Corticosteroid-binding globulin (CBG): spatiotemporal distribution of cortisol in sepsis

Jessica H Lee; Emily J Meyer; Marne A Nenke; Henrik Falhammar; David J Torpy

doi:10.1016/j.tem.2023.01.002

Corticosteroid-binding globulin (CBG): spatiotemporal distribution of cortisol in sepsis

Trends Endocrinol Metab. 2023 Mar;34(3):181-190. doi: 10.1016/j.tem.2023.01.002. Epub 2023 Jan 20.

Authors

Jessica H Lee¹, Emily J Meyer², Marne A Nenke², Henrik Falhammar³, David J Torpy⁴

Affiliations

¹ Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
² Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia; Department of Endocrine and Diabetes, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
³ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: henrik.falhammar@ki.se.
⁴ Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

PMID: 36681594
DOI: 10.1016/j.tem.2023.01.002

Abstract

Corticosteroid-binding globulin (CBG) is a 50-60 kDa circulating glycoprotein with high affinity for cortisol. CBG is adapted for sepsis; its cortisol binding is reduced reversibly by pyrexia and acidaemia, and reduced irreversibly by neutrophil elastase (NE) cleavage, converting high cortisol-binding affinity CBG to a low affinity form. These characteristics allow for the targeted delivery of immunomodulatory cortisol to tissues at the time and body site where cortisol is required in sepsis and septic shock. In addition, high titer inflammatory cytokines in sepsis suppress CBG hepatic synthesis, increasing the serum free cortisol fraction. Recent clinical studies have highlighted the importance of CBG in septic shock, with CBG deficiency independently associated with mortality.

Keywords: CBG; corticosteroid-binding globulin; cortisol; sepsis; transcortin.

Publication types

Review

MeSH terms

Fever
Humans
Hydrocortisone / metabolism
Sepsis*
Shock, Septic* / metabolism
Transcortin / metabolism

Substances

Hydrocortisone
Transcortin