Up-regulation of steroid sulphatase activity in HL60 promyelocytic cells by retinoids and 1α,25-dihydroxyvitamin D3

Abstract

HL60 promyeloid cells express both classes of oestrogen receptor (ERα and ERβ). 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 17β-oestradiol. Treatment of HL60 cells with retinoids or 1α,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-α 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 1α,25-dihydroxyvitamin D3, there is increased conversion of 17β-oestradiol into oestrone by an oxidative 17β-hydroxysteroid dehydrogenase. Treatment of Caco-2 colon adenocarcinoma cells with all-trans-retinoic acid or 1α,25-dihydroxyvitamin D3 also increases 17β-oestradiol oxidation to oestrone. An increase in local oestrone production therefore occurs in multiple cell types following treatment with retinoids and 1α,25-dihydroxyvitamin D3. The possible involvement of locally produced oestrogenic steroids in regulating the proliferation and differentiation of myeloid cells is discussed.