The action of erythropoietin is mediated by lipoxygenase metabolites in murine fetal liver cells.

Erythroid progenitor cells synthesize 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) when stimulated by erythropoietin (Ep). Maximal stimulation of 12-HETE production occurred at one hour, whereas 15-HETE activity remained constant in response to Ep for 24 hours. Lipoxygenase-selective inhibitors of arachidonic acid metabolism blocked HETE production and Ep-stimulated growth and differentiation of erythroid progenitor cell-derived colonies (CFU-E). On the other hand, specific inhibitors of cyclooxygenase (aspirin and meclofenamate) did not significantly inhibit Ep-induced erythroid colony formation. It is hypothesized that the stimulation of HETE production from arachidonic acid (AA) is an essential step in the mechanism of action of Ep.