1,25-Dihydroxyvitamin D3—mediated transforming growth factor-β release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies
✍ Scribed by Jozien G. H. Sterck; Jenneke Klein-Nulend; Elisabeth H. Burger; Paul Lips
- Publisher
- American Society for Bone and Mineral Research
- Year
- 2009
- Tongue
- English
- Weight
- 801 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0884-0431
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✦ Synopsis
To evaluate the osteoblastic function in patients with multiple pituitary hormone deficiencies (M-PHD) and with isolated growth hormone deficiency (I-GHD), bone cells were cultured and the effects of lo-' M 1,25-dihydroxyvitamin D, (1,25 [OH],D,) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH),D, treatment increased alkaline phosphatase activity and osteocalcin release but inhibited [3H]thymidine incorporation in all cell cultures from patients as well as from controls. In addition, 1,25(OH),D, increased the release of both total and active transforming growth factor-p (TGF-P) in bone cells from controls by, respectively, 4.9-and 3.2-fold and in bone cells from I-GHD by 5.1-and 1.5-fold, respectively. However, in bone cells from M-PHD, the stimulation of total TGF-P release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-P release was not stimulated at all. One year of supplementation with human growth hormone did not improve this deficient TGF-P 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),D, regarding cell proliferation and osteoblastic differentiation, which implicates a normal 1,25(0H),D,-receptor function. In cells from controls and I-GHD, 1,25(OH),D, enhanced both total and active TGF-P release. However, bone cells from M-PHD showed a deficient TGF-P response to 1,25(OH),D,. These results suggest that the regulation of TGF-P production is a major paracrine factor involved in hypopituitarism. (J