Control of placental protein production by retinoic acid in cultured placental cells.

The synthesis of human chorionic gonadotropin (HCG), the subunit of HCG (HCG alpha), and pregnancy-specific beta 1-glycoprotein (PS beta G) was studied in temperature sensitive (ts), simian virus 40 (SV40) tsA mutant-transformed human first trimester placental (SPA255-26) cells. Retinoic acid increased the production of HCG and PS beta G but inhibited the production of HCG alpha in these cells. Passage of SPA255-26 placental cells in medium containing retinoic acid induced a stable altered phenotype characterized by elevated levels of HCG and PS beta G and a reduced level of HCG alpha. The retinoic acid induced phenotypic changes in these placental cells were reversible; removal of retinoic acid immediately decreased the production of HCG and PS beta G while increasing the production of HCG alpha. The ratio of HCG to HCG alpha in control SPA255-26 cells was approximately 0.1; this ratio increased to 4.8 in cells maintained in medium containing retinoic acid. Similarly, the HCG-to-HCG alpha ratio increased in choriocarcinoma cells maintained in retinoic acid containing medium. Our data suggest that retinoic acid may be needed to maintain a balanced production of HCG, HCG alpha, and PS beta G in placental cells in vitro. Retinoic acid may also play a role in modulating placental protein production during pregnancy.