Effect of androgens on turnover of ornithine decarboxylase in mouse kidney. Studies using labeling of the enzyme by reaction with [14C] alpha-difluoromethylornithine

Abstract

Treatment of male mice with excess androgens increased the activity of renal ornithine decarboxylase 60-fold in the BALB/c strain and 4-fold in the CD-1 strain. Part of the increase in the activity of ornithine decarboxylase was due to a decreased rate of degradation of the enzyme since activity declined more slowly (t1/2 80 min) in androgen-treated BALB/c mice than in controls (t1/2 20 min) when protein synthesis was inhibited by cycloheximide. When ornithine decarboxylase protein was labeled in vivo by injection of [5-14C]difluoromethylornithine, the rate of disappearance of the labeled protein was exactly the same as the rate of loss of ornithine decarboxylase activity when protein synthesis was inhibited by cycloheximide, confirming that ornithine decarboxylase protein does turn over rapidly in vivo. The half-life of another rapidly turning over enzyme important in polyamine metabolism, S-adenosylmethionine decarboxylase, was also increased in the mouse kidney by androgen treatment. These results indicate that steroid hormones can affect the level of certain proteins by changing the rate of degradation and that the labeling of ornithine decarboxylase by reaction with radioactive alpha-difluoromethylornithine in vivo provides a useful method for studying the degradation of this protein.