Liver to kidney switch of erythropoietin formation

The liver to kidney switch of erythropoietin (Ep) formation was studied in sheep. The switch was initiated in utero during the last third of the gestation period, and was completed by about 40 days after birth. Administration of testosterone or estradiol benzoate to the fetus/newborn resulted in significant changes in the erythropoietic status of the animal, but failed to affect the initiation and/or completion of the switch. In contrast, a significant delay in the start of the switch occurred in thyroidectomized and chronically anemic fetus-newborns. Treatment of the thyroidectomized animals with thyroxin prevented the delay but accelerated the rate at which the switch was completed. These results demonstrate that 1) the transition from the liver to the kidney is initiated in utero by mechanisms which are independent of sex hormonal influences, 2) the acquisition of the Ep-producing capacity by kidneys is accompanied by a gradual decrease in liver Ep formation, and not by a sudden loss of hepatic Ep production, and 3) the onset and/or progression of the liver to kidney switch is profoundly influenced by the functional status of the thyroid gland and by changes in the oxygen supply-demand ratio.