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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-10-24
pubmed:abstractText
The effects of epidermal growth factor (EGF) on basal 1,25-dihydroxyvitamin D3 (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)2D3 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)2D3 receptor up-regulation and PTH-stimulated cAMP production, without an effect on the ED50 of the PTH effects. For both PTH responses the IC50 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)2D3 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 up-regulation 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 E2 and forskolin on both 1,25(OH)2D3 binding and cAMP production were inhibited in a similar fashion. On the other hand, dibutyryl cAMP- and 3-isobutyl-1-methylxanthine-stimulated 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)2D3 receptor. The current data suggest that EGF reduces heterologous up-regulation of the 1,25(OH)2D3 receptor independent of as well as dependent on the cAMP messenger system. The EGF effect is nor primarily located at the PTH receptor, at cAMP phosphodiesterase, or at protein kinase A level.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0171-967X
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-42
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
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.
pubmed:affiliation
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article