Up-regulation of steroid sulphatase activity in HL60 promyelocytic cells by retinoids and 1 alpha,25-dihydroxyvitamin D-3

HL60 promyeloid cells express both classes of oestrogen receptor (ER alpha and ER beta). We show that hydrolysis of oestrone sulphate by steroid sulph atase is a major source of oestrone in HL60 cells, and that most of the rel eased oestrone is not metabolized further to 17 beta -oestradiol. Treatment of HL60 cells with retinoids or 1 alpha ,25-dihydroxyvitamin D-3 increased steroid sulphatase mRNA and activity in parallel with the induction of CD1 1b. an early marker of myeloid differentiation that is expressed before the differentiating cells stop proliferating, Use of agonists and antagonists against retinoid receptor-a and retinoid receptor-X revealed that both clas ses of retinoid receptor can drive steroid sulphatase up-regulation. Steroi d sulphatase activity fluctuates during the cell cycle, being highest aroun d the transition from G1 to S phase. During the differentiation of HL60 cel ls induced by all-trans-retinoic acid or 1 alpha ,25-dihydroxyvitamin D-3, there is increased conversion of 17 beta -oestradiol into oestrone by an ox idative 17 beta -hydroxysteroid dehydrogenase. Treatment of Caco-2 colon ad enocarcinoma cells with all-trans-retinoic acid or 1 alpha ,25-dihydroxyvit amin D-3 also increases 17 beta -oestradiol oxidation to oestrone, An incre ase in local oestrone production therefore occurs in multiple cell types fo llowing treatment with retinoids and 1 alpha ,25-dihydroxyvitamin D-3, The possible involvement of locally produced oestrogenic steroids in regulating the proliferation and differentiation of myeloid cells is discussed.