Levillain Olivier, Greco Anna, Diaz Jean-Jacques, Augier Roger, Didier Anne, Kindbeiter Karine, Catez Frédéric, Cayre Myriam
Laboratoire de Physiopathologie Métabolique et Rénale, Faculté de Médecine Lyon RTH Laënnec, Institut National de la Santé et de la Recherche Médicale, Unite 499, Lyon, France.
Am J Physiol Renal Physiol. 2003 Sep;285(3):F498-506. doi: 10.1152/ajprenal.00407.2002. Epub 2003 Apr 22.
Polyamines are involved in the control of the cell cycle and cell growth. In murine kidney, testosterone enhances gene expression of ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis. In this study, we document the time course effect of testosterone on 1) gene expression of ODC, antizyme 1 (AZ1), and spermidine/spermine-N1-acetyltransferase (N1-SSAT); 2) ODC activity in proximal convoluted tubules (PCT) and cortical proximal straight tubules (CPST); and 3) renal polyamine levels. Female mice were treated with testosterone for a period of 1, 2, 3, and 5 consecutive days. ODC gene expression was extremely low in kidneys of untreated female mice compared with that of males. Consequently, the renal putrescine level was sevenfold lower in females than in males, whereas spermidine and spermine levels did not differ between sexes. In female kidneys, testosterone treatment sharply increased ODC mRNA and protein levels as well as ODC activity. Testosterone increased the expression of ODC in PCT and CPST over different time courses, which suggests that ODC activity is differentially regulated in distinct tubules. The expression of AZ1 and N1-SSAT mRNA was similar in male and female mouse kidneys. Testosterone treatment enhanced AZ1 and N1-SSAT mRNA levels in a time-dependent manner by unknown molecular mechanisms. Putrescine and spermidine levels increased after testosterone treatment in female kidneys. Surprisingly, although ODC protein and activity were undetectable in female kidneys, the levels of AZ1 mRNA and protein were similar to those in males. Therefore, one may propose that ODC protein could be continuously degraded by AZ1 in female kidneys.
多胺参与细胞周期和细胞生长的调控。在小鼠肾脏中，睾酮可增强鸟氨酸脱羧酶（ODC）的基因表达，ODC是多胺生物合成的首个酶。在本研究中，我们记录了睾酮对以下方面的时间进程效应：1）ODC、抗酶1（AZ1）和亚精胺/精胺-N1-乙酰转移酶（N1-SSAT）的基因表达；2）近端曲管（PCT）和皮质近端直小管（CPST）中的ODC活性；3）肾脏多胺水平。对雌性小鼠连续1、2、3和5天给予睾酮治疗。与雄性小鼠相比，未治疗的雌性小鼠肾脏中ODC基因表达极低。因此，雌性小鼠肾脏中的腐胺水平比雄性低7倍，而亚精胺和精胺水平在两性之间没有差异。在雌性小鼠肾脏中，睾酮治疗显著增加了ODC mRNA和蛋白质水平以及ODC活性。睾酮在不同时间进程中增加了PCT和CPST中ODC的表达，这表明ODC活性在不同的肾小管中受到差异调节。雄性和雌性小鼠肾脏中AZ1和N1-SSAT mRNA的表达相似。睾酮治疗通过未知的分子机制以时间依赖性方式提高了AZ1和N1-SSAT mRNA水平。雌性小鼠肾脏经睾酮治疗后腐胺和亚精胺水平升高。令人惊讶的是，尽管在雌性小鼠肾脏中未检测到ODC蛋白和活性，但AZ1 mRNA和蛋白质水平与雄性相似。因此，有人可能提出，在雌性小鼠肾脏中，ODC蛋白可能会被AZ1持续降解。
