Endocrine Abstracts

Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood and is a serine protease inhibitor family member. Plasma CBG has a reactive center loop (RCL) structure that when cleaved by specific proteases, including neutrophil elastase, results in a loss of high affinity steroid-binding activity. Measurements of CBG levels are typically based on functional assays of its steroid-binding capacity or immunoassays, including enzyme-linked immunosorbant assays (ELISAs)...

Adipose exposure to glucocorticoids (GCs) results in visceral adiposity and insulin resistance. Only the unbound, free fraction of GC can diffuse into cells. Corticosteroid binding globulin (CBG) is the major GC carrier, binding 80–85% of circulating GCs with high affinity. Targeted proteolysis of CBG by neutrophil elastase (NE) significantly reduces CBG binding affinity. This suggests that neutrophil-mediated inflammation provides a regulatory mechanism for delivery of G...

Adipose exposure to glucocorticoids (GCs) results in visceral adiposity and insulin resistance. Only the unbound, free fraction of GC can diffuse into cells. Corticosteroid binding globulin (CBG) is the major GC carrier, binding 80–85% of circulating GCs with high affinity. Targeted proteolysis of CBG by neutrophil elastase (NE) significantly reduces CBG binding affinity. This suggests that neutrophil-mediated inflammation provides a regulatory mechanism for delivery of G...

Background: Corticosteroid-binding globulin (CBG) plays a critical role in regulating glucocorticoid bioavailability. During inflammation, plasma CBG behaves as an acute phase “negative” protein due to the down-regulation of hepatic SerpinA6 (Cbg) expression and proteolytic cleavage of CBG. CBG contains a protease-cleavage domain (RCL) that promotes the release of CBG-bound steroids at sites of inflammation. Using an established adjuvant induced art...

Many organs are functionally sexually dimorphic, resulting in profound differences in the activity of several physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The rodent HPA axis matures post-weaning, characterized by parallel increments in adrenal weight, adrenal cortical size and corticosterone secretion. Between postnatal days (PND) 30 to 45, these parameters increase to a greater extent in females compared to males. Over this same interval, h...

Background: Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and controls the circulating free cortisol pool. Proteolytic cleavage by neutrophil elastase is proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. The CORtisol NETwork (CORNET) consortium found that genetic variation at a locus spanning SERPINA1 (encoding alpha-1 antitrypsin, A1AT, the endogenous inhibitor of neutrophil elastase) and SE...

Introduction: Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and modulates free cortisol levels. Observations in vitro show that CBG is cleaved by neutrophil elastase (NE), a mechanism proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. However, detection of cleaved CBG in vivo in human plasma is controversial, and any influence of NE on CBG cleavage has not been tested in vivo...