17-BETA-ESTRADIOL INCREASES THE RECEPTOR NUMBER AND MODULATES THE ACTION OF 1,25-DIHYDROXYVITAMIN D-3 IN HUMAN OSTEOSARCOMA-DERIVED OSTEOBLAST-LIKE CELLS
M. Ishibe et al., 17-BETA-ESTRADIOL INCREASES THE RECEPTOR NUMBER AND MODULATES THE ACTION OF 1,25-DIHYDROXYVITAMIN D-3 IN HUMAN OSTEOSARCOMA-DERIVED OSTEOBLAST-LIKE CELLS, Calcified tissue international, 57(6), 1995, pp. 430-435
It is well known that 17 beta-estradiol (E(2)) and 1,25-dihydroxyvitam
in D-3 (1,25(OH)(2)D-3) have important roles in bone metabolism. This
study was undertaken to examine E(2) regulation of 1,25(OH)(2)D-3 rece
ptor (VDR) expression and the biological action of 1,25(OH)(2)D-3 in h
uman osteoblastlike cells. When human osteosarcoma-derived osteoblastl
ike cells were treated with varying concentrations of E(2), the VDR le
vels increased by up to 100% in a dose-dependent manner. VDR levels si
gnificantly increased at 10 nM E(2), and this increase plateaued at 10
0 nM E(2). E(2)-dependent increase of VDR was time dependent, plateaui
ng at 24 hours and was maintained for at least 48 hours in human osteo
blast-like cells. Scatchard analysis showed that E(2) increased the nu
mber of VDR (12.3 +/- 0.4 versus 26.5 +/- 0.3 fmol/mg protein; mean +/
- SE of three independent experiments) rather than the Kd (0.15 +/- 0.
02 versus 0.16 +/- 0.01 nM; mean +/- SE of three independent experimen
ts). Tamoxifen (50 nM), a specific competitor with E(2), completely ab
olished the E(2)-induced increase of VDR. The levels of VDR mRNA (4.5
kb) from the cells increased in a dose-dependent manner after E(2) tre
atment. With regard to the biological effects, E(2) increased by 10-25
% the inhibitory effect of 1,25(OH)(2)D-3 on cell growth. However, E(2
) did not increase the stimulation of alkaline phosphatase activity by
1,25(OH)(2)D3. The present study suggests that E, modulates the biolo
gical action of 1,25(OH)(2)D-3 through VDR levels in bone cells.