Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan.
Mol Cell Endocrinol. 2013 Jan 30;365(2):153-61. doi: 10.1016/j.mce.2012.10.014. Epub 2012 Nov 2.
Steroid hormones are essential for health in vertebrates. Corticosteroids, for example, have a regulatory role in many physiological functions, such as osmoregulation, respiration, immune responses, stress responses, reproduction, growth, and metabolism. Although extensively studied in mammals and some non-mammalian species, the molecular mechanisms of corticosteroid hormone (glucocorticoids and mineralocorticoids) action are poorly understood in reptiles. Here, we have evaluated hormone receptor-ligand interactions in the American alligator (Alligator mississippiensis), following the isolation of cDNAs encoding a glucocorticoid receptor (GR) and a mineralocorticoid receptor (MR). The full-length alligator GR (aGR) and aMR cDNAs were obtained using 5' and 3' rapid amplification cDNA ends (RACE). The deduced amino acid sequences exhibited high identity to the chicken orthologs (aGR: 83%; aMR: 90%). Using transient transfection assays of mammalian cells, both aGR and aMR proteins displayed corticosteroid-dependent activation of transcription from keto-steroid hormone responsive, murine mammary tumor virus promoters. We further compared the ligand-specifity of human, chicken, Xenopus, and zebrafish GR and MR. We found that the alligator and chicken GR/MR have very similar amino acid sequences, and this translates to very similar ligand specificity. This is the first report of the full-coding regions of a reptilian GR and MR, and the examination of their transactivation by steroid hormones.
甾体激素对脊椎动物的健康至关重要。例如,皮质甾类在许多生理功能中具有调节作用,如渗透调节、呼吸、免疫反应、应激反应、生殖、生长和代谢。尽管在哺乳动物和一些非哺乳动物物种中得到了广泛研究,但在爬行动物中,皮质甾类激素(糖皮质激素和盐皮质激素)作用的分子机制仍知之甚少。在这里,我们评估了美洲鳄(Alligator mississippiensis)中的激素受体-配体相互作用,方法是分离编码糖皮质激素受体(GR)和盐皮质激素受体(MR)的 cDNA。使用 5'和 3'快速扩增 cDNA 末端(RACE)获得全长鳄鱼 GR(aGR)和 aMR cDNA。推导的氨基酸序列与鸡同源物具有高度同一性(aGR:83%;aMR:90%)。使用哺乳动物细胞的瞬时转染测定,aGR 和 aMR 蛋白均显示出对酮甾类激素反应性、鼠乳腺肿瘤病毒启动子的转录的皮质甾依赖性激活。我们进一步比较了人、鸡、非洲爪蟾和斑马鱼 GR 和 MR 的配体特异性。我们发现,鳄鱼和鸡的 GR/MR 具有非常相似的氨基酸序列,这转化为非常相似的配体特异性。这是首次报道了爬行动物 GR 和 MR 的完整编码区,并检查了它们对类固醇激素的反式激活作用。