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Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress

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2018
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Authors
Stanojević, A
Marković, V M
Maćešić, Stevan
Kolar-Anić, Ljiljana
Vukojević, V
Article (Published version)
,
The Authors
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Abstract
The sex hormone testosterone (TTS) and the hypothalamic–pituitary–adrenal (HPA) axis mutually control one another’s activity, wherein TTS suppresses corticotrophin releasing hormone (CRH) stimulated HPA axis activity, whereas the activation of HPA axis has an inhibitory effect on TTS secretion. With an intention to explain these phenomena, a network reaction model is developed from the previously postulated stoichiometric models for HPA activity where main dynamic behaviors are controlled by two catalytic steps (one autocatalytic and one autoinhibitory) with respect to cortisol, both found experimentally. The capacity of the model to emulate TTS effects on HPA axis dynamics and its response to acute CRH-induced stress is examined using numerical simulations. Model predictions are compared with empirically obtained results reported in the literature. Thus, the reaction kinetic examinations of nonlinear biochemical transformations that constitute the HPA axis, including the negative feed...back effect of TTS on HPA axis activity, recapitulates the well-established fact that TTS dampens HPA axis basal activity, decreasing both cortisol level and the amplitude of ultradian cortisol oscillations. The model also replicates TTS inhibitory action on the HPA axis response to acute environmental challenges, particularly CRH-induced stress. In addition, kinetic modelling revealed that TTS induced reduction in ultradian cortisol amplitude arises because the system moves towards a supercritical Hopf bifurcation as TTS is being increased. © 2017, The Author(s).

Keywords:
Autoinhibition / Kinetics / Cortisol / Testosterone / Supercritical Hopf bifurcation / Stoichiometric models / Kinetic modelling / Stresses / Reaction kinetics / Mathematical transformations / Kinetic theory
Source:
Reaction Kinetics, Mechanisms and Catalysis, 2018, 123, 1, 17-30
Publisher:
  • Springer Netherlands
Funding / projects:
  • CMST COST Action CM 1304 ‘‘Emergence and Evolution of Complex Chemical Systems’’
  • Dynamics of nonlinear physicochemical and biochemical systems with modeling and predicting of their behavior under nonequilibrium conditions (RS-172015)
  • Nanostructured Functional and Composite Materials in Catalytic and Sorption Processes (RS-45001)

DOI: 10.1007/s11144-017-1315-7

ISSN: 1878-5190

WoS: 000419514200002

Scopus: 2-s2.0-85034231216
[ Google Scholar ]
6
4
URI
https://cer.ihtm.bg.ac.rs/handle/123456789/2920
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
IHTM
TY  - JOUR
AU  - Stanojević, A
AU  - Marković, V M
AU  - Maćešić, Stevan
AU  - Kolar-Anić, Ljiljana
AU  - Vukojević, V
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2920
AB  - The sex hormone testosterone (TTS) and the hypothalamic–pituitary–adrenal (HPA) axis mutually control one another’s activity, wherein TTS suppresses corticotrophin releasing hormone (CRH) stimulated HPA axis activity, whereas the activation of HPA axis has an inhibitory effect on TTS secretion. With an intention to explain these phenomena, a network reaction model is developed from the previously postulated stoichiometric models for HPA activity where main dynamic behaviors are controlled by two catalytic steps (one autocatalytic and one autoinhibitory) with respect to cortisol, both found experimentally. The capacity of the model to emulate TTS effects on HPA axis dynamics and its response to acute CRH-induced stress is examined using numerical simulations. Model predictions are compared with empirically obtained results reported in the literature. Thus, the reaction kinetic examinations of nonlinear biochemical transformations that constitute the HPA axis, including the negative feedback effect of TTS on HPA axis activity, recapitulates the well-established fact that TTS dampens HPA axis basal activity, decreasing both cortisol level and the amplitude of ultradian cortisol oscillations. The model also replicates TTS inhibitory action on the HPA axis response to acute environmental challenges, particularly CRH-induced stress. In addition, kinetic modelling revealed that TTS induced reduction in ultradian cortisol amplitude arises because the system moves towards a supercritical Hopf bifurcation as TTS is being increased. © 2017, The Author(s).
PB  - Springer Netherlands
T2  - Reaction Kinetics, Mechanisms and Catalysis
T1  - Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress
VL  - 123
IS  - 1
SP  - 17
EP  - 30
DO  - 10.1007/s11144-017-1315-7
ER  - 
@article{
author = "Stanojević, A and Marković, V M and Maćešić, Stevan and Kolar-Anić, Ljiljana and Vukojević, V",
year = "2018",
abstract = "The sex hormone testosterone (TTS) and the hypothalamic–pituitary–adrenal (HPA) axis mutually control one another’s activity, wherein TTS suppresses corticotrophin releasing hormone (CRH) stimulated HPA axis activity, whereas the activation of HPA axis has an inhibitory effect on TTS secretion. With an intention to explain these phenomena, a network reaction model is developed from the previously postulated stoichiometric models for HPA activity where main dynamic behaviors are controlled by two catalytic steps (one autocatalytic and one autoinhibitory) with respect to cortisol, both found experimentally. The capacity of the model to emulate TTS effects on HPA axis dynamics and its response to acute CRH-induced stress is examined using numerical simulations. Model predictions are compared with empirically obtained results reported in the literature. Thus, the reaction kinetic examinations of nonlinear biochemical transformations that constitute the HPA axis, including the negative feedback effect of TTS on HPA axis activity, recapitulates the well-established fact that TTS dampens HPA axis basal activity, decreasing both cortisol level and the amplitude of ultradian cortisol oscillations. The model also replicates TTS inhibitory action on the HPA axis response to acute environmental challenges, particularly CRH-induced stress. In addition, kinetic modelling revealed that TTS induced reduction in ultradian cortisol amplitude arises because the system moves towards a supercritical Hopf bifurcation as TTS is being increased. © 2017, The Author(s).",
publisher = "Springer Netherlands",
journal = "Reaction Kinetics, Mechanisms and Catalysis",
title = "Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress",
volume = "123",
number = "1",
pages = "17-30",
doi = "10.1007/s11144-017-1315-7"
}
Stanojević, A., Marković, V. M., Maćešić, S., Kolar-Anić, L.,& Vukojević, V.. (2018). Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress. in Reaction Kinetics, Mechanisms and Catalysis
Springer Netherlands., 123(1), 17-30.
https://doi.org/10.1007/s11144-017-1315-7
Stanojević A, Marković VM, Maćešić S, Kolar-Anić L, Vukojević V. Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress. in Reaction Kinetics, Mechanisms and Catalysis. 2018;123(1):17-30.
doi:10.1007/s11144-017-1315-7 .
Stanojević, A, Marković, V M, Maćešić, Stevan, Kolar-Anić, Ljiljana, Vukojević, V, "Kinetic modelling of testosterone-related differences in the hypothalamic–pituitary–adrenal axis response to stress" in Reaction Kinetics, Mechanisms and Catalysis, 123, no. 1 (2018):17-30,
https://doi.org/10.1007/s11144-017-1315-7 . .

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