Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients

Abstract

Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation. In CF, glucocorticoids (GC) are widely used, but their efficacy and benefit/risk ratio are still debated. In plasma, corticosteroid-binding globulin (CBG) binds 90% of GC and delivers them to the inflammatory site. The main goal of this work was to study CBG expression in CF patients in order to determine whether CBG could be used to optimize GC treatment. The expression of CBG was measured in liver samples from CF cirrhotic and non-CF cirrhotic patients by qPCR and Western blot and in lung samples from non-CF and CF patients by qPCR. CBG binding assays with 3H-cortisol and the measurement of the elastase/α1-antitrypsin complex were performed using the plasmas. CBG expression increased in the liver at the transcript and protein level but not in the plasma of CF patients. This is possibly due to an increase of plasmatic elastase. We demonstrated that pulmonary CBG was expressed in the bronchi and bronchioles and its expression decreased in the CF lungs, at both levels studied. Despite the opposite expression of hepatic and pulmonary CBG in CF patients, the concentration of CBG in the plasma was normal. Thus, CBG might be useful to deliver an optimized synthetic GC displaying high affinity for CBG to the main inflammatory site in the context of CF, e.g., the lung.

Corticosteroid-Binding Globulin is expressed in the adrenal gland and its absence impairs corticosterone synthesis and secretion in a sex-dependent manner

“…Here we show for the first time to our knowledge that adrenal glands express CBG, as previously described in other tissues 9,10,16,17,24,25 . Adrenal glands from males and females presented the same amount of CBG when expressed per µg of protein, while the levels were higher in females when expressed per gland, given the larger adrenal gland size in females compared to males.…”

Corticosteroid-binding-globulin (CBG)-deficient mice show high pY216-GSK3β and phosphorylated-Tau levels in the hippocampus

“…We previously described the expression of CBG in the white adipose tissue, lung and adrenal gland [ 28 , 30 , 31 , 33 ]. Lung CBG expression in males is greater than that in females, in contrast to the expression observed in the liver [ 30 , 34 ]. In pro-inflammatory physiological environments, such as diet-induced obesity, CBG expression is increased in white adipose tissue [ 28 ].…”

“…In pro-inflammatory physiological environments, such as diet-induced obesity, CBG expression is increased in white adipose tissue [ 28 ]. CBG expression in the lung is also increased in the cases of acute pancreatitis and cystic fibrosis, which are characterized by serious lung inflammation [ 30 , 34 ]. It has been suggested that circulating CBG may be important in delivering CORT to the brain, where it acts on neurons through fast non-genomic actions to modulate stress-induced behavior, learning, memory retrieval [ 35 ], and consolidation [ 36 ].…”