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The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.

ABSTRACT: 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 11?-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 extra-adrenal 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 11?-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.

SUBMITTER: Stimson RH

PROVIDER: S-EPMC4392802 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.

Stimson Roland H RH Mohd-Shukri Nor A NA Bolton Jennifer L JL Andrew Ruth R Reynolds Rebecca M RM Walker Brian R BR

The Journal of clinical endocrinology and metabolism 20131220 1

<h4>Context</h4>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.<h4>Objective</h4>We tested the contribution of peri ...[more]

PMID: 24092834

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Project description:The ectopic expression of the glucose-dependent insulinotropic polypeptide receptor (GIPR) in the human adrenal gland causes significant hypercortisolemia after ingestion of each meal and leads to Cushing's syndrome, implying that human GIPR activation is capable of robustly activating adrenal glucocorticoid secretion. In this study, we transiently transfected the human GIPR expression vector into cultured human adrenocortical carcinoma cells (H295R) and treated them with GIP to examine the direct link between GIPR activation and steroidogenesis. Using quantitative RT-PCR assay, we examined gene expression of steroidogenic related proteins, and carried out immunofluorescence analysis to prove that forced GIPR overexpression directly promotes production of steroidogenic enzymes CYP17A1 and CYP21A2 at the single cell level. Immunofluorescence showed that the transfection efficiency of the GIPR gene in H295R cells was approximately 5%, and GIP stimulation enhanced CYP21A2 and CYP17A1 expression in GIPR-introduced H295R cells (H295R-GIPR). Interestingly, these steroidogenic enzymes were also expressed in the GIPR (-) cells adjacent to the GIPR (+) cells. The mRNA levels of a cholesterol transport protein required for all steroidogenesis, StAR, and steroidogenic enzymes, HSD3?2, CYP11A1, CYP21A2, and CYP17A1 increased 1.2-2.1-fold in GIP-stimulated H295R-GIPR cells. These changes were reflected in the culture medium in which 1.5-fold increase in the cortisol concentration was confirmed. Furthermore, the levels of adenocorticotropic hormone (ACTH) receptor and ACTH precursor proopiomelanocortin (POMC) mRNA were upregulated 2- and 1.5-fold, respectively. Immunofluorescence showed that ACTH expression was detected in GIP-stimulated H295R-GIPR cells. An ACTH-receptor antagonist significantly inhibited steroidogenic gene expression and cortisol production. Immunostaining for both CYP17A1 and CYP21A2 was attenuated in cells treated with ACTH receptor antagonists as well as with POMC siRNA. These results demonstrated that GIPR activation promoted production and release of ACTH, and that steroidogenesis is activated by endogenously secreted ACTH following GIP administration, at least in part, in H295R cells.

Dataset Information

The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.

Publications

The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.

Similar Datasets

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