B lymphopoiesis is upregulated after orchiectomy and is correlated with estradiol but not testosterone serum levels in aged male rats

Abstract

Previous studies have shown that B lymphopoiesis is augmented after androgen withdrawal in male mice. As an analogy to the skeletal system, some effects of androgens on the proliferation of B cells may be mediated via aromatization into estrogens in vivo. The aim of the present study was to assess the effects of androgen withdrawal on B lymphopoiesis in bone marrow of aged male rats sequentially over a period of 9 months, and to correlate the flow-cytometric findings with changes in systemic levels of sex steroids. We first showed that androgen withdrawal is associated with enhanced B lymphopoiesis in bone marrow of 4-month-old male orchiectomized (ORX) rats, and that the changes in the bone marrow B cell compartment in ORX animals can be reversed by testosterone supplementation. In a subsequent, sequential experiment, we found that orchiectomy induced a sustained rise in Thy 1.1+/CD45R+ bone marrow cells committed for the B cell lineage that lasted for several months in 13-month-old aged rats. In a stepwise model of multiple regression analysis using estradiol, free and total testosterone as independent variables, estradiol was the strongest predictor of the percentage of B precursor cells in bone marrow in aged SHAM and ORX rats. Free and total testosterone did not correlate with B lymphopoiesis in aged SHAM rats. The current experiment has clearly shown that androgen withdrawal upregulates the number of B lineage cells over several months in rat bone marrow. Furthermore, our results provide evidence that estradiol may play an important role as a physiological suppressor of B lymphopoiesis in aged male rats.