1-ALPHA,24(S)-DIHYDROXYVITAMIN D-2 - A BIOLOGICALLY-ACTIVE PRODUCT OF1-ALPHA-HYDROXYVITAMIN D-2 MADE IN THE HUMAN HEPATOMA, HEP3B

A major metabolite of the vitamin D analogue 1 alpha-hydroxyvitamin D- 2 in human liver cells in culture has been identified as 1 alpha,24(S) -dihydroxyvitamin D-2 [1 alpha,24(S)-(OH)(2)D-2]. 1 alpha-Hydroxyvitam in D-3 incubated with the same cells gives rise to predominantly 25- a nd 27-hydroxylated products. Our identification of 1 alpha 24(S)-dihyd roxyvitamin D-2 is based on comparisons of the liver cell metabolite;w ith chemically synthesized 1 alpha,24(S)-(OH)(2)D-2 and 1 alpha,24(R)- (OH)(2)D-2 by using HPLC, GC and GC-MS techniques. The stereochemical orientation of the 24-hydroxyl group was inferred after X-ray-crystall ographic analysis of the 24(R)-OH epimer. 1 alpha,24(S)-Dihydroxyvitam in D-2 binds strongly to the vitamin D receptor and is biologically ac tive in growth hormone and chloramphenicol acetyltransferase reporter gene expression systems in vitro, but binds poorly to rat vitamin D-bi nding globulin, DBP. We suggest that this metabolite, 1 alpha,24(S)-(O H)(2)D-2, possesses the spectrum of biological properties to be useful as a drug in the treatment of psoriasis, metabolic bone disease and c ancer.