1,25(OH)2D3 inhibits hormone secretion and proliferation but not functional dedifferentiation of cultured bovine parathyroid cells

Abstract

Increasing the extracellular Ca2+ concentration from 0.5 to 3.0 mM induced marked increments in cytoplasmic Ca2+ concentration (Ca2+i) and inhibition of parathyroid hormone (PTH) release of freshly isolated bovine parathyroid cells. 1,25-dihydroxycholecalciferol (1,24(OH)2D3; 0.1-100 ng/ml) did not affect (Ca2+i) and was also without acute effect on the secretion. During 4 days of monolayer culture, the parathyroid cells underwent significant increases in both number and size, and presence of 10-100 ng/ml 1,25(OH)2D3 almost completely inhibited the cell proliferation, whereas the hypertrophy was unaffected. One day of culture with 0.1-100 ng/ml 1,25(OH)2D3 was without effect on PTH release but after 4 days there was a dose-related reduction of secretion. At this time point and irrespective of the culture condition, PTH release was no longer suppressed by high extracellular Ca2+. Furthermore, Ca2+i increased little upon increments in the extracellular Ca2+ concentration as compared with freshly isolated cells. It is concluded that after prolonged exposure to 1,25(OH)2D3, PTH release is inhibited and, at high concentrations, the parathyroid cells cease to proliferate. However, 1,25(OH)2D3 does not affect the development of functional dedifferentiation of parathyroid cells during monolayer culture.