Erythropoiesis, which is primarily hepatic in the rat during fetal and early neonatal life, shifts almost entirely to the bone marrow in the neonatal-adolescent stage of development. In the adult, extramedullary erythropoiesis has been demonstrated in the liver and spleen under certain pathological conditions when bone marrow red cell production is insufficient. In the present study, erythropoietic foci have been found in young-adult rat liver regenerating 24-72 hr after subtotal hepatectomy. This erythropoiesis is both extravascular and sinusoidal, with some erythroblastic islands noted. The centrolobular hepatic area contains the highest concentration of erythroblasts. Peripheral blood reticulocytosis coincides with the appearance of these cells and this is considered as an indicator of effective erythropoiesis. Liver regenerating after partial hepatectomy produces significant quantities of erythropoietin (Ep) in response to hypoxia. Subtotal hepatectomy may confer upon the adult liver the ability to revert to a fetal-like condition both in its ability to produce Ep and to function as a hematopoietic inductive microenvironment for erythropoiesis.
The E and A series prostaglandins have been reported to stimulate erythropoiesis and renal erythropoietin (Ep) production. In the present study, these prostaglandins also stimulated the elaboration of extrarenal Ep in renoprival animals after hypoxia. This extrarenal response was primarily due to hepatic Ep synthesis; when subtotal hepatectomy (hepx) was followed by nephrectomy, the Ep response to hypoxia was almost completely abolished. The synthetic methylated prostaglandins (16, 16-dimethyl E2 and (15s)-15 methyl E2) exerted the most potent effects on both the hepatic and renal Ep response. It is believed that this is attributable, at least in part, to the greater stability of these compounds in vivo. Rostaglandins do not appear to be capable of substantially elevating Ep production by the regenerating liver. When compared to vehicle-or saline-injected rats, a greater stimulation of hepatic Ep elaboration after prostaglandin treatment was observed in animals with normal livers than in rats with liver regenerating 72 hr after hepx. 23 1 0037-9727l82lO6023 1-06$01 .OO/O
Erythropoietin (Ep) is a glycoprotein hormone that is responsible for mammalian red blood cell production. Adult rat liver regenerating 48-72 h after hepatectomy (hepx) produces elevated levels of Ep in response to hypoxia when compared to sham-operated, anephric hypoxic controls. A factor, termed hepatopoietin (Hp), found in the serum of hepx rats, is capable of stimulating hepatic Ep production when administered to normal rats 18 h prior to hypoxic exposure. Although the hepatic vein is the most potent source of this factor, Hp can also be demonstrated in the systemic arterial circulation. Bilateral nephrectomy (nephrx) of the donor hepx animal 24 h prior to bleeding abolishes this variation, and highest Ep levels are noted when serum from a hepx and nephrx rat is administered to animals immediatley after nephrx and 18 h before hypoxic exposure. Serum derived from hepx male rats displays a greater ability to evoke hepatic Ep production in normal recipients than serum from similarly treated female rats. Regardless of the sex of the hepx donor, Ep elaboration after hypoxia is highest in male recipients. The results indicate that there is a sexual variation in the production of Hp as well as Ep.
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