EFFECTS OF CALCITRIOL, 22-OXACALCITRIOL, AND CALCIPOTRIOL ON SERUM-CALCIUM AND PARATHYROID-HORMONE GENE-EXPRESSION

Calcitriol markedly decreases PTH gene transcription, but because of t he 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 vitr o. In vivo in rats, calcitriol was the most effective analog in decrea sing PTH mRNA levels, with a maximal effect of about 70% at 25-100 pmo l 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 i ncrease in serum calcium at 3 h, but not at 6 and 24 h, unlike calcitr iol (100 pmol) which caused an increase only at 24 h. In vitro, in pri mary cultures of bovine parathyroid cells, calcitriol and oxacalcitrio l 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 hyper calcemia. Oxacalcalcitriol and calcipotriol are less effective, but ha ve a wider dose range where they do not cause hypercalcemia. The resul ts in vitro confirm that oxacalcitriol and calcitriol both effectively decrease PTH mRNA levels at the same concentration. The marked activi ty of calcitriol analogs in vitro compared to in vivo probably reflect s differences from calcitriol in their pharmokinetics.