1,25-Dihydroxyvitamin D3 stimulates growth and inhibits calcitonin secretion in a human C cell carcinoma cell line.

1,25-Dihydroxyvitamin D3 (1,25D3), calcitonin (CT) and parathyroid hormone are the major calcium-regulating hormones. In addition, 1,25D3 has been reported to be a modulator of cell growth and differentiation in many tissues. Recently, a suppressive effect of 1,25D3 on CT secretion and synthesis in C cells was demonstrated in vivo and also in vitro, but there are no data about its effects on thyroid C cell growth. We investigated the effects of 1,25D3 on basal and stimulated CT secretion and on [3H]thymidine incorporation, using a human medullary thyroid carcinoma cell line (TT cells). After a 4-day exposure to 1,25D3, TT cells showed a dose-dependent inhibition of basal CT secretion (64% of the value for the control group at 100 nM 1,25D3). Calcium (3 mM) plus K+ (50 mM) greatly increased CT secretion in both the control and vitamin D-treated groups. However, in the cells preincubated with 1,25D3 the stimulated CT levels were less than observed in controls. A dose-dependent increase in [3H]thymidine incorporation (200% of the value for the control group at 100 nM 1,25D3) and in cell number (150% of the value for the control group at 100 nM 1,25D3 after 72 h) was observed in the groups treated with 1,25D3. 24,25D3 had no effect on CT secretion or cell growth compared to the control group. These data show that 1,25D3 decreased basal and Ca(2+)-stimulated CT secretion, a specialized function of these cells, and stimulated their growth. Hence, in contrast to its effects on other cell lines, 1,25D3 appears to induce a dedifferentiation on TT cells.