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This version published online on June 8, 2006
Endocrinology, doi:10.1210/en.2005-1161
A more recent version of this article appeared on September 1, 2006
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Submitted on September 9, 2005
Accepted on May 30, 2006

The ACTH stimulation test: Contribution of a physiologically-based model developed in horse for its interpretation in different pathophysiological situations encountered in man

ALAIN BOUSQUET-MELOU*, ENRIQUE FORMENTINI, NICOLE PICARD-HAGEN, LAURE DELAGE, VALERIE LAROUTE, and PIERRE-LOUIS TOUTAIN

Unité Mixte de Recherche 181 de Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique et Ecole Nationale Vétérinaire de Toulouse, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, BP87614, 31076 Toulouse cedex 03 France

* To whom correspondence should be addressed. E-mail: a.bousquet-melou{at}envt.fr.

The present study aimed to characterize the adrenal response to ACTH. A model was developed that coupled the non-linear disposition of cortisol with a physiologically-based model for cortisol secretion by the adrenals. It was assumed that the response to ACTH resulted from two mechanisms: a stimulation of the cortisol secretion rate and control of the duration of the secretion. Seven dose levels of ACTH were tested in horses, a species similar to man as regards adrenal function. The main result was that the secretion rate of the adrenal gland can be modelised by a zero-order process that is maximal for a relatively low dose of ACTH (0.1 µg.kg-1). Beyond this dose, the increasing adrenal gland response is only due to the prolongation of the time of its secretion. The consequences of these different features were explored by simulation to reproduce classical pathophysiological situations encountered in man. Our model was able to reproduce and simply explain many adrenal gland responses that are dimmed by the different non-linearities of the system.


Key words: ACTH • cortisol • dose-response • modeling • non-linearity







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