Department of Psychology, University of British Columbia, Vancouver, BC, Canada.
Brain Behav Immun. 2010 Aug;24(6):908-18. doi: 10.1016/j.bbi.2010.02.008. Epub 2010 Feb 26.
Glucocorticoids (GCs) affect the development of both the immune and nervous systems. To do so, GCs bind to intracellular receptors, mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). In addition, GCs bind to membrane-associated corticosteroid receptors (mCR). Two well-known GCs are corticosterone and cortisol. Whereas corticosterone is the primary GC in zebra finch plasma, cortisol is the primary GC in zebra finch lymphoid organs and is also present in the brain and plasma during development. Here, we characterized binding sites for corticosterone and cortisol in plasma, liver, lymphoid organs, and brain of developing zebra finches. In tissues, we examined both intracellular and membrane-associated binding sites. For intracellular receptors, there were MR-like sites and GR-like sites, which differentially bound corticosterone and cortisol in a tissue-specific manner. For mCR, we found little evidence for membrane-associated receptors in immune organs, but this could be due to the small size of immune organs. Interestingly, cortisol, but not corticosterone, showed a low amount of specific binding to bursa of Fabricius membranes. For neural membranes, corticosterone bound to one site with low affinity but a relatively high B(max), and in contrast, cortisol bound to one site with high affinity but a lower B(max). Our results indicate that intracellular and membrane-associated receptors differentially bind corticosterone and cortisol suggesting that corticosterone and cortisol might have different roles in immune and nervous system development.
糖皮质激素(GCs)影响免疫系统和神经系统的发育。为此,GCs 与细胞内受体、盐皮质激素受体(MR)和糖皮质激素受体(GR)结合。此外,GCs 还与膜相关皮质激素受体(mCR)结合。两种众所周知的 GCs 是皮质酮和皮质醇。虽然皮质酮是斑胸草雀血浆中的主要 GC,但皮质醇是斑胸草雀淋巴器官中的主要 GC,在发育过程中也存在于大脑和血浆中。在这里,我们描述了发育中的斑胸草雀血浆、肝脏、淋巴器官和大脑中皮质酮和皮质醇结合位点的特征。在组织中,我们检查了细胞内和膜相关的结合位点。对于细胞内受体,存在 MR 样位点和 GR 样位点,它们以组织特异性的方式差异结合皮质酮和皮质醇。对于 mCR,我们在免疫器官中几乎没有发现与膜相关受体相关的证据,但这可能是由于免疫器官的体积较小。有趣的是,皮质醇而不是皮质酮,显示出与法氏囊膜的少量特异性结合。对于神经膜,皮质酮与一个低亲和力但相对高 B(max)的位点结合,相比之下,皮质醇与一个高亲和力但低 B(max)的位点结合。我们的研究结果表明,细胞内和膜相关受体对皮质酮和皮质醇的结合具有差异性,这表明皮质酮和皮质醇可能在免疫系统和神经系统发育中发挥不同的作用。