Age-related variations in hepatic regeneration and erythropoietin production in the rat

Erythropoietin (Ep) is produced mainly by the liver and spleen during fetal and neonatal periods and by the kidney during adolescent and adult life. The liver is also an important extrarenal producer of Ep in the hypoxic, anephric adult animal. Subtotal hepatectomy results in a substantial elevation in serum Ep levels at 30-72 hours after hepatectomy in rats subsequently nephrectomized and rendered hypoxic. Ep production is related to the mass of regenerating liver with peak Ep production occurring during times of greatest tissue proliferation. Regenerative and erythropoietic responses to hepatectomy decline with advancing age. Rats undergoing repeated hepatectomies do not recover full liver mass but the initial rate of regeneration increases following each successive hepatectomy. Ep levels decline in anephric hypoxic rats undergoing multiple hepatectomies when compared to sham-operated controls.