Evolution of androgen-regulated ornithine decarboxylase expression in mouse kidney.

The analysis of naturally occurring variations in hormone-regulated gene expression generates insights into the mechanisms governing evolutionary changes in hormone response. In the mouse (genus Mus), kidney ornithine decarboxylase (ODC) expression, which is regulated by androgens, has been modified during evolution. This has resulted in intra- and interspecies variations that have accumulated over a 10-15 million year time period. We have examined ODC expression and its response to androgens in eight Mus species. Induced ODC levels were found to be similar in six of these species. Two species (M. cookii, M. pahari) contain diminished enzyme levels that are the result of different mechanisms. In M. cookii, the low ODC levels reflect reduced ODC mRNA induction in response to hormone. In M. pahari, on the other hand, the low ODC levels are not derived from altered mRNA concentrations, but appear to be due to translational and/or posttranslational effects. Nuclear run-on assays indicate that ODC mRNA induction is associated with increases in rates of ODC gene transcription. The low ODC mRNA level in induced M. cookii reflects a low rate of ODC gene transcription. Thus, both transcriptional and posttranscriptional mechanisms have contributed to modification of the ODC expression phenotype during evolution. The significance of these findings to the evolution of androgen-regulated ODC expression is discussed.