1alpha,25-dihydroxyvitamin D3 stimulates steroid sulphatase activity in HL60 and NB4 acute myeloid leukaemia cell lines by different receptor-mediated mechanisms.
Steroid sulphatase is a key enzyme in the biosynthesis of bioactive estrogens and androgens from highly abundant inactive circulating sulphated steroid precursors. Little is known about how the expression/activity of this enzyme is regulated. In this article, we show that of 1alpha,25(OH)2D3 stimulates an increase steroid sulphatase activity in the HL60 myeloid leukaemic cell line that is inhibited by a specific nuclear VDR (VDRnuc) antagonist and unaffected by plasma membrane-associated vitamin D receptor (VDRmem) agonists and antagonists. 1alpha,25(OH)2D3-mediated up-regulation of steroid sulphatase activity in HL60 cells was augmented by RXR agonists, blocked by RXR-specific antagonists, and RAR specific agonists and antagonists had no effect. In contrast, the 1alpha,25(OH)2D3-mediated up-regulation of steroid sulphatase activity in the NB4 myeloid leukaemic cell line was unaffected by the specific VDRnuc and RXR antagonists, but was blocked by a VDRmem-specific antagonist and was increased by VDRmem-specific agonists. The findings reveal that VDRnuc-RXR-heterodimers play a key role in the 1alpha,25(OH)2D3-mediated up-regulation of steroid sulphatase activity in HL60 cells. However, in NB4 cells, VDRnuc-derived signals do not play an obligatory role, and non-genomic VDRmem-derived signals are important.
Hughes
Philip J
PJ
Division of Immunity and Infection, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. P.J.Hughes@bham.ac.uk
Steinmeyer
Andreas
A
Chandraratna
Roshantha A S
RA
Brown
Geoffrey
G
D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000502:physiology*; D043266:Steryl-Sulfatase / Q000378:metabolism*; D015854:Up-Regulation
D008563:Membrane Lipids; D018167:Receptors, Calcitriol; D002784:Cholesterol; D043266:Steryl-Sulfatase; D002117:Calcitriol