Mineralocorticoid Hormones Exert Dramatic Effects on Pluripotent Human Stem Cell Progeny

Abstract

The authors studied mineralocorticoid receptor (MCR)-mediated effects of steroids on CD34+ progenitor cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed the presence of m RNA for both the MCR and the alpha subunit of the epithelial sodium channel, a member of the amiloride-sensitive sodium channel (ASSC) superfamily, in human CD41+ megacaryoblastic cells derived from cultured bone marrow CD34+ isolates, as well as in the human erythromegakaryoblastic leukemia (HEL) cell line. Immunofluorescence also revealed the presence of both the MCR and ASSC in circulating CD34+ and medullar CD41+ megacaryoblastic cells, the former as a nucleocy-toplasmic protein and the latter as a membrane-bound protein, as expected from earlier studies using MCR-specific targets. In a selective medium, the formation of erythrocyte burst-forming units, and of the granulocyte-macrophage colony-forming units, by circulating CD34+ cells was influenced by the agonists deoxycorti-costerone and aldosterone, as well as by the antagonists RU 26752 and ZK 91587, targeted for the MCR. The multiplication of the leukemic HEL progeny, derived from CD41+ cells, was similarly altered by these steroids targeted for the MCR. In contrast, in the optimal growth medium, the multiplication, and colony formation by bone marrow CD34+ progenitor cells were not altered by either aldosterone or ZK 91587. These and other studies reveal that the receptor-mediated action of mineralocorticoids may influence the functional maturation of the hematopoietic progenitor lineage, contrary to the classical notion where the mineralotropic effect would be a unique feature of the epithelial cell.