ROLE OF CYTOCHROME P450 IN THE CONTROL OF THE PRODUCTION OF ERYTHROPOIETIN

Effects of agents affecting cytochrome P4 5 0 were studied on the production of erythropoietin (Epo) in cultures of the human hepatoma cell line HepG2. Epo was measured by radioimmunoassay of the culture media after 24 H of incubation. The addition of phenobarbital or 3-methylcholanthrene, which induce cytochrome P4 5 0, significantly enhanced the formation of Epo. Likewise, the thyroid hormones T3 and T4 stimulated the rate of the production of Epo. On the other hand, the formation of Epo was lowered following the addition of diethyl-dithiocarbamate or cysteamine chloride, which inhibit cytochrome P4 5 0. These findings support the idea that O2 sensitive hemoproteins of the microsomal mixed-functional oxidases play a role in the control of the synthesis of Epo. © 1990.