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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

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An Erratum to this article was published on 28 April 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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Authors and Affiliations

  1. Department of Endocrine Surgery, Frenchay Hospital, Frenchay Park, Bristol, BS16 1LE, United Kingdom

    C. K. M. Wong PhD, T. Lai BSci, C. E. H. Stewart PhD & J. R. Farndon MD

  2. Department of Exercise and Sport Science, MMU Cheshire, Hassall Road, Alsager, Cheshire, ST7 2HL, United Kingdom

    M. H. Wheeler MD

  3. Division of Surgery, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol, BS2 8HW, United Kingdom

    J. M. P. Holly PhD

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  1. C. K. M. Wong PhD
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  2. T. Lai BSci
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  3. J. M. P. Holly PhD
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  5. C. E. H. Stewart PhD
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  6. J. R. Farndon MD
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Correspondence to C. K. M. Wong PhD.

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An erratum to this article is available at http://dx.doi.org/10.1007/s00268-006-0264-5.

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Wong, C.K.M., Lai, T., Holly, J.M.P. et al. Insulin-like Growth Factors (IGF) I and II Utilize Different Calcium Signaling Pathways in a Primary Human Parathyroid Cell Culture Model. World J. Surg. 30, 333–345 (2006). https://doi.org/10.1007/s00268-005-0339-8

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