Effect of alcohol on the interaction of cortisol with plasma proteins, glucocorticoid receptors and erythrocytes.
Alcohol ingestion stimulates glucocorticoid secretion in animals and normal men. It is generally believed that this effect is mediated through the pituitary-adrenal axis. To investigate its mechanism, we focussed on the effects of ethanol on cortisol binding to plasma proteins and to glucocorticoid receptors, and on cortisol uptake by erythrocytes. Addition of ethanol (up to 800 mg/dl) decreased cortisol binding to albumin and corticosteroid-binding globulin (CBG), causing an increase in the plasma unbound component. Ethanol also decreased cortisol binding to glucocorticoid receptors in normal human peripheral lymphocytes. The uptake of cortisol by erythrocytes was not affected at ethanol concentrations as high as 2000 mg/dl. These results provide new insight to ethanol effects in vivo. The stimulatory effect of ethanol on the pituitary-adrenal axis appears to be attributable in part to a relative ineffectiveness of cortisol in cortisol-responsive cells consequent to ethanol's ability to diminish cortisol binding to glucocorticoid receptors. A compensatory increase in ACTH secretion in response to the relative hypoglucocorticoid state perceived by corticotrophs would result in maintenance of elevated plasma unbound cortisol and cytosol cortisol levels. We conclude that altered interactions of cortisol with its receptors and transport proteins could be pathophysiological components of the changes in adrenocortical function induced by ethanol ingestion.
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
R
R
Hiramatsu
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Nisula
D001798:Blood Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D014156:Transcortin / Q000378:metabolism*
D001798:Blood Proteins; D011965:Receptors, Glucocorticoid; D012709:Serum Albumin; D000431:Ethanol; D014156:Transcortin; D006854:Hydrocortisone