Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent control of overnight ACTH secretion.

European Journal of Endocrinology
Ali Iranmanesh, Johannes D Veldhuis

Abstract

ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Seven healthy men. An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by >or=77 and 54% respectively (P<0.001). Hypocortisolemia elevated pulsatile ACTH secretion by 8.2- (METY) and 5.3-fold (KTCZ; both P<0.001). Basal ACTH secretion rose by 3.4-fold under METY-induced cortisol depletion (P=0.020). ACTH secretory-burst shape and half-life were stable. ApEn of ACTH release declined overnight (P=0.021) and with the drug (P=0.001), denoting enhanced feedforward coordination. The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism mi...Continue Reading

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Citations

Dec 3, 2015·Current Obesity Reports·Ferdinand RoelfsemaJohannes D Veldhuis
Oct 1, 2013·Metabolism: Clinical and Experimental·Animesh SharmaJohannes D Veldhuis
Aug 27, 2010·Journal of Fish Biology·J F LeatherlandS Barkataki
Apr 30, 2017·The Journal of Clinical Endocrinology and Metabolism·Ferdinand RoelfsemaJohannes D Veldhuis
Feb 27, 2014·American Journal of Physiology. Endocrinology and Metabolism·Eva BoonenGreet Van den Berghe
Nov 5, 2016·The Journal of Clinical Endocrinology and Metabolism·Ferdinand RoelfsemaJohannes D Veldhuis
May 28, 2021·The Journal of Clinical Endocrinology and Metabolism·Peter Y LiuHans P A Van Dongen

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