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01-03-2006

Insulin-like Growth Factors (IGF) I and II Utilize Different Calcium Signaling Pathways in a Primary Human Parathyroid Cell Culture Model

Authors: C. K. M. Wong, PhD, T. Lai, BSci, J. M. P. Holly, PhD, M. H. Wheeler, MD, C. E. H. Stewart, PhD, J. R. Farndon, MD

Published in: World Journal of Surgery | Issue 3/2006

Abstract

Background

In most cell types, influx of calcium (Ca²⁺) induces a growth or secretory response. The opposite occurs in parathyroid (PTH), cells where there is an inverse relationship between intracellular Ca²⁺ concentration and PTH secretion. We have examined the effects of calcium channel and metabolism modulators on insulin-like growth factors (IGFs) in a parathyroid cell culture model.

Methods

Cell cultures were prepared from 9 patients undergoing operation for hyperparathyroidism. Following adhesion, the cells were transferred to serum-free medium and dosed with IGF I, II ± ethyleneglycol-bis(β-aminoethyl)-N, N, N′,N′-tetraacetic acid (EGTA), nifedipine, nickel, 2-aminoethoxy-diphenylborate (2-APB), or dantrolene. Proliferation (96 hours) was assessed by measuring tritiated thymidine incorporation and PTH release (1 and 3 hours) assayed by IRMA.

Results

Both IGF I and II increased DNA synthesis to 162.8% ± 10.6% (SEM) and 131.1% ± 7.7%, respectively (P < 0.05). EGTA at 0.2 mmol (ionized Ca²⁺ 0.2mmol) did not affect the response to both IGFs. EGTA at 2 mmol (ionized Ca²⁺ 0 mmol) reduced the DNA synthesis of IGF I and II to 29% and 26%, respectively (P < 0.05). Nifedipine and nickel (nonspecific Ca²⁺ channel blocker) were equally potent in negating the mitogenic effects of both IGFs. 2-APB (IP₃R blocker) reduced the basal DNA synthesis to 51.3% ± 8.4% but had no effect on either IGF. Dantrolene (ryanodine receptor blocker) negated IGF II induced mitogenisis (74.2% ± 6.7%) and partially inhibited IGF I mitogenesis (123% ± 6%) (P < 0.05). The rate of PTH secretion was greater after IGF II stimulation than after IGF I stimulation.

Conclusions

IGFs I and II induce mitogenesis by different calcium signaling pathways. These data suggest that parathyroid cells may utilize different calcium signaling pathways to distinguish growth factors and serum calcium changes.

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Title: Insulin-like Growth Factors (IGF) I and II Utilize Different Calcium Signaling Pathways in a Primary Human Parathyroid Cell Culture Model
Authors: C. K. M. Wong, PhD
T. Lai, BSci
J. M. P. Holly, PhD
M. H. Wheeler, MD
C. E. H. Stewart, PhD
J. R. Farndon, MD
Publication date: 01-03-2006
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 3/2006
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-005-0339-8

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Insulin-like Growth Factors (IGF) I and II Utilize Different Calcium Signaling Pathways in a Primary Human Parathyroid Cell Culture Model

Abstract

Background

Methods

Results

Conclusions

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Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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