[A new role for corticosteroid binding globulin (CBG), member of SERPIN superfamily].
Recent advances in molecular endocrinology have shed a new light on the role and mode of action of CBG. It is now not only demonstrated that this plasma glycoprotein, a steroid carrier, can be internalized by glucocorticoid target tissues, but it is also certain that CBG mRNA is synthesized by extra-hepatic tissues. Moreover, some authors have reported a modulation of CBG properties by free fatty acids. The existence of CBG receptors (or high affinity membrane-binding sites), and even a positive effect of CBG on adenylate cyclase activity, have also been reported. To progress in the understanding of these diverse results, one must first integrate them in a general scheme where it is considered that CBG is a member of the SERPIN (SERine Protease INhibitors) superfamily. In the case of CBG, that means a protein which functions as a substrate for elastase at the surface of neutrophils, for instance at sites of inflammation. CBG is specifically cleaved by this protease at a precise site close to its carboxy-terminus. This induces a conformation change and disrupts the binding between glucocorticoids and CBG, and promotes a significant and local release of glucocorticoids (over 90% of them are bound to CBG in human plasma). In this context, CBG directs glucocorticoids to sites of inflammation, and plays in consequence a crucial role in efficient glucocorticoid action in physiology. The elucidation of the CBG sequence, the knowledge of its gene structure, and the discovery of its chromosomal localization near two other SERPIN genes, are three sets of data in concordance to demonstrate that CBG is a SERPIN; and this has allowed the understanding of a new role for CBG, possibly with important consequences in pathology. Moreover, it could be more appropriate to say that CBG is a member of the SERine Protease INhibitors and Substrates superfamily (SERPINS).
Séralini
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GE
URA CNRS 609, Laboratoire de Biochimie, CHU Côte-de-Nacre, Caen, France.
D000818:Animals; D006801:Humans; D014156:Transcortin / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*
D014156:Transcortin
Un rôle nouveau pour la corticosteroid binding globulin (CBG), membre de la superfamille des SERPIN.