Induction of monocytic differentiation of HL-60 cells by 1,25-dihydroxyvitamin D analogs.

摘要: 1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D, induces differentiation HL-60 human promyelocytes into monocyte-like cells in vitro. We assessed relative activity 30 analogs 1,25-dihydroxyvitamin D3 inducing development monocytic markers cells. The three assayed were nonspecific acid esterase activity, nitro blue tetrazolium reducing and phagocytic capacity. Of known metabolites is most active; 50% exhibit mature phenotype following a 4-day treatment with 10(-8) M D3. Removal either C-1 or C-25-hydroxyl group reduces by 2 orders magnitude, while epimerization 1 alpha- to beta-hydroxyl virtually abolishes activity. Elongation steroidal side chain addition one carbon at C-24 C-26 improves potency an order magnitude. Truncation leads 10-fold reduction for each removed. Elimination C-27 methyl groups 100-fold. Analogs short aliphatic chains as alpha-hydroxyhomo- bishomopregnacholecalciferol have surprisingly high being only 20-fold less potent than natural hormone. system parallels their affinities well characterized receptor chick intestine, providing further evidence that this function mediated.