title: The half-lives of intact and elastase cleaved human corticosteroid-binding globulin (CBG) are identical in the rabbit.
abstract: Corticosteroid-binding globulin (CBG) is a non-inhibitory member of the serpin superfamily of serine protease inhibitors and carries the majority of cortisol in circulation. It can be cleaved by neutrophil elastase at its exposed reactive centre loop which decreases its affinity for cortisol allowing the release of most of the cortisol at sites of inflammation. Intact and elastase cleaved CBG can be distinguished from each other and can coexist in circulation but with unknown half-lives. Here we treated a portion of purified human CBG with elastase, terminated the digestion and then combined this portion with intact human CBG and measured their respective half-lives in rabbits by ELISA. This investigation shows for the first time that the half-lives of intact and elastase cleaved CBG are identical (∼10h). This is an important finding as it implies that in conditions such as sepsis and septic shock where levels of intact CBG are low and the proportion of cleaved CBG is high that this is likely sustained which may affect the CBG mediated targeted delivery of cortisol to sites of inflammation. Furthermore the residual binding of cortisol to cleaved CBG may alter the overall buffering capacity of CBG for cortisol resetting the baseline concentration of free cortisol.
authors: Steroid & Immunobiochemistry Laboratory, Canterbury Health Laboratories, P.O.Box 151, Christchurch 8001, New Zealand. Electronic address: john.lewis@cdhb.health.nz.
authors: John G
authors: JG
authors: Lewis
authors: Christchurch School of Medicine, University of Otago, 2 Riccarton Ave, Christchurch, New Zealand.
authors: Katie
authors: K
authors: Saunders
authors: Christchurch School of Medicine, University of Otago, 2 Riccarton Ave, Christchurch, New Zealand.
authors: Arron
authors: A
authors: Dyer
authors: Steroid & Immunobiochemistry Laboratory, Canterbury Health Laboratories, P.O.Box 151, Christchurch 8001, New Zealand.
authors: Peter A
authors: PA
authors: Elder
mesh_terms: D000818:Animals; D006207:Half-Life; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism*; D011817:Rabbits; D044967:Serum / Q000378:metabolism; D014156:Transcortin / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D014156:Transcortin; D010196:Pancreatic Elastase; D006854:Hydrocortisone
keywords: CBG; Corticosteroid-binding globulin; Cortisol; Elastase; Reactive centre loop; Serpins