1,25-DIHYDROXYVITAMIN D-3-MEDIATED TRANSFORMING GROWTH-FACTOR-BETA RELEASE IS IMPAIRED IN CULTURED OSTEOBLASTS FROM PATIENTS WITH MULTIPLE PITUITARY-HORMONE DEFICIENCIES
Jgh. Sterck et al., 1,25-DIHYDROXYVITAMIN D-3-MEDIATED TRANSFORMING GROWTH-FACTOR-BETA RELEASE IS IMPAIRED IN CULTURED OSTEOBLASTS FROM PATIENTS WITH MULTIPLE PITUITARY-HORMONE DEFICIENCIES, Journal of bone and mineral research, 11(3), 1996, pp. 367-376
To evaluate the osteoblastic function in patients with multiple pituit
ary hormone deficiencies (M-PHD) and with isolated growth hormone defi
ciency (I-GHD), bone cells were cultured and the effects of 10(-8) M 1
,25-dihydroxyvitamin D-3 (1,25[OH]D-2(3)) on parameters of cell prolif
eration, osteoblastic differentiation, and local paracrine regulation
were measured. Three days of 1,25(OH)(2)D-3 treatment increased alkali
ne phosphatase activity and osteocalcin release but inhibited [H-3]thy
midine incorporation in all cell cultures from patients as well as fro
m controls. In addition, 1,25(OH)(2)D-3 increased the release of both
total and active transforming growth factor-beta (TGF-beta) in bone ce
lls from controls by, respectively, 4.9- and 3.2-fold and in bone cell
s from I-GHD by 5.1- and 1.5-fold, respectively. However, in bone cell
s from M-PHD, the stimulation of total TGF-beta release was significan
tly lower (1.3-fold) than in control and I-GHD cells, and active TGF-b
eta release was not stimulated at all. One year of supplementation wit
h human growth hormone did not improve this deficient TGF-beta release
in bone cells from M-PHD. We conclude that cultured bone cells from I
-GHD and M-PHD show a normal response to 1,25(OH)(2)D-3 regarding cell
proliferation and osteoblastic differentiation, which implicates a no
rmal 1,25(OH)(2)D-3-receptor function. In cells from controls and I-GH
D, 1,25(OH)(2)D-3 enhanced both total and active TGF-beta release. How
ever, bone cells from M-PHD showed a deficient TGF-beta response to 1,
25(OH)(2)D-3. These results suggest that the regulation of TGF-beta pr
oduction is a major paracrine factor involved in hypopituitarism.