Heterologous up-regulation of the 1,25-dihydroxyvitamin D3 receptor by parathyroid hormone (PTH) and PTH-like peptide in osteoblast-like cells

Pols, Huibert A. P.; Leeuwen, Johannes P.T.M. van; Schilte, J.P.; Visser, Theo J.; Birkenhäger, J. C.

doi:10.1016/s0006-291x(88)80883-0

Cited by 40 publications

(17 citation statements)

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“…Recently, it has been reported that pretreatment of UMR 106 cells with EGF inhibits the cellular cAMP response to PTH [20]. In these cells the PTH-stimulated 1,25(OH)zD 3 binding is preceded by an increase in cAMP production [11]. The present study shows that inhibition of PTH-stimulated cAMP production is accompanied by an attenuation of the PTHstimulated increase of 1,25(OH)2D 3 binding sites (Fig.…”

Section: Discussionsupporting

confidence: 70%

“…Recently, we have shown that PTH dose-dependently stimulates 1,25(OH)zD3 binding [11]. As depicted in Figure 3, 24 h preincubation with EGF resulted in a dose-dependent reduction of the stimulation of 1,25(OH)2D 3 binding by PTH.…”

Section: Resultsmentioning

confidence: 72%

“…The stimulation of 1,25(OH)2D 3 binding by PTH is preceded by a stimulation of cAMP production [11]. As presented in Figure 3, inhibition of PTH-stimulated 1,25(OH)2D3 binding by EGF is accompanied by an inhibition of PTH-stimulated cAMP production.…”

Section: Resultsmentioning

confidence: 79%

“…For instance, preincubation of osteoblast-like cells with 1,25(OH)2D 3 attenuates the stimulation of cAMP production by PTH [7][8][9][10]. Furthermore, we have recently reported that PTH and PTHrelated protein cause heterologous up-regulation of the 1,25(OH)2D3 receptor [11].It has been shown that besides these two well-known calciotrophic hormones, growth factors and cytokines also affect bone cell metabolism. One of these polypeptide growth factors is epidermal growth factor (EGF) which has been shown to stimulate bone resorption in vitro [12,13].…”

mentioning

confidence: 99%

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Modulation by epidermal growth factor of the basal 1,25(OH)2D3 receptor level and the heterologous up-regulation of the 1,25(OH)2D3 receptor in clonal osteoblast-like cells

et al. 1991

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Summary. The effects of epidermal growth factor (EGF) on basal 1,25-dihydroxyvitamin D 3 (1,25-(OH)2D3) receptor level and on parathyroid hormone (PTH)-induced 1,25-(OH)2D3 receptor up-regulation were studied in the phenotypically osteoblastic cell line UMR 106. EGF in concentrations exceeding 0.1 ng/ml reduced the number of 1,25(OH)2D 3 binding sites without changing the binding affinity. Maximal reduction was 30% at about 1 ng/ml. This reduction was independent of a change in cAMP content. EGF dose-dependently attenuated both PTH-induced 1,25(OH)2D 3 receptor up-regulation and PTH-stimulated cAMP production, without an effect on the EDso of the PTH effects. For both PTH responses the IC5o and the maximal effective dose were similar, 0.1 ng/ml and 1 ng/ml EGF, respectively. Reduction was first seen at 0.01 ng/ml EGF. At this concentration, EGF reduced PTH-stimulated 1,25-(OH)2D 3 receptor binding without an inhibition of the cAMP response. Time-course studies with 1 ng/ml EGF revealed that at 2 h preincubation EGF reduced the heterologous upregulation by PTH, and maximal inhibition was seen after 4 h. In contrast, PTH-stimulated cAMP production was just significantly inhibited only after 6 h, with 60% inhibition after 24 h preincubation. The effects of prostaglandin E 2 and forskolin on both 1,25(OH)eD3 binding and cAMP production were inhibited in a similar fashion. On the other hand, dibutyryl cAMP-and 3-isobutyl-l-methylxanthinestimulated 1,25(OH)2D3 binding were not affected by EGF. Taken together, our results demonstrate that EGF reduces both the basal number of 1,25(OH)2D3 binding sites and the heterologous up-regulation of the 1,25(OH)2D 3 receptor. The current data suggest that EGF reduces heterologous upregulation of the 1,25(OH)2D3 receptor independent of as well as dependent on the cAMP messenger system. The EGF effect is not primarily located at the PTH receptor, at cAMP phosphodiesterase, or at protein kinase A level.Key words: EGF-1,25(OH)zD 3 binding -PTH -Osteoblast cell line.1,25-Dihydroxyvitamin D 3 (1,25(OH)2D3) and parathyroid hormone (PTH) play an important role in calcium homeostasis. One of the target tissues for 1,25(OH)2D3 and PTH is bone. For both hormones the receptors in bone are located on the osteoblast [1][2][3][4]. From in vitro as well as in vivo studies, evidence has been obtained indicating that 1,25 (OH)2D 3 and PTH act in an interrelated fashion [5,6]. Also at the level of the osteoblast, interactions between 1,25(OH)2D 3 and PTH have been reported. For instance, preincubation of osteoblast-like cells with 1,25(OH)2D 3 attenuates the stimulation of cAMP production by PTH [7][8][9][10]. Furthermore, we have recently reported that PTH and PTHrelated protein cause heterologous up-regulation of the 1,25(OH)2D3 receptor [11].It has been shown that besides these two well-known calciotrophic hormones, growth factors and cytokines also affect bone cell metabolism. One of these polypeptide growth factors is epidermal growth factor (EGF) which has been shown to stimulate bone resorpti...

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Section: Discussionsupporting

confidence: 70%

Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 79%

mentioning

confidence: 99%

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Modulation by epidermal growth factor of the basal 1,25(OH)2D3 receptor level and the heterologous up-regulation of the 1,25(OH)2D3 receptor in clonal osteoblast-like cells

et al. 1991

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“…Previous investigations into PTH-mediated regulation of VDR expression yielded mixed results. A PTH-mediated increase of VDR and VDR mRNA was reported in osteoblastlike UMR-106 cells (20,21), whereas a PTH-mediated decrease in VDR and its transcript was reported in ROS 17͞2.8 osteoblast cells (22). In vivo, osmotic PTH administration to rats nearly doubled renal VDR levels (23).…”

mentioning

confidence: 98%

Parathyroid hormone decreases renal vitamin D receptor expressionin vivo

Healy

Vanhooke²,

Prahl³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The vitamin D receptor (VDR) is a nuclear transcription factor responsible for mediating the biological activities of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Renal and parathyroid gland VDR content is an important factor in calcium homeostasis, vitamin D metabolism, and the treatment of secondary hyperparathyroidism and renal osteodystrophy. In these tissues, VDR expression is highly regulated by the calcium and vitamin D status. Although 1,25(OH)2D3 up-regulates VDR expression, hypocalcemia and vitamin D deficiency result in drastically reduced expression of the receptor. The generation of 25-hydroxyvitamin D3-1␣-hydroxylase-null mice, which are incapable of endogenously producing 1,25(OH)2D3, has allowed us to investigate the influence of parathyroid hormone (PTH) on VDR expression independent of PTHmediated increases in 1,25(OH)2D3. Administration of human PTH (1-34) (110 g͞kg per day) for 48 h reduced renal VDR levels from 515 to 435 fmol͞mg protein (15%, P < 0.03) in wild-type mice. In the 25-hydroxyvitamin D3-1␣-hydroxylase-null mice, PTH administration strongly reduced renal VDR levels, from 555 to 394 fmol͞mg protein (29%, P < 0.001). These results demonstrate that PTH is a potent down-regulator of VDR expression in vivo. The biological response to 1,25(OH) 2 D 3 is directly related to the VDR content of target tissues (6, 7). Thus, the regulation of receptor expression is a critical determinant of hormone activity. The VDR has been shown to be developmentally regulated, expressed in a tissue-specific manner, and regulated by a variety of physiological factors and hormones (8). It is well established that 1,25(OH) 2 D 3 can stimulate receptor expression in the kidney and parathyroid gland while having minimal influence on intestinal VDR expression (9-13). Several studies also have noted a positive correlation between calcium and VDR expression. Hypocalcemia induced by dietary calcium restriction dramatically reduces renal VDR levels and prevents 1,25(OH) 2 D 3 from increasing VDR expression (14-16). Reduced dietary calcium also has been associated with diminished VDR mRNA in avian and rat parathyroid gland (11,12). If left untreated, renal failure with subsequent vitamin D deficiency and hypocalcemia will lead to a decrease in parathyroid gland VDR content and the development of vitamin D resistance (17, 18). The molecular trigger responsible for the hypocalcemia-mediated decline in renal and parathyroid gland VDR content is heretofore unknown.PTH expression is inversely related to serum calcium values (19). Because hypocalcemic animals have high circulating levels of PTH and reduced renal and parathyroid gland VDR expression, we hypothesized that PTH may down-regulate VDR expression. Previous investigations into PTH-mediated regulation of VDR expression yielded mixed results. A PTH-mediated increase of VDR and VDR mRNA was reported in osteoblastlike UMR-106 cells (20, 21), whereas a PTH-mediated decrease in VDR and its transcript was reported in ROS 17͞2.8 osteoblast cells (22). In vivo, osmotic PTH adm...

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Parathyroid hormone-induced ornithine decarboxylase activity in fetal rat osteoblasts

Leeuwen

Bos

Herrmann‐Erlee

1989

Journal of Bone and Mineral Research

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Induction of ornithine decarboxylase (ODC, E.C. 4.1.1.17) activity by parathyroid hormone (PTH) in cultured fetal rat osteoblasts was studied. PTH induced ODC activity and stimulated cAMP production in a dose-dependent manner, the ED50 for cAMP being five times as high as that for ODC. Induction of ODC activity by PTH was partly inhibited by actinomycin D and cycloheximide, with 40 and 55% inhibition, respectively. PTH increased the intracellular ionized calcium concentration ([Ca2+]i), which was absent in a Ca2+-free medium. Blocking calcium influx, lowering the extracellular calcium concentration, and adding trifluoperazine inhibited both induction of ODC activity and stimulation of cAMP production by PTH. A23187 (100 nM and 1 microM), combined with a low dose of PTH (4 nM), resulted in a synergistic induction of ODC activity and an inhibition of cAMP production. A23187 inhibited induction of ODC activity as well as stimulation of cAMP production by the dose of PTH (20 nM) maximally effective in inducing ODC activity. Forskolin together with this maximal dose of PTH resulted in an additive effect on ODC activity and a synergistic stimulation of cAMP production. The current results show similarities and differences with respect to results obtained with osteoblasts from other species and osteoblast cell lines. The present data indicate that (1) PTH stimulates ODC activity and this is partly due to new enzyme synthesis; (2) calcium is involved in induction of ODC activity and stimulation of cAMP production by PTH; furthermore, it is suggestive that calmodulin and/or protein kinase C are involved; and (3) stimulation of cAMP production by PTH depends on an optimal intracellular calcium concentration range.

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Heterologous up-regulation of the 1,25-dihydroxyvitamin D3 receptor by parathyroid hormone (PTH) and PTH-like peptide in osteoblast-like cells

Cited by 40 publications

References 11 publications

Modulation by epidermal growth factor of the basal 1,25(OH)2D3 receptor level and the heterologous up-regulation of the 1,25(OH)2D3 receptor in clonal osteoblast-like cells

Modulation by epidermal growth factor of the basal 1,25(OH)2D3 receptor level and the heterologous up-regulation of the 1,25(OH)2D3 receptor in clonal osteoblast-like cells

Parathyroid hormone decreases renal vitamin D receptor expressionin vivo

Parathyroid hormone-induced ornithine decarboxylase activity in fetal rat osteoblasts

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