Modeling the hypothalamus-pituitary-adrenal axis: A review and extension.
Multiple models of the hypothalamus-pituitary-adrenal (HPA) axis have been developed to characterize the oscillations seen in the hormone concentrations and to examine HPA axis dysfunction. We reviewed the existing models, then replicated and compared five of them by finding their correspondence to a dataset consisting of ACTH and cortisol concentrations of 17 healthy individuals. We found that existing models use different feedback mechanisms, vary in the level of details and complexities, and offer inconsistent conclusions. None of the models fit the validation dataset well. Therefore, we re-calibrated the best performing model using partial calibration and extended the model by adding individual fixed effects and an exogenous circadian function. Our estimated parameters reduced the mean absolute percent error significantly and offer a validated reference model that can be used in diverse applications. Our analysis suggests that the circadian and ultradian cycles are not created endogenously by the HPA axis feedbacks, which is consistent with the recent literature on the circadian clock and HPA axis.
Department of Industrial and Systems Engineering, Virginia Tech, 544 Whittemore Hall, Blacksburg, VA 24061, USA . Electronic address: hniyou4@vt.edu.
Niyousha
N
Hosseinichimeh
MIT Sloan School of Management, E62-462, 100 Main St., Cambridge, MA 02142, USA . Electronic address: hazhir@mit.edu.
Hazhir
H
Rahmandad
Department of Human Development and Family Studies, Michigan State University, 552 W Circle Drive, East Lansing, MI 48824, USA . Electronic address: andreaw@msu.edu.
Andrea K
AK
Wittenborn
D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D008954:Models, Biological; D010913:Pituitary-Adrenal System
Circadian cycle; Dynamics; HPA axis; Mathematical modeling; Partial calibration; Ultradian cycle