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Lookup NU author(s): Professor Brian WalkerORCiD
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Context: Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary- adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue. Objective: We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans. Design: This was a randomized, single-blinded, crossover study. Setting: The study was conducted at a hospital research facility. Participants: Eight normal-weight healthy men participated in the study. Interventions: Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol. Outcome Measures and Results: Plasma cortisol increased similarly after all macronutrient meals (by ∼90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extraadrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11β-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance. Conclusions: Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and glucocorticoids and the contrasting effects of certain diets on postprandial metabolism. (J Clin Endocrinol Metab 99: 160-168, 2014). © Copyright 2014 by The Endocrine Society.
Author(s): Stimson RH, Mohd-Shukri NA, Bolton JL, Andrew R, Reynolds RM, Walker BR
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Endocrinology and Metabolism
Year: 2014
Volume: 99
Issue: 1
Pages: 160-168
Print publication date: 01/01/2014
Online publication date: 03/10/2013
Acceptance date: 16/09/2013
ISSN (print): 0021-972X
ISSN (electronic): 1945-7197
Publisher: Oxford University Press
URL: https://doi.org/10.1210/jc.2013-2307
DOI: 10.1210/jc.2013-2307
PubMed id: 24092834
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