The Effect of Parathyroid Hormone on Erythropoiesis in Serum-Free Cultures of Fetal Mouse Liver Cells

Abstract

The effects of parathyroid hormone (PTH) on erythropoiesis in serum-free cultures of fetal mouse liver cells were investigated to determine if PTH might, at least partially, be responsible for the anemias of uremia, hyperparathyroidism, and spaceflight. Both crude and pure preparations of PTH were employed with similar effects. PTH at concentrations 10-100 times “normal” produced a dose-dependent stimulation of erythropoiesis which was only observed in the complete absence of exogenous erythropoietin (Ep). Although the responses to both PTH and Ep were calcium-dependent pharmacological analysis of the PTH log-dose/log-response relationship showed the PTH effect to be markedly different from that of Ep. At concentrations approximately 240 times normal PTH inhibited both endogenous and Ep-mediated heme synthesis. These concentrations are considerably greater than those reported in uremia, hyperparathyroidism, or during spaceflight casting doubt on the hypothesis that PTH is directly responsible for the anemia seen in these disorders. Unit gravity cell separation experiments showed that PTH both stimulated and inhibited the Ep-responsive cells as a function of its concentration.