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Molecular studies of corticosteroid binding globulin structure, biosynthesis and function.

G L Hammond1, C L Smith, D A Underhill

  • 1Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.

The Journal of Steroid Biochemistry and Molecular Biology
|January 1, 1991
PubMed
Summary

Corticosteroid binding globulin (CBG) has conserved domains for N-glycosylation and steroid binding. Its liver biosynthesis and gene regulation are key, with potential roles in fetal development and inflammation.

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Area of Science:

  • Biochemistry
  • Genetics
  • Molecular Biology

Background:

  • Corticosteroid binding globulin (CBG) plays a crucial role in transporting steroid hormones.
  • Phylogenetic analysis reveals conserved domains in CBG, including N-glycosylation sites and a steroid-binding region.

Purpose of the Study:

  • To investigate the biosynthesis, gene regulation, and evolutionary relationships of corticosteroid binding globulin (CBG).
  • To explore the functional significance of CBG interactions, particularly in inflammatory responses.

Main Methods:

  • Phylogenetic comparisons of primary protein structure.
  • Analysis of human CBG gene promoter elements and transcription factors.
  • Studies on the ontogeny of CBG biosynthesis in rats.
  • Examination of structural organization and chromosomal location of the human CBG gene.

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Main Results:

  • Conserved domains in CBG identified, including N-glycosylation and steroid-binding regions.
  • Liver identified as the primary site of adult CBG biosynthesis, with liver-specific transcription factor interactions.
  • CBG gene expression detected in other tissues, potentially important for fetal development.
  • Plasma CBG levels may be influenced by clearance rates during pubertal development.
  • Human CBG gene shows close evolutionary relationship to serine proteinase inhibitors, suggesting recent gene duplication.
  • A specific interaction between CBG and elastase on neutrophils may facilitate glucocorticoid delivery to inflammatory sites.

Conclusions:

  • CBG possesses conserved functional domains and is primarily synthesized in the liver.
  • CBG gene expression and regulation are complex, with implications for development and inflammation.
  • Evolutionary analysis suggests CBG arose from gene duplication events.
  • CBG's interaction with neutrophil elastase is a potentially significant mechanism for localized glucocorticoid delivery during inflammation.