Effects of glucocorticoids and mineralocorticoids on proliferation and maturation of human peripheral blood stem cells

It has been shown that hematopoietic progenitors can be expanded ex vivo in the presence of various cytokine combinations. Glucocorticoids (GC) are in volved in the self-renewal of erythroid progenitors in chicken. To see whet her cc have a similar effect on hematopoiesis in humans, CD34(+) peripheral blood stem cells were cultured in serum free medium in the presence of a c c, triamcinolone acetonide. However, our results demonstrate an inhibition of both erythroid and granulocyte-macrophage (GM) proliferation and a modif ication of erythroid colony morphology. Furthermore, RU38486 (Mifepristone) , a potent GC antagonist, was unable to reverse the inhibitory effect of tr iamcinolone acetonide. We also identified and characterized another steroid subfamily, the mineralocorticoid (MC) subfamily, in human PB CD34(+) cells . The MC, aldosterone, significantly enhanced GM colony formation and dimin ished the erythroid colony number. Neither of effects were inhibited by ZK9 1587, an antagonist specific to the MC receptor (MCR). In contrast, ZK91537 reversed the stimulatory effect of deoxycorticosterone on GM colony format ion. Cytoplasmic staining for MCR was observed in CD34+ cells incubated wit h a polyclonal antiserum raised against human MCR. To our knowledge, this i s the first demonstration of the presence of MCR in human PB CD34(+) cells. Am. J. Hematol. 62: 65-73, 1999. (C) 1999 Wiley-Liss, Inc.