Increased Concentrations of Cyclic GMP in Fetal Liver Cells Stimulated by Erythropoietin

Abstract

Abstract

The hormone erythropoietin stimulates the processes of cellular proliferation and differentiation in erythroid cells. A possible role for cyclic AMP and cyclic GMP in these events was evaluated in cultures of erythroid cells obtained from the livers of 14-day rat feti. A partially purified preparation of erythropoietin (Ep) stimulated ⁵⁹Fe incorporation into heme in a dose- and time-dependent manner, indicating that the fetal liver cells were responsive to this hormone. Ep stimulated an increase in tissue cyclic GMP content in these cultures at 4 to 9 hr of incubation. However, exogenous addition of cyclic GMP to cultures did not affect heme synthesis. In correlation studies in which cyclic GMP levels were determined and thymidine incorporation into DNA was monitored, cyclic GMP did not appear to be related to the Ep-induced stimulation of DNA synthesis. Addition of 8-bromo-cyclic GMP to cultures did not increase DNA synthesis and addition of FUdR to cultures did not alter the Ep-induced increase in cyclic GMP. The elevation in tissue cyclic GMP concentrations produced by this Ep was blocked by an antibody to this hormone. Therefore, it appears that cyclic GMP may be associated with Ep-stimulated events in the proliferating fetal liver cell other than heme synthesis.