Role of cyclic adenosine 3',5'-monophosphate in differentiation of fetal liver cells in vitro.

Regulation of the synthesis of alpha-fetoprotein (AFP), albumin, and transferrin was studied in temperature-sensitive (ts), simian virus 40 (SV40) tsA mutant-transformed rat fetal liver RLA209-15 cells. The intracellular cyclic AMP (cAMP) levels in RLA209-15 cells grown at the nonpermissive temperature (40 degrees C, the temperature at which the cells exhibit the differentiated phenotype) were higher than the levels in these cells grown at the permissive temperature (33 degrees C, the temperature at which these cells exhibit the transformed phenotype). We have shown previously that differentiation of RLA209-15 cells at 40 degrees C was accompanied by increases in AFP, albumin and transferrin. In the present study, we found that 8 bromo-cAMP (8 BrcAMP), cholera toxin and methylisobutylxanthine (MIX), agents that increase intracellular cAMP levels, greatly stimulated the production of AFP, albumin and transferrin. The phosphodiesterase inhibitor MIX was the most effective inducer of AFP and albumin. The kinetics of AFP induction in the presence of 8BrcAMP, cholera toxin and MIX were similar to the kinetics of albumin induction. The positive correlation of cAMP levels and the differentiated state of these cells indicate that cAMP may be one of the factors that maintains differentiation of fetal liver cells in vitro.