AJP - Endocrinology and Metabolism, Vol 270, Issue 4 E654-E660, Copyright © 1996 by American Physiological Society
Downregulation of the PTH/PTHrP receptor by vitamin D3 in the osteoblast-like ROS 17/2.8 cells
L. Y. Xie, A. Leung, G. V. Segre, I. Yamamoto and A. B. Abou-Samra
Endocrine Unit, Massachusetts General Hospital, Boston 02114, USA.
Effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the expression of the
parathyroid hormone (PTH)/PTH-related peptide (rP) receptor protein and
mRNA in ROS 17/2.8 cells were studied. Treatment of ROS 17/2.8 cells with
1,25(OH)2D3 caused time- and dose-dependent suppression of PTH/PTHrP
receptor number and immunoreactivity. The effects required more than 24 h
incubation with 1,25(OH)2D3 and were maximal by 72 h. The cells did not
recover their PTH/PTHrP receptors even after 4 days of treatment with
control medium. Treatment with low concentrations of 1,25(OH)2D3 (0.1 M)
dramatically decreased the PTH/PTHrP receptor mRNA levels, which were
maximal after 24 h of incubation. The half-life of the PTH/PTHrP receptor
transcript, 6-8 h, was similar in control and 1,25(OH)2D3-treated cells,
suggesting that 1,25(OH)2D3 acts in controlling transcription of the
PTH/PTHrP receptor gene but does not change the degradation rate of the
PTH/PTHrP receptor transcripts. These data indicate that 1,25(OH)2D3 has a
potent inhibitory effect on the expression of the PTH/PTHrP receptor
protein and mRNA in ROS 17/2.8 cells.
