Molecular studies of corticosteroid binding globulin structure, biosynthesis and function.
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.
Hammond
G L
GL
Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.
Smith
C L
CL
Underhill
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D015843:Serpins / Q000502:physiology; D014156:Transcortin / Q000502:physiology* / Q000648:ultrastructure
D015843:Serpins; D014156:Transcortin