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Human parathyroid cell proliferation in response to calcium, NPS R‐467, calcitriol and phosphate
Author(s) -
Roussanne MC.,
Lieberherr M.,
Souberbielle J. C.,
Sarfati E.,
Drüeke T.,
Bourdeau A.
Publication year - 2001
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2001.00809.x
Subject(s) - calcitriol , calcimimetic , parathyroid hormone , parathyroid chief cell , thymidine , endocrinology , medicine , cell growth , calcium , intracellular , chemistry , in vitro , calcium in biology , dna synthesis , cell culture , secondary hyperparathyroidism , biology , biochemistry , genetics
It remains uncertain how calcium, phosphate and calcitriol regulate parathyroid cell growth. The present study was aimed at examining possible direct effects of these modulators and of the calcimimetic NPS R‐467 on parathyroid cell growth in vitro . Cell proliferation was determined by [ 3 H]thymidine incorporation and cell cycle antigen Ki 67 expression in a parathyroid cell culture model derived from uraemic patients. The effect of NPS R‐467 on parathyroid hormone (PTH) secretion and intracellular [Ca 2+ ] i response was also examined. Increasing the [Ca 2+ ] in the medium from 0·5 to 1·7 mM increased DNA synthesis ( P < 0·005) and the number of Ki 67‐positive cells ( P < 0·005). However, NPS R‐467 (0·01–1 µM) inhibited 3 [H]thymidine incorporation by 35% in the presence of 0·5 mM [Ca 2+ ] e . Exposure of cells to Ca 2+ or NPS R‐467 led to a rapid increase of intracellular Ca 2+ , although the pattern of increase differed. Addition of calcitriol (10 −10 −10 −7 M) to the culture medium suppressed [ 3 H]thymidine incorporation dose‐dependently. Finally, high levels of phosphate (3·5 mM) in the medium led to a significant ( P < 0·05) increase in [ 3 H]thymidine incorporation. The observed stimulatory effect of Ca 2+ in the medium in vitro appears to be at variance with the inhibitory effect of calcimimetic NPS R‐467 in vitro . In an attempt to solve these apparent discrepancies, and based on the notion of a reduced calcium‐sensing receptor (CaR) expression in parathyroid tissues of uraemic patients, we hypothesize that Ca 2+ may regulate parathyroid cell proliferation via two different pathways, with predominant growth inhibition in cases of high CaR expression or activation, but prevailing stimulation of proliferation in cases of low CaR expression.