Induction of Tyrosine-α-Ketoglutarate Transaminase in Fetal Rat and Fetal Human Liver in Organ Culture

Abstract

Extract: Explants of fetal rat (13 days to term) and fetal human liver (crown to rump length = 9–20 cm) were grown in organ culture. The survival of the explants was examined by histological appearance, mitotic index, and incorporation of precursors of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. Tissues adjusted to the culture system by the 24th hr and remained so throughout the duration of the experiments. A slight increase in tyrosine transaminase activity occurred in control explants during the 3-day period in culture. Eighteen-hour incubation with hydrocortisone (10-6 M), glucagon (5–25 μg/ml), and insulin (0.05–0.5 U/ml) increased tyrosine transaminase levels, 3.1–6.5, 2.5, and 2.3 times the control values, respectively, in 18-day to term fetal rat liver explants. Actinomycin D and cycloheximide completely inhibited the corticosteroid stimulation. Thirteen-day fetal rat liver exhibited no increase in tyrosine transaminase activity after hydrocortisone incubation for 24 hr, whereas glucagon plus dibutyryl cyclic adenosine monophosphate (AMP) did stimulate tyrosine transaminase activity twofold at this developmental stage. No increase in human fetal liver tyrosine transaminase occurred with any of the agents tested.Speculation: These studies support the hypothesis that mammalian liver is incompetent to respond to hormone-induced enzyme synthesis before a certain developmental stage is reached.