Thyroid hormone T3 acting through the thyroid hormone α receptor is necessary for implementation of erythropoiesis in the neonatal spleen environment in the mouse

Abstract

Thyroid hormones (THs) mediate many physiological and developmental functions in vertebrates. All these functions are mediated by binding of the active form of the TH T3 to the specific nuclear receptors TRα and TRβ, which are transcription factors. Using mutant mice lacking TRs or deficient for TH production, we show that T3 influences neonatal erythropoiesis through TRα. The effect of T3 and TRα is restricted to this developmental window and is specific for the spleen but not for other erythropoietic organs. We show that T3 via TRα affects late steps of erythrocytic development, promoting the proliferation of late basophilic erythroblasts. In vitro, this effect is exerted directly on erythrocytic cells. In vivo, the action of T3 is also intrinsic to spleen erythrocytic progenitors, as shown by grafting experiments of splenocytes derived from wildtype and TRα knockout (TRα0/0) mice into wild-type and TRα0/0 irradiated recipients. Our results indicate that defective spleen erythropoiesis in hypothyroid and TRα0/0mice results from impaired recognition of the spleen environment by the mutant erythrocytic progenitors. The data presented support a model in which T3 signaling through TRα is essential for the implementation of the transient spleen erythropoiesis at birth.