Thyroxine suppresses thrombocytopoiesis and stimulates erythropoiesis in mice.
Thyroxine has been shown in vitro to stimulate erythropoiesis by two mechanisms: a direct, beta 2-adrenergic receptor-mediated stimulation of red cell precursors, and an indirect, erythropoietin-mediated mechanism. Clinical reports have suggested that excess thyroxine also exerts depressive effects on thrombocytopoiesis, but the most sensitive methods of assessing platelet production, i.e., percentage of 35S incorporation into platelets and determination of megakaryocyte size and number, are not appropriate for analysis of platelet production in human patients. The purpose of this study was to use a mouse model to investigate the effects of the hyperthyroid state on erythropoiesis and thrombocytopoiesis, and to assess in vivo the two mechanisms by which thyroxine has been described to stimulate erythropoiesis in vitro. We found that thyroxine administration significantly depressed platelet production and stimulated erythropoiesis in mice. Both the D- and L-isomers of thyroxine in appropriate doses produced this depression of thrombocytopoiesis, and the effect was dose dependent for both isomers. Daily administration of thyroxine:increased blood volume; decreased the peripheral platelet count, total circulating platelet count and mass, percentage of 35S incorporation into platelets, and megakaryocyte number and size; and concurrently increased indices of red cell production (packed cell volume, red blood cell count, total circulating red blood cell count and mass, and reticulocyte count). Additionally, propranolol, a nonspecific beta-blocker, partially reversed the suppression of platelet production by L-thyroxine, lending credence to the assertion that the direct, beta 2-adrenergic receptor-mediated stimulation of the erythroid cell line by thyroxine reported to exist in vitro may also be important in vivo.
Sullivan
P S
PS
Department of Animal Science, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
McDonald
T P
TP
D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D001810:Blood Volume / Q000187:drug effects; D004906:Erythrocyte Count / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D006410:Hematopoiesis / Q000187:drug effects*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D010976:Platelet Count / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology*
D011433:Propranolol; D013974:Thyroxine