Rheaume C, Schonfeld C, Porter C, Berger F G
Department of Biology, University of South Carolina, Columbia 29208.
Mol Endocrinol. 1989 Aug;3(8):1243-51. doi: 10.1210/mend-3-8-1243.
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.
对激素调节基因表达中自然发生的变异进行分析，有助于深入了解激素反应进化变化的调控机制。在小鼠（小家鼠属）中，受雄激素调节的肾脏鸟氨酸脱羧酶（ODC）表达在进化过程中发生了改变。这导致了在1000万至1500万年的时间里积累的种内和种间变异。我们研究了8个小家鼠物种中ODC的表达及其对雄激素的反应。发现其中6个物种中诱导的ODC水平相似。两个物种（库克氏小家鼠、帕哈里小家鼠）的酶水平降低，这是由不同机制导致的。在库克氏小家鼠中，低ODC水平反映了对激素反应时ODC mRNA诱导的减少。另一方面，在帕哈里小家鼠中，低ODC水平并非源于mRNA浓度的改变，而是似乎归因于翻译和/或翻译后效应。细胞核连续转录分析表明，ODC mRNA诱导与ODC基因转录速率的增加有关。诱导的库克氏小家鼠中低ODC mRNA水平反映了ODC基因转录的低速率。因此，转录和转录后机制在进化过程中都对ODC表达表型的改变起到了作用。本文讨论了这些发现对雄激素调节的ODC表达进化的意义。
