Hormonal induction of ornithine decarboxylase in rat hepatoma (HTC) cells in culture and its regulation by polyamines

Ornithine decarboxylase (ODC) (EC 4.1.1.17) was induced in log phase HTC cells grown in suspension culture. Induction with dibutyryl cyclic AMP resulted in two fold increase of ODC activity by 3 hours with a return to control levels by 6 hours. Induction with dexamethasone, a synthetic glucocorticoid, showed a slow steady rate of increase, reaching a plateau level of three fold enhancement by about 12 hours; in the continued presence of inducing agent this level was maintained for at least 25 hours. The naturally occurring polyamines spermidine and spermine, at physiological concentrations, abolish cAMP induction whereas they exert no effect on dexamethasone induction. The level of inhibition of the cAMP induction of ODC in HTC cells effected by spermine at 10^-2M is comparable to that seen with ODC isolated from regenerating rat liver. Spermidine, on the other hand, is less effective when used with isolated ODC suggesting that the greater spermidine effect seen when used with whole HTC cells is probably mediated via its transformation to spermine. In all studies, spermine exhibited a greater inhibitory effect than spermine, and the smallest effective inhibitory concentration of spermine was that of 10^-4M with whole HTC cells. It is suggested tht the polyamines inhibit the induction of ODC by interfering with protein synthesis but not mRNA synthesis.