Antogonistic effects of retinoic acid and triiodothyronine in the expression of corticoid-binding globulin (CBG) by cultured fetal hepatocytes

Cultures of rat fetal hepatocytes were used to investigate the effects and interplay of triiodothyronine (T₃) and retinoic acid (RA) in the regulation of gene expression of CBG, compared to that of -fetoprotein (AFP). The cultured cells showed cytological features typical to hepatocytes and actually synthesized CBG and AFP, as evidenced from in situ hybridization with specific radioactive and cell mRNA levels disappeared with a half-life of about 2 days, thereby reflecting the decrease previously seen in hepatic CBG mRNA contents during embryonic life. The K_d values for CBG binding were unchanged under these conditions. Culturing of hepatocytes in the presence of T₃ resulted in dose-dependent stimulations of both medium CBG and cell mRNA levels, with an EC₅₀ concentration of about 10^?9 M. In sharp contrast, RA caused a reduction in CBG biosynthesis (IC₅₀ = 1.7 × 10^?7 M) and, in addition, antagonized the stimulatory influence of T₃. Under the same experimental conditions, AFP synthesis failed to be affected in a similar fashion. We conclude that thyroid hormones and RA directly act on hepatocytes to specifically regulate the expression of CBG in an antagonistic way.