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1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D, induces differentiation of HL-60 human promyelocytes into monocyte-like cells in vitro. We assessed the relative activity of 30 analogs of 1,25-dihydroxyvitamin D3 in inducing development of monocytic markers in HL-60 cells. The three differentiation markers assayed were nonspecific acid esterase activity, nitro blue tetrazolium reducing activity, and phagocytic capacity. Of the known metabolites of vitamin D, 1,25-dihydroxyvitamin D3 is the most active; 50% of the cells exhibit the mature phenotype following a 4-day treatment with 10(-8) M 1,25-dihydroxyvitamin D3. Removal of either the C-1 or C-25-hydroxyl group reduces activity by 2 orders of magnitude, while epimerization of the 1 alpha- to 1 beta-hydroxyl group virtually abolishes activity. Elongation of the steroidal side chain of 1,25-dihydroxyvitamin D3 by addition of one carbon at C-24 or C-26 improves the potency by an order of magnitude. Truncation of the steroidal side chain leads to a 10-fold reduction in activity for each carbon removed. Elimination of the C-26 and C-27 methyl groups reduces activity 100-fold. Analogs with short aliphatic side chains as 1 alpha-hydroxyhomo- and bishomopregnacholecalciferol have surprisingly high activity, being only 20-fold less potent than the natural hormone. The activity of most analogs in the HL-60 system parallels their known relative affinities for the well characterized 1,25-dihydroxyvitamin D3 receptor in chick intestine, providing further evidence that this function of 1,25-dihydroxyvitamin D3 is receptor mediated.
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
October 1996,
Calcified tissue international,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
March 1997,
Leukemia research,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
February 2008,
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
January 1992,
Leukemia research,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
February 1995,
Cancer research,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
November 1995,
Calcified tissue international,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
November 1987,
Biochemical pharmacology,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
October 1983,
Proceedings of the National Academy of Sciences of the United States of America,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
February 1993,
Biochimica et biophysica acta,
V K Ostrem, and
W F Lau, and
S H Lee, and
K Perlman, and
J Prahl, and
H K Schnoes, and
H F DeLuca
December 2007,
Life sciences,
