Potentiation of human erythropoiesis in vitro by thyroid hormone

Abstract

ANAEMIA is a frequent complication of thyroid dysfunction in man, and often remains unexplained, responding only to thyroid hormone replacement therapy^1,2. Thyroid hormone has recently been shown to influence the rate of red blood cell and haemoglobin production^3–7. In addition to stimulating erythropoietin (Ep) production³, thyroid hormone has been reported to act directly on haematopoietic precursors^4,5. The enhancement of murine and canine in vitro erythroid colony growth by thyroid hormone^6,7 suggests that this hormone may have a direct role in the modulation of erythroid proliferation. Studies of murine erythropoiesis support the existence of two distinct, age-structured, Ep responsive populations of committed erythroid precursor cells: the early committed erythroid burst forming unit (BFU-E) and the late committed erythroid colony forming unit (CFU-E)⁸. These populations are distinguished by cell volume, responsiveness to Ep, and proliferative capacity. The BFU-E, a cell which arises from the pluripotent stem cell soon after its commitment to the erythroid line and which has a high Ep-responsive proliferative capacity, seems to be the precursor of the CFU-E, a cell of lower proliferative capacity. Thyroid hormone has been shown to enhance in vitro erythroid colony formation by canine marrow cells, an effect that may be mediated by a receptor with β₂-adrenergic properties⁷. Velocity sedimentation analysis revealed that colony-forming cells stimulated by this hormone sedimented more slowly than colony-forming cells responding to Ep alone⁷. Here, we have extended these studies to human marrow cells and have shown that the ability of thyroid hormone to stimulate the erythroid committed progenitor cell does not seem to be a function of the state of differentiation of this cell. Both CFU-E-derived and BFU-E-derived colony formation were enhanced by the hormone.