Positive and Negative cAMP‐Mediated Control of Tyrosine Aminotransferase Synthesis in Reuber H35 Hepatoma Cells

Abstract

Induction of tyrosine aminotransferase (TAT) by N6,O2''-dibutyryl cAMP (Bt2cAMP) in [rat] Reuber H35 hepatoma cells reaches a maximum value between 3-5 h after addition of Bt2cAMP and subsequently decreases in the continuous presence of Bt2cAMP. The kinetics of the increase, i.e. induction, and the decrease, i.e. the repressed state, of the TAT-synthesizing system was investigated under these conditions. The repressed state of the TAT-synthesizing system is not caused by a decrease in the intracellular cAMP concentration. The repressed state is inhibited by actinomycin D (while induction is not inhibited). During the repressed state no effect of dexamethasone on TAT synthesis is found, while during induction Bt2cAMP and dexamethasone act synergistically. Longer starvation of the cells in serum-free medium has no influence on the kinetics of the induction/repressed state curve. The mechanism of the transition to the repressed state of the TAT-synthesizing system is essentially different from the mechanism of deinduction which occurs after removal of the inducer. Moreover, the repressed state of the system is a phenomenon which is induced by Bt2cAMP separately from induction at a different level of protein synthesis.