Expression of Corticosteroid-Binding Globulin CBG in the Human Heart

Abstract

• ▶ human myocardium • ▶ adrenal steroids • ▶ mineralocorticoid receptor • ▶ stress hormones • ▶ corticosteroid binding globulin Expression of Corticosteroid-Binding Globulin CBG in the Human Heart nently elevated plasma cortisol levels are associated with higher morbidity and mortality and increased cardiovascular risk [ 7 ]. In an experimental setting with adrenal ectomized rats, administration of cortisol and dexamethasone increased infarct size [ 8 ]. In this light it remains unclear how systemic adrenal steroids aff ect the heart: The benefi cial eff ects of MR inhibitors may relate to a blockade of mineralocorticoids [ 9 ] ; however, the actions of glucocorticoids need to be reinvestigated in this context. Cardiac remodeling has been shown to occur even in MR-deficient mice [ 10 ]. So some of the GC eff ects on cardiomyocytes may involve mechanisms independent from nuclear MR. While a huge body of clinical and physiological literature exists in this fi eld, there are only few morphological studies in humans so far. Corticosteroid-binding globulin (CBG) is a heterodimeric glycoprotein [ 11 ] with high affi nities to GC mineralocorticoids (MC). CBG is primarily expressed in liver [ 12 ] , capable of binding more

Corticosteroid-Binding Globulin: A Review of Basic and Clinical Advances

“…Hence CBG may be important extracellularly in the provision of free cortisol to the GR through the actions of local (as yet unidentified) proteases, from an increase in temperature or intracellularly in transporting cortisol to the nucleus of target cells following CBG receptor-cortisol complex internalisation or local production [69,73]. CBG has also been found in abundance in the cytoplasm and on cell membranes of human cardiomyocytes, co-localised with mineralocorticoid receptors, along with evidence of local CBG production [26,69]. Elastase has also been demonstrated in the cytoplasm and cell membranes of cardiomyocytes [69].…”

“…Elastase has also been demonstrated in the cytoplasm and cell membranes of cardiomyocytes [69]. Thus CBG may participate actively in glucocorticoid signalling in the heart [26,74]. Whether this involves extracellular or intracellular CBG, and whether the effects are genomic or non-genomic remains uncertain.…”

“…CBG is predominantly synthesised by hepatocytes, with its promoter region responding to liver-specific transcription factors [22,23]. CBG mRNA has been identified in other human tissues [4,[24][25][26][27][28] implying localised synthesis. Cortisol-bound CBG binds to cell membranes and activates secondary messenger systems suggesting intrinsic biological activity [29][30][31]; however, the CBG receptor has not been characterised or cloned in humans, with only indirect in vitro evidence of its existence, but has been partially characterised in rats [32] ( • ▶ Fig.…”

Asn347 Glycosylation of Corticosteroid-binding Globulin Fine-tunes the Host Immune Response by Modulating Proteolysis by Pseudomonas aeruginosa and Neutrophil Elastase

“…for Asn 9 , Asn 154 , Asn 238 , and Asn 308 , all BS2; for Asn 74 , TeS4; and for Asn 347 , TS3, based on our previous report (36) using Glycam-web). An asialo version of the fully glycosylated CBG was also generated.…”

“…CBG regulates the bioavailability of this anti-inflammatory steroid hormone by binding up to 90% of the entire cortisol pool with high affinity and specificity in a single binding pocket in a temperature-sensitive manner (1,2). Although produced primarily by hepatocytes (3,4), human CBG mRNA and protein have been found in smaller amounts in other tissues, including lungs, kidneys, testes, placenta, endometrium, fallopian tube, heart, and some regions of the brain (5)(6)(7)(8)(9)(10)(11)(12). The varying circulatory levels of CBG in childhood, puberty, and adulthood and in different physiological states like pregnancy have been documented; for example, the CBG concentration in the blood of healthy individuals was measured to be ϳ40 mg/l (13).…”