Hormonal Regulation of Tyrosine Aminotransferase and Phenylalanine Hydroxylase in Rat Hepatoma Cells Continuously Cultured in a Serum-Free Medium.Effect of Serum, Dexamethasone and Insulin

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Abstract
Rat hepatoma cells (R-Y121B) which can grow under serum-free conditions were used to study the true effect of serum on the induction of the liver-specific enzymes, tyrosine aminotransferase and phenylalanine hydroxylase. R-Y121B was derived from Reuber hepatoma cells (H4-II-E). Serum and dexamethasone similarly induced tyrosine aminotransferase and phenylalanine hydroxylase. Tyrosine aminotransferase activity increased gradually until the 8th h when it reached a plateau. The increase in phenylalanine hydroxylase activity was much slower until the 12th h, then a striking increase in phenylalanine hydroxylase activity occurred up to the 24th h. Insulin also increased tyrosine aminotransferase activity up to the 4th-6th h, then this activity gradually decreased. Insulin did not induce phenylalanine hydroxylase activity. The increase in both enzyme activities due to serum or dexamethasone after 24 h of incubation was partially abolished in the presence of insulin. The degree of the induction of both enzymes by serum differed greatly for the various preparations of sera, but no clear correlation between the preparation of sera and enzyme activities was found. Serum, which contains hormones, including insulin and glucocorticoids, and other unknown factors, evidently plays an important role in the regulation of liver-specific enzyme activities.