Sterck J G, Klein-Nulend J, Burger E H, Lips P
Department of Endocrinology, Vrije Universiteit, Amsterdam, Netherlands.
J Bone Miner Res. 1996 Mar;11(3):367-76. doi: 10.1002/jbmr.5650110310.
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 10(-8) M 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH)2D3 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)2D3 increased the release of both total and active transforming growth factor-beta (TGF-beta) 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-beta release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-beta release was not stimulated at all. One year of supplementation with 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)2D3 regarding cell proliferation and osteoblastic differentiation, which implicates a normal 1,25(OH)2D3-receptor function. In cells from controls and I-GHD, 1,25(OH)2D3 enhanced both total and active TGF-beta release. However, bone cells from M-PHD showed a deficient TGF-beta response to 1,25(OH)2D3. These results suggest that the regulation of TGF-beta production is a major paracrine factor involved in hypopituitarism.
为评估多重垂体激素缺乏症（M-PHD）患者和孤立性生长激素缺乏症（I-GHD）患者的成骨细胞功能，培养骨细胞并检测10⁻⁸ M 1,25-二羟基维生素D₃（1,25[OH]₂D₃）对细胞增殖、成骨细胞分化及局部旁分泌调节参数的影响。1,25(OH)₂D₃处理3天可增加碱性磷酸酶活性和骨钙素释放，但抑制患者及对照者所有细胞培养物中的[³H]胸腺嘧啶核苷掺入。此外，1,25(OH)₂D₃使对照者骨细胞中总转化生长因子-β（TGF-β）和活性TGF-β的释放分别增加4.9倍和3.2倍，使I-GHD患者骨细胞中总TGF-β和活性TGF-β的释放分别增加5.1倍和1.5倍。然而，在M-PHD患者的骨细胞中，总TGF-β释放的刺激作用明显低于对照者和I-GHD患者的细胞（1.3倍），且活性TGF-β释放根本未受刺激。补充人生长激素1年并未改善M-PHD患者骨细胞中这种TGF-β释放不足的情况。我们得出结论，I-GHD和M-PHD患者的培养骨细胞在细胞增殖和成骨细胞分化方面对1,25(OH)₂D₃表现出正常反应，这意味着1,25(OH)₂D₃受体功能正常。在对照者和I-GHD患者的细胞中，1,25(OH)₂D₃增强了总TGF-β和活性TGF-β的释放。然而，M-PHD患者的骨细胞对1,25(OH)₂D₃的TGF-β反应不足。这些结果表明，TGF-β产生的调节是垂体功能减退中涉及的主要旁分泌因子。
