title: Up-regulation of steroid sulphatase activity in HL60 promyelocytic cells by retinoids and 1alpha,25-dihydroxyvitamin D3.
abstract: HL60 promyeloid cells express both classes of oestrogen receptor (ERalpha and ERbeta). We show that hydrolysis of oestrone sulphate by steroid sulphatase is a major source of oestrone in HL60 cells, and that most of the released oestrone is not metabolized further to 17beta-oestradiol. Treatment of HL60 cells with retinoids or 1alpha,25-dihydroxyvitamin D3 increased steroid sulphatase mRNA and activity in parallel with the induction of CD11b, an early marker of myeloid differentiation that is expressed before the differentiating cells stop proliferating. Use of agonists and antagonists against retinoid receptor-alpha and retinoid receptor-X revealed that both classes of retinoid receptor can drive steroid sulphatase up-regulation. Steroid sulphatase activity fluctuates during the cell cycle, being highest around the transition from G1 to S phase. During the differentiation of HL60 cells induced by all-trans-retinoic acid or 1alpha,25-dihydroxyvitamin D3, there is increased conversion of 17beta-oestradiol into oestrone by an oxidative 17beta-hydroxysteroid dehydrogenase. Treatment of Caco-2 colon adenocarcinoma cells with all-trans-retinoic acid or 1alpha,25-dihydroxyvitamin D3 also increases 17beta-oestradiol oxidation to oestrone. An increase in local oestrone production therefore occurs in multiple cell types following treatment with retinoids and 1alpha,25-dihydroxyvitamin D3. The possible involvement of locally produced oestrogenic steroids in regulating the proliferation and differentiation of myeloid cells is discussed.
authors: LRF Differentiation Programme, Division of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. p.j.hughes@bham.ac.uk
authors: P J
authors: PJ
authors: Hughes
authors: L E
authors: LE
authors: Twist
authors: J
authors: J
authors: Durham
authors: M A
authors: MA
authors: Choudhry
authors: M
authors: M
authors: Drayson
authors: R
authors: R
authors: Chandraratna
authors: R H
authors: RH
authors: Michell
authors: C J
authors: CJ
authors: Kirk
authors: G
authors: G
authors: Brown
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D001192:Arylsulfatases / Q000096:biosynthesis / Q000378:metabolism*; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers; D004790:Enzyme Induction; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043266:Steryl-Sulfatase; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004970:Estrone; D014212:Tretinoin; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; D002117:Calcitriol; C017296:estrone sulfate