Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model.
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(beta-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+ 0.2 mmol) 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.
Department of Endocrine Surgery, Frenchay Hospital, Frenchay Park, Bristol, BS16 1LE, United Kingdom. christopher.wong@NBT.NHS.uk
C K M
CK
Wong
T
T
Lai
J M P
JM
Holly
M H
MH
Wheeler
C E H
CE
Stewart
J R
JR
Farndon
D000704:Analysis of Variance; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism / Q000601:surgery; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008297:Male; D010280:Parathyroid Glands / Q000166:cytology* / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II