Role of estrogen receptor alpha in hematopoietic stem cell development andB lymphocyte maturation in the male mouse

Although estrogens and estrogen receptors (ERs) are known to function in th e male brain and reproductive tract, few studies have evaluated their invol vement in the male hematopoietic and immune systems. This study was underta ken to determine the role of ER alpha in hematopoietic progenitor and B lym phocyte maturation. ERa knockout (ER-/-), wild-type (ER+/+), and radiation chimeric (ER alpha positive Dr negative in either nonhematopoietic or hemat opoietic elements, or both) male mice were used to determine target tissues . ER-/- and ER+/+ animals showed similar hematopoietic progenitor profiles, but the ER-/- animals had fewer cells in all bone marrow B lymphocyte subp opulations. Animals receiving a pharmacological dose (5 mg/kg BW) of 17 bet a-estradiol (E-2) with both elements, ER+/+, had decreased early hematopoie tic progenitors and a shift toward a mature B cell subpopulation, whereas a nimals with both elements, ER-/-, showed changes only in early hematopoieti c progenitors. Hematopoietic element ER+/+ animals exhibited greater E-2-in duced hematopoietic progenitor and B lymphocyte alterations than those havi ng only nonhematopoietic ER alpha. These data indicate that 1) ER alpha is not necessary for regulating male mouse normal hematopoietic progenitor cel l proportions, but is involved in B cell regulation; and 2) ER alpha in hem atopoietic elements is predominantly responsible for mediating E-2-induced hematopoietic and B cell changes.