Spontaneous development of tyrosine aminotransferase activity in fetal liver cultures

Abstract Tyrosine aminotransferase ( l -tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) activity of explants of rat fetal liver cultured in vitro , if cultured after 18 days of gestation, increased very sharply after a short period of time in culture. Increases in activity up to five times the basal values were commonly observed. When liver explants from more immature rat fetuses were cultured, several days in culture were usually required before the increase in tyrosine aminotransferase activity was observed. The spontaneous in vitro induction of tyrosine aminotransferase mimics in many respects the many-fold increase in this enzyme which is observed in vivo in the immediate post-natal period of life. A series of experiments were performed to better understand the factors controlling tyrosine aminotransferase activity during fetal life and to elucidate the mechanisms by which the spontaneous induction occurs in vitro . Serum from fetal or newborn rats did not influence the tyrosine transferase activity of the in vitro cultures. No change in the spontaneous enzyme development was observed when serum from adrenalectomized rats was used instead of horse serum. Hydrocortisone ( 2 × 10 −6 m ) showed an additive effect, whereas glucagon was effective in inducing the enzyme only if added before the spontaneous development had occurred. Actinomycin D partially prevented the spontaneous development of tyrosine aminotransferase. These results are consistent with the hypothesis that synthesis of this enzyme is repressed during gestation. It seems probable that development of tyrosine aminotransferase in vitro occurs by a mechanism similar to that involved in induction by glucagon.