Summary 1,25-dihydroxyvitamin D
3 (1,25(OH)
2D
3) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that
25-hydroxyvitamin D
3 (25(OH)D
3) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the
latter activity is due to conversion of 25OHD
3 to 1,25(OH)
2D
3 by HL-60, we exposed HL-60 cells to 25OHD
3 and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane),
a new peak appears which migrates with authentic 1,25(OH)
2D
3. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD
3 (19-Nor-25OHD
3). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have
undergone differentiation. We next determined if authentic 19-Nor-25OHD
3 also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and
macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60
with a potency of approximately 1/200 that of 1,25(OH)
2D
3 and similar to that of 25OHD
3. In agreement with the effect upon cell maturation, 19-Nor-25OHD
3 displaces
3H-1,25(OH)
2D
3 from its HL-60 receptor with an efficiency comparable to 25OHD
3. Hence, HL-60 cells convert 25OHD
3 to 19-Nor-25OHD
3, and 19-Nor-25OHD
3 induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD
3.
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