Polyamine administration reduces ornithine decarboxylase activity without affecting its mRNA content

Abstract

Ornithine decarboxylase, the first enzyme in the polyamine biosynthetic pathway, is induced by androgens in the mouse kidney. Enzyme activity, as well as enzyme protein levels are increased 100–400 fold. Utilizing a specific cDNA probe to ODC, mRNA levels in these cells were found to increase 7–25 fold as measured by densitometric scanning. Treatment of the mice for 5 hours with 2 mmol/kg doses of putrescine or 1,3-diaminopropane after androgen stimulation reduced enzyme activity to control levels, while mRNA levels remained elevated 18–30 fold above control. In a different system, serum starved SV-3T3 cells showed low ODC activity and amounts of ODC mRNA. Serum stimulation increased the 2.2 kilobase mRNA levels 6 fold and enzyme activity 13 fold in a coordinate fashion within 5 hours. While the rise in activity was blocked by the simultaneous addition of serum and 1 mM putrescine, ODC mRNA levels appeared unchanged. The addition of 50 μM spermidine or 100 μM spermine also had no effect on ODC mRNA levels, while at the same time reducing enzyme activity amounts. These results suggest that the mechanism by which polyamines regulate ODC activity in the mouse is primarily translational.