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Endocrinology, Vol 133, 2724-2728, Copyright © 1993 by Endocrine Society

ARTICLES

Effects of calcitriol, 22-oxacalcitriol, and calcipotriol on serum calcium and parathyroid hormone gene expression

T Naveh-Many and J Silver
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel.

Calcitriol markedly decreases PTH gene transcription, but because of the concern about hypercalcemia, there is interest in nonhypercalcemic analogs. We have studied the effects of calcitriol, oxacalcitriol, and calcipotriol on serum calcium and PTH mRNA levels in vivo and in vitro. In vivo in rats, calcitriol was the most effective analog in decreasing PTH mRNA levels, with a maximal effect of about 70% at 25-100 pmol after 24 h. Only 100 pmol led to hypercalcemia. Oxacalcitriol led to a maximal decrease in PTH mRNA levels of 44% at 2 and 5 nmol, similar to 1 nmol calcipotriol. Oxacalcitriol at 200 and 500 pmol led to an increase in serum calcium at 3 h, but not at 6 and 24 h, unlike calcitriol (100 pmol) which caused an increase only at 24 h. In vitro, in primary cultures of bovine parathyroid cells, calcitriol and oxacalcitriol both decreased PTH mRNA levels at similar concentrations. Therefore, in vivo calcitriol is the most effective analog studied in decreasing PTH mRNA levels, including a range of doses that does not cause hypercalcemia. Oxacalcalcitriol and calcipotriol are less effective, but have a wider dose range where they do not cause hypercalcemia. The results in vitro confirm that oxacalcitriol and calcitriol both effectively decrease PTH mRNA levels at the same concentration. The marked activity of calcitriol analogs in vitro compared to in vivo probably reflects differences from calcitriol in their pharmacokinetics.


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