1,25-dihydroxyvitamin D3-mediated transforming growth factor-beta release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies.
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.
Sterck
J G
JG
Department of Endocrinology, Vrije Universiteit, Amsterdam, Netherlands.
Klein-Nulend
J
J
Burger
E H
EH
Lips
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007018:Hypopituitarism / Q000378:metabolism*; D007085:Ilium / Q000166:cytology / Q000378:metabolism; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010907:Pituitary Hormones / Q000172:deficiency*; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D010907:Pituitary Hormones; D018167:Receptors, Calcitriol; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D002117:Calcitriol; D013936:Thymidine