Estrone potentiates myeloid cell differentiation: a role for 17 beta-hydroxysteroid dehydrogenase in modulating hemopoiesis
| Autor: | J C, Mountford, C M, Bunce, S V, Hughes, M T, Drayson, D, Webb, G, Brown, M, Hewison |
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| Rok vydání: | 1999 |
| Předmět: |
17-Hydroxysteroid Dehydrogenases
Estradiol Estrone Gene Expression Regulation Leukemic Neutrophils Cell Differentiation HL-60 Cells Tretinoin Fetal Blood Hematopoietic Stem Cells Monocytes Hematopoiesis Neoplasm Proteins Aromatase Gene Expression Regulation Receptors Estrogen Enzyme Induction Humans Protein Isoforms RNA Messenger RNA Neoplasm Cholecalciferol |
| Zdroj: | Experimental hematology. 27(3) |
| ISSN: | 0301-472X |
| Popis: | Hormones such as 1 alpha, 25-dihydroxy vitamin D3 (D3), all-trans retinoic acid, and 9-cis retinoic acid stimulate differentiation of myeloid progenitor cells via their interaction with specific hormone receptors. However, the sensitivity of cells to these agents is not merely governed by the expression of their receptors and the availability of ligand to bind them. Recent studies from our group suggested that the actions of D3 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 myeloid progenitor cells. Quantitative thin-layer chromatography (TLC) analyses showed that HL60 and normal cells are able to generate estrone (E1) from estradiol (E2). Neither cell population generated significant amounts of E2 from E1. Reverse transcriptase polymerase chain reaction and Northern analyses confirmed that normal and leukemic myeloid progenitor cells expressed mRNA for the type I and IV isoforms of 17 beta-hydroxysteroid dehydrogenase. Conversion of E2 to E1 was upregulated within 24 hours when HL60 cells were treated with either all-trans retinoic acid or D3 at doses that induce their differentiation toward neutrophils or monocytes, respectively. Similarly, D3-induced monocyte differentiation of normal myeloid progenitor cells was associated with increased capacity to generate E1 from E2. When HL60 cells or normal myeloid progenitor cells were exposed to exogenous E1 they became more sensitive to the differentiation-inducing effects of D3. Data presented provide further evidence for the local modulation of myelopoiesis by intracrine mechanisms. In particular, our findings suggest that local metabolism of steroids by normal as well as leukemic myeloid cells influences their responsiveness to D3 and retinoids. |
| Databáze: | OpenAIRE |
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