Bruder Eric D, Lee Julie J, Widmaier Eric P, Raff Hershel
Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Milwaukee, Wisconsin, USA.
Physiol Genomics. 2007 Apr 24;29(2):193-200. doi: 10.1152/physiolgenomics.00245.2006. Epub 2007 Jan 9.
We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared with pups from normoxic dams fed ad libitum or pair fed to match the decreased maternal food intake that occurs during hypoxia. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results. Hypoxia increased plasma ACTH and corticosterone, while food restriction had no effect. Microarray revealed that many of the genes affected by hypoxia encode proteins that require molecular oxygen (monooxygenases, oxidoreductases, and electron transport), whereas only a few genes known to be involved in adrenal steroidogenesis were affected. Interestingly, the expression of genes involved in mitochondrial function and intermediary metabolism was increased by hypoxia. Real-time PCR detected a small but significant increase in the expression of Cyp21a1 mRNA in the hypoxic adrenal. When decreased maternal food intake was controlled for, the effects of hypoxia were more pronounced, in that real-time PCR detected significant increases in the expression of Star (244%), Cyp21a1 (208%), and Ldlr (233%). The present study revealed that increased plasma corticosterone in rat pups was due to hypoxia per se, and not as a result of decreased food intake by the hypoxic dam. Furthermore, hypoxia induced changes in gene expression that account for more productive and efficient steroidogenesis.
我们假设，出生后暴露于低氧环境的大鼠幼崽中，肾上腺基因表达的变化介导了血浆皮质酮水平的升高和类固醇生成的增加。在本研究中，将大鼠幼崽（及其母鼠）从出生起暴露于低氧环境，并与来自常氧母鼠且自由进食或配对喂食以匹配低氧期间母鼠食物摄入量减少的幼崽进行比较。进行了微阵列分析，随后用实时PCR进行验证。此外，无论微阵列结果如何，通过实时PCR分析参与肾上腺功能的选定基因的表达。低氧增加了血浆促肾上腺皮质激素（ACTH）和皮质酮水平，而食物限制则没有影响。微阵列显示，许多受低氧影响的基因编码需要分子氧的蛋白质（单加氧酶、氧化还原酶和电子传递蛋白），而只有少数已知参与肾上腺类固醇生成的基因受到影响。有趣的是，低氧增加了参与线粒体功能和中间代谢的基因的表达。实时PCR检测到低氧肾上腺中Cyp21a1 mRNA的表达有小幅但显著的增加。当控制母鼠食物摄入量减少时，低氧的影响更为明显，因为实时PCR检测到Star（244%）、Cyp21a1（208%）和Ldlr（233%）的表达显著增加。本研究表明，大鼠幼崽血浆皮质酮水平升高是由于低氧本身，而非低氧母鼠食物摄入量减少的结果。此外，低氧诱导了基因表达的变化，这些变化导致了更高效的类固醇生成。
