1,25-DIHYDROXYVITAMIN D-3-MEDIATED TRANSFORMING GROWTH-FACTOR-BETA RELEASE IS IMPAIRED IN CULTURED OSTEOBLASTS FROM PATIENTS WITH MULTIPLE PITUITARY-HORMONE DEFICIENCIES

Citation
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
Citations number
45
Categorie Soggetti
Endocrynology & Metabolism
ISSN journal
08840431
Volume
11
Issue
3
Year of publication
1996
Pages
367 - 376
Database
ISI
SICI code
0884-0431(1996)11:3<367:1DTGR>2.0.ZU;2-9
Abstract
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.