Hammond G L, Smith C L, Underhill D A
Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.
J Steroid Biochem Mol Biol. 1991;40(4-6):755-62. doi: 10.1016/0960-0760(91)90300-t.
Phylogenetic comparisons of the primary structure of corticosteroid binding globulin (CBG) have revealed several conserved domains that include sites for N-glycosylation and a region which probably represents a portion of the steroid binding site. The major site of CBG biosynthesis in adults is clearly the liver, and the human CBG gene promoter contains sequence elements that interact with liver-specific transcription factors. Low levels of CBG gene expression have been detected in other tissues, and these may be important for fetal development during late gestation when hepatic CBG mRNA levels are low. Studies of the ontogeny of CBG biosynthesis in the rat have also indicated that plasma CBG levels may be influenced by a more rapid clearance of the protein during pubertal development. Analyses of the structural organization and chromosomal location of the human CBG gene have further confirmed its close relationship with the serine proteinase inhibitors, and suggests that CBG, alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin evolved relatively recently by gene duplication. The functional significance of this relationship has been examined and our studies suggest that a specific interaction between CBG and elastase on the surface of neutrophils may represent a physiologically important event that promotes the delivery of glucocorticoids to these cells at sites of inflammation.
皮质类固醇结合球蛋白（CBG）一级结构的系统发育比较揭示了几个保守结构域，其中包括N-糖基化位点以及可能代表类固醇结合位点一部分的区域。成年人中CBG生物合成的主要部位显然是肝脏，人类CBG基因启动子包含与肝脏特异性转录因子相互作用的序列元件。在其他组织中已检测到低水平的CBG基因表达，而在妊娠后期肝脏CBG mRNA水平较低时，这些表达可能对胎儿发育很重要。对大鼠CBG生物合成个体发生的研究还表明，青春期发育期间蛋白质的更快清除可能会影响血浆CBG水平。对人类CBG基因的结构组织和染色体定位的分析进一步证实了它与丝氨酸蛋白酶抑制剂的密切关系，并表明CBG、α1-蛋白酶抑制剂和α1-抗糜蛋白酶是通过基因复制在相对较近的时间进化而来的。已经对这种关系的功能意义进行了研究，我们的研究表明，CBG与中性粒细胞表面的弹性蛋白酶之间的特定相互作用可能代表了一个生理上重要的事件，该事件促进糖皮质激素在炎症部位向这些细胞的传递。
