Regulation of cortisol bioavailability--effects on hormone measurement and actionCitation formats

TY - JOUR

T1 - Regulation of cortisol bioavailability--effects on hormone measurement and action

AU - Perogamvros, Ilias

AU - Ray, David W

AU - Trainer, Peter J

PY - 2012/12

Y1 - 2012/12

N2 - Routine assessment of the hypothalamic-pituitary-adrenal axis relies on the measurement of total serum cortisol levels. However, most cortisol in serum is bound to corticosteroid-binding globulin (CBG) and albumin, and changes in the structure or circulating levels of binding proteins markedly affect measured total serum cortisol levels. Furthermore, high-affinity binding to CBG is predicted to affect the availability of cortisol for the glucocorticoid receptor. CBG is a substrate for activated neutrophil elastase, which cleaves the binding protein and results in the release of cortisol at sites of inflammation, enhancing its tissue-specific anti-inflammatory effects. Further tissue-specific modulation of cortisol availability is conferred by corticosteroid 11β-dehydrogenase. Direct assessment of tissue levels of bioavailable cortisol is not clinically practicable and measurement of total serum cortisol levels is of limited value in clinical conditions that alter prereceptor glucocorticoid bioavailability. Bioavailable cortisol can, however, be measured indirectly at systemic, extracellular tissue and cell levels, using novel techniques that have provided new insight into the transport, metabolism and biological action of glucocorticoids. A more physiologically informative approach is, therefore, now possible in the assessment of the hypothalamic-pituitary-adrenal axis, which could prove useful in clinical practice.

AB - Routine assessment of the hypothalamic-pituitary-adrenal axis relies on the measurement of total serum cortisol levels. However, most cortisol in serum is bound to corticosteroid-binding globulin (CBG) and albumin, and changes in the structure or circulating levels of binding proteins markedly affect measured total serum cortisol levels. Furthermore, high-affinity binding to CBG is predicted to affect the availability of cortisol for the glucocorticoid receptor. CBG is a substrate for activated neutrophil elastase, which cleaves the binding protein and results in the release of cortisol at sites of inflammation, enhancing its tissue-specific anti-inflammatory effects. Further tissue-specific modulation of cortisol availability is conferred by corticosteroid 11β-dehydrogenase. Direct assessment of tissue levels of bioavailable cortisol is not clinically practicable and measurement of total serum cortisol levels is of limited value in clinical conditions that alter prereceptor glucocorticoid bioavailability. Bioavailable cortisol can, however, be measured indirectly at systemic, extracellular tissue and cell levels, using novel techniques that have provided new insight into the transport, metabolism and biological action of glucocorticoids. A more physiologically informative approach is, therefore, now possible in the assessment of the hypothalamic-pituitary-adrenal axis, which could prove useful in clinical practice.

KW - Animals

KW - Biological Availability

KW - Humans

KW - Hydrocortisone/blood

KW - Hypothalamo-Hypophyseal System/metabolism

KW - Pituitary-Adrenal System/metabolism

KW - Protein Binding/physiology

KW - Receptors, Glucocorticoid/metabolism

KW - Transcortin/metabolism

U2 - 10.1038/nrendo.2012.134

DO - 10.1038/nrendo.2012.134

M3 - Review article

C2 - 22890008

VL - 8

SP - 717

EP - 727

JO - Nature reviews. Endocrinology

JF - Nature reviews. Endocrinology

SN - 1759-5029

IS - 12

ER -