Precocious induction of tyrosine aminotransferase mRNA by hydrocortisone in cultured fetal rat hepatocytes at different developmental stages.

Tyrosine-aminotransferase (TAT) is encoded by a liver-specific gene known to be expressed perinatally. Fetal rat hepatocytes (gestation day 19) in primary cultures, in which TAT gene expression is normally undetectable, are induced by hydrocortisone to express TAT-mRNA in a dose-dependent manner (greater than 10(-7) M). In hepatocytes incubated with hydrocortisone, TAT-mRNA levels were marginal after 24 hours, reaching maximal levels at 48 hours. After a pre-incubation of hepatocytes for 24 hours in the absence of hydrocortisone followed by exposure to hydrocortisone (24-48 hours). TAT-mRNA levels were high. Hepatocytes derived from fetuses of gestation days 14 and 17 displayed comparable levels of TAT-mRNA in response to hydrocortisone. These results demonstrate that cultured hepatocytes of gestational stages as early as day 14, which initially do not respond to hydrocortisone by TAT gene induction, undergo a "maturation" process during the initial 24 hours following cultivation, resulting in the acquisition of precocious competence for TAT gene transcription in response to hydrocortisone. This suggests that one or more factor(s), required for hydrocortisone-inducible TAT gene transcription, and not available in fetal liver until birth (Gluecksohn-Waelsch: Cell, 18:225-237, 1979) appear in fetal hepatocytes upon cultivation during this "maturation" period, thus permitting precocious TAT gene expression in vitro.