Estrone potentiates myeloid cell differentiation: A role for 17 beta-hydroxysteroid dehydrogenase in modulating hemopoiesis

Hormones such as 1 alpha,25-dihydroxy vitamin D-3 (D-3), all-trans retinoic acid, and 9-cis retinoic acid stimulate differentiation of myeloid progeni tor cells via their interaction with specific hormone receptors, However, t he sensitivity of cells to these agents is not merely governed by the expre ssion of their receptors and the availability of ligand to bind them. Recen t studies from our group suggested that the actions of D-3 and retinoids on myelopoiesis also are influenced by endogenous mechanisms involving other steroid hormones. In this study we examined the influence of local estrogen metabolism on the differentiation of HL60 cells and normal primitive myelo id progenitor cells, Quantitative thin-layer chromatography (TLC) analyses showed that HL60 and normal cells are able to generate estrone (E-1) from e stradiol (E-2). Neither cell population generated significant amounts of E- 2 from E-1. Reverse transcriptase polymerase chain reaction and Northern an alyses confirmed that normal and leukemic myeloid progenitor cells expresse d mRNA for the type I and IV isoforms of 17 beta-hydroxysteroid dehydrogena se, Conversion of E-2 to E-1 was upregulated within 24 hours when HL60 cell s were treated with either all-trans retinoic acid or D-3 at doses that ind uce their differentiation toward neutrophils or monocytes, respectively. Si milarly, D-3-induced monocyte differentiation of normal myeloid progenitor cells was associated with increased capacity to generate E-1 from E-2. When HL60 cells or normal myeloid progenitor cells were exposed to exogenous E- 1 they became more sensitive to the differentiation-inducing effects of D-3 . Data presented provide further evidence for the local modulation of myelo poiesis by intracrine mechanisms. In particular, our findings suggest that local metabolism of steroids by normal as well as leukemic myeloid cells in fluences their responsiveness to D-3 and retinoids, (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.