Ornithine decarboxylase mRNA in mouse kidney: a low abundancy gene product regulated by androgens with rapid kinetics.

Abstract

We have used ODC gene expression in mouse kidney as the biological marker for studies of early androgen action. Some of the characteristics of this regulation involve its strict androgen specificity, the dependency on functional androgen receptors, the lack of requirement for pituitary hormones, and the ability of physiological androgens to bring about activation of the ODC gene. Some recent findings have revealed an additional intriguing feature in the regulation of ODC gene expression in that androgen sensitivity of ODC stimulation is genetically regulated in the mouse kidney (unpublished observations). One of the mechanisms by which androgens regulate renal ODC synthesis is to increase the concentration of ODC mRNA. Increased accumulation of this mRNA was seen as soon as 6 hr after testosterone administration, and it peaked 24 hr posttreatment. In general, acute changes in immunoreactive ODC concentration and ODC mRNA accumulation had very similar kinetics, suggesting that androgens induced de novo synthesis of ODC by increasing the rate of ODC gene transcription. In addition, there was always a highly significant correlation between the catalytic enzyme activity and immunoreactive enzyme protein concentration indicating that androgens do not specifically regulate the active site of ODC by either activating or inhibiting the enzyme by posttranslational modifications. A typical feature of ODC in virtually all eukaryotic tissues is the extremely rapid turnover rate of the enzyme with a biological half-life of 10-30 min. However, no direct information on the turnover rate of ODC mRNA is currently available, although indirect experiments have assigned a half-life of about seven hours for this mRNA. The availability of cDNA clones for ODC mRNA measurements will now permit us to address this question more directly, and also to investigate a possible role of androgens in the stabilization of ODC mRNA. In this regard it is of interest to note that chronic treatment of mice with pharmacological doses of testosterone prolongs the half-life of ODC protein four- to tenfold.