Antagonistic effects of vitamin D and parathyroid hormone on lipoprotein lipase in cultured adipocytes.
The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (calcitriol) and parathyroid hormone (PTH) on synthesis and secretion of lipoprotein lipase (LPL) were studied in 3T3-L1 adipocytes. Expression of the vitamin D receptor was demonstrated by saturation kinetics with radiolabeled calcitriol. Incubation with calcitriol (10(-8) M) for up to 4 d resulted in a time-dependent significant increase in heparin-releasable LPL activity (LPLa) accompanied by a significant increase in LPL mRNA. In contrast, incubation with intact (1-84) PTH (10(-6) to 10(-9) M) produced a time- and dose-dependent significant decrease in LPLa, but no change in LPL mRNA. The effect of PTH (24-h incubation, 10(-8) M) could be prevented by the calcium channel blocker verapamil. Coincubation with both calcitriol and PTH at equimolar concentration (10(-8) M) resulted in an increase in LPLa and LPL mRNA. These data indicate an antagonistic role for calcitriol and PTH in the regulation of LPL, possibly mediated by intracellular calcium, which may contribute to the alterations in lipoprotein metabolism occurring in uremia.
Querfeld
U
U
University Children's Hospital, Cologne, Germany. Uwe.Querfeld@uni-koeln.de
Hoffmann
M M
MM
Klaus
G
G
Eifinger
F
F
Ackerschott
M
M
Michalk
D
D
Kern
P A
PA
D017667:Adipocytes / Q000201:enzymology*; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012680:Sensitivity and Specificity
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D008071:Lipoprotein Lipase; D002117:Calcitriol