Prostaglandin E1 increases in vivo and in vitro calcitriol biosynthesis in rabbits.
Velásquez-Forero F., García P., Triffitt JT., Llach F.
INTRODUCTION: Prostaglandins have an anabolic effect on bone. Possible mediation of this effect is via calcitriol. This study determines in vivo and in vitro effects of PGE(1) on calcitriol synthesis. METHODOLOGY: In vivo: rabbits received intravenous vehicle or prostaglandin E(1) (50 microg/day) for 20 days before measurements of serum total and ionic calcium, magnesium and phosphorus levels, total and bone-specific alkaline phosphatases, 25(OH)D(3), calcitriol, parathyroid hormone and calcitonin. In vitro: rabbit proximal renal tubules were incubated with 25(OH)D(3) (8 microM) together with PGE(1) (2.82 x 10(-6) M) and the prostaglandin receptor inhibitor AH6809 (10(-4) M) in selected samples. After 5 or 30 min incubation, calcitriol production was measured by radioimmunoassay and data analysed statistically. RESULTS: In vivo, in groups receiving PGE(1), levels of total Ca, Mg and calcitriol increased significantly and 25 dihydroxyvitamin D(3), parathyroid hormone and calcitonin remained unchanged. In vitro, PGE(1) increased calcitriol biosynthesis and the prostaglandin inhibitor AH6809 reduced calcitriol levels significantly after prolonged incubation. CONCLUSIONS: In vivo and in vitro results demonstrate that PGE(1) stimulates calcitriol synthesis. This study represent a major advancement in knowledge of bone metabolism.