The effects of short-term, high-dose treatment with prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in monocytes from normal human subjects.
Animal and cell culture studies indicate glucocorticoid regulation of 1,25-dihydroxyvitamin D3 receptors and interference with cellular effects of vitamin D. These investigations prompted us to examine the effects of prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in freshly isolated human monocytes. Eighteen normal subjects were studied in a randomized, double-blind, placebo-controlled study. Analysis of receptor kinetics revealed that the maximal nuclear uptake (Bmax) of (3H)-1,25-dihydroxyvitamin D3 in monocytes decreased 40% (P less than .001) after prednisone treatment. In the group treated with prednisone (40 mg/d for 5 days) s-1,25-dihydroxyvitamin D increased 46% (P less than .01). S-25-Hydroxyvitamin D, S-phosphat, S-calcium, and S-iPTH remained unchanged. Osteoblastic production of the matrix protein, bone gla protein (BGP) is stimulated by 1,25-dihydroxyvitamin D3. However, despite increased serum levels of 1,25-dihydroxyvitamin D3, the prednisone-treated group revealed a 75% reduction in s-BGP. The present data indicate that corticosteroids decrease the nuclear uptake of 1,25-dihydroxyvitamin D3 in human monocytes. Further investigations are necessary, however, to elucidate the biologic mechanism for this observation and whether the mechanism is operative in other human tissues including bone.
Nielsen
H K
HK
Department of Medical Endocrinology, Arhus Amtssygehus, Denmark.
Eriksen
E F
EF
Storm
T
T
Mosekilde
L
L
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin; D011241:Prednisone / Q000494:pharmacology*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects* / Q000378:metabolism
D002135:Calcium-Binding Proteins; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002118:Calcium; D011241:Prednisone