Effects of adenosine cyclic nucleotides on the synthesis of human chorionic gonadotropin in transformed human placental cells

Abstract

The synthesis of human chorionic gonadotropin (HCG) and its subunits was studied in simian virus 40 (SV40) tsA mutant-transformed human first-trimester and term placental cells at 33 degrees (the temperature at which the cells have the transformed phenotype) and at 40 degrees (the temperature at which the tsA transformants regain their nontransformed phenotype). 8-Bromo cyclic adenosine 3':5'-monophosphate (8BrcAMP) and dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) greatly induced the synthesis of human chorionic gonadotropin alpha (HCG alpha) with little or no stimulation of the synthesis of HCG in transformed placental cells grown at 33 degrees or 40 degrees. The ratio of HCG alpha to HCG in these cells, therefore, increased in the presence of either nucleotide. 8BrcAMP and Bt2cAMP also greatly induced the synthesis of HCG alpha in nontransformed secondary placental cells (at 6th to 20th passage), although the synthesis of HCG was not detectable in these cells under the experimental conditions used. The synthesis of HCG as well as HCG alpha was stimulated in choriocarcinoma cells by 8BrcAMP and Bt2cAMP. The ratio of HCG alpha to HCG in uninduced choriocarcinoma cells increased during growth in culture. 8BrcAMP stimulated the synthesis of HCG preferentially in these cells, thus decreasing the ratio of HCG alpha to HCG. Our data indicate that adenosine cyclic nucleotides have different effects on the production of HCG but not on HCG alpha in SV40 tsA-transformed placental cells and choriocarcinoma cells.