Corticosteroid-binding globulin: the clinical significance of altered levels and heritable mutations.
Corticosteroid-binding globulin (CBG) is the specific high-affinity plasma transport glycoprotein for cortisol. Stress-induced falls in CBG levels may heighten hypothalamic-pituitary-adrenal axis responses and CBG:tissue interactions may allow targeted cortisol delivery. Three genetic variants of CBG have been identified that reduce cortisol binding affinity and/or CBG levels. These include the Leuven and Lyon mutations which reduce CBG:cortisol binding affinity 3- and 4-fold, respectively, and the null mutation resulting in a 50% (heterozygote) or 100% (homozygote) reduction in CBG levels. The three reported null homozygotes demonstrate that complete CBG deficiency is not lethal, although it may be associated with hypotension and fatigue. The phenotype of a CBG null murine model included fatigue and immune defects. One community-based study revealed that severe CBG mutations are rare in idiopathic fatigue disorders. The mechanisms by which CBG mutations may cause fatigue are unknown. There are preliminary data of altered CBG levels in hypertension and in the metabolic syndrome; however, the nature of these associations is uncertain. Further studies may clarify the functions of CBG, and clinical observations may validate and/or extend the phenotypic features of various CBG mutations.
Gagliardi
Lucia
L
School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
Ho
Jui T
JT
Torpy
David J
DJ
D000818:Animals; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007333:Insulin Resistance / Q000235:genetics; D009154:Mutation; D009765:Obesity / Q000097:blood / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000502:physiology; D011247:Pregnancy / Q000097:blood; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014156:Transcortin / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D014156:Transcortin; D006854:Hydrocortisone