Role of Estrogen Receptor   in Hematopoietic Stem Cell Development and B Lymphocyte Maturation in the Male Mouse

Abstract

Although estrogens and estrogen receptors (ERs) are known to function in the male brain and reproductive tract, few studies have evaluated their involvement in the male hematopoietic and immune systems. This study was undertaken to determine the role of ER alpha in hematopoietic progenitor and B lymphocyte maturation. ERa knockout (ER-/-), wild-type (ER+/+), and radiation chimeric (ER alpha positive Dr negative in either nonhematopoietic or hematopoietic 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 subpopulations. Animals receiving a pharmacological dose (5 mg/kg BW) of 17 beta-estradiol (E-2) with both elements, ER+/+, had decreased early hematopoietic progenitors and a shift toward a mature B cell subpopulation, whereas animals with both elements, ER-/-, showed changes only in early hematopoietic progenitors. Hematopoietic element ER+/+ animals exhibited greater E-2-induced hematopoietic progenitor and B lymphocyte alterations than those having only nonhematopoietic ER alpha. These data indicate that 1) ER alpha is not necessary for regulating male mouse normal hematopoietic progenitor cell proportions, but is involved in B cell regulation; and 2) ER alpha in hematopoietic elements is predominantly responsible for mediating E-2-induced hematopoietic and B cell changes.