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• W1996804901 abstract "Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3], a vitamin D analog with enhanced efficacy for treatment of osteoporosis, has been found to be less potent than 1,25-dihydroxyvitamin D3 (calcitriol) in suppressing PTH in vivo. To define the mechanism for the latter observation, we compared the effects of eldecalcitol and calcitriol on PTH secretion by bovine parathyroid cells. While the two compounds showed similar potency when the cells were cultured in medium containing 15% newborn calf serum, eldecalcitol was 100 times more potent than calcitriol in the absence of serum. Eldecalcitol has a higher affinity for the serum vitamin D-binding protein (DBP), and therefore binding to DBP, and possibly other serum components, appears to limit the uptake and activity of eldecalcitol in parathyroid cells, providing an explanation for the lower PTH suppressing activity in vivo (100% serum). However, the 100-fold higher activity of eldecalcitol in the absence of serum was unexpected since the VDR affinity for eldecalcitol is eightfold lower than for calcitriol. The enhanced activity was not due to preferential uptake, but to a resistance to metabolism. While 1 nM [3H]calcitriol was completely degraded within 24 h, [3H]eldecalcitol was not metabolized, despite the induction of the vitamin D catabolic enzyme, 24-hydroxylase (CYP24A). The resistance to metabolism is the likely explanation for the higher potency of eldecalcitol in suppressing PTH in cell culture lacking serum. Thus, the unique properties of eldecalcitol in vivo can be attributed, at least in part, to its high-DBP affinity which increases the half-life, but limits the uptake of eldecalcitol, and to its reduced metabolism, which prolongs the activity of this analog in target tissues. J. Cell. Biochem. 112: 1348–1352, 2011. © 2011 Wiley-Liss, Inc." @default.
• W1996804901 created "2016-06-24" @default.
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• W1996804901 date "2011-04-01" @default.
• W1996804901 modified "2023-09-27" @default.
• W1996804901 title "Suppression of PTH by the vitamin D analog eldecalcitol is modulated by its high affinity for the serum vitamin D-binding protein and resistance to metabolism" @default.
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• W1996804901 doi "https://doi.org/10.1002/jcb.23051" @default.
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