 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 nM IGF-I had no effect on GH, PRL or α-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 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 3/5 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 nM 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 nM 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.

AB - 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-I 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-I 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 nM 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 nM IGF-I had no effect on GH, PRL or α-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 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 3/5 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 nM 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 nM 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.

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