Rapid Publication Evidence that 1,25-Dihydroxyvitamin D3 Inhibits the Hepatic Production

Abstract. Previous in vitro studies in rachitic rat liver suggested that 1,25-dihydroxyvitamin D in-hibits the hepatic production of 25-hydroxyvitamin D (25-OHD). An investigation therefore was carried out in eight normal subjects to determine whether con-comitant administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 J would alter the response of serum 25-OHD to challenge with vitamin D. In control studies, vitamin D, 100,000 U/d for 4 d, significantly increased mean serum 25-OHD, from 26.3±2.9 to 66.7±12.6 ng/ ml (P < 0.01). In contrast, 1,25(OH)2D3, 2 Ag/d for 4 d, completely prevented an increase in serum 25-OHD in response to the same dose of vitamin D in the same individuals (25.1±2.2 vs. 27.4±5.3 ng/ml, NS). In a post-control study in seven of the normal subjects, vitamin D again significantly increased mean serum 25-OHD, from 18.2±3.1 to 42.8±4.7 ng/ml (P < 0.001). In each of the three studies, mean serum calcium, phosphorus, and creatinine did not change and remained within the normal range. Whereas mean urinary calcium did not change in response to vitamin D alone during the 4 d ofthe two control studies, it increased significantly in the study in which vitamin D and 1,25(OH)2D3 were given together. A dose-response inhibition of the response of serum 25-OHD to vitamin D by 1,25(OH)2D3 was demonstrated in two of the normal subjects. The results provide evidence that 1,25(OH)2D3 inhibits the hepatic synthesis of its precursor 25-OHD in man. Dr. Bell is a Veterans Administration Medical Investigator