Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback
Само за регистроване кориснике
2023
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose,
a reaction model for HPT axis with stoichiometric relations between the main reaction species was
postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary
differential equations. This new model has been examined by stoichiometric network analysis (SNA) with the aim
to see if it possesses the ability to reproduce oscillatory ultradian dynamics founded on the internal feedback
mechanism. In particular, a feedback regulation of TSH production based on the interplay between TRH, TSH,
somatostatin and thyroid hormones was proposed. Besides, the ten times larger amount of produced T4 with
respect to T3 in the thyroid gland was successfully simulated. The properties of SNA in combination with
experimental results, were used to determine the unknown parameters (19 rate constants of particular reaction
steps) necessary for n...umerical investigations. The steady-state concentrations of 15 reactive species were tuned
to be consistent with the experimental data. The predictive potential of the proposed model was illustrated on
numerical simulations of somatostatin influence on TSH dynamics investigated experimentally by Weeke et al. in
1975. In addition, all programs for SNA analysis were adapted for this kind of a large model. The procedure of
calculating rate constants from steady-state reaction rates and very limited available experimental data was
developed. For this purpose, a unique numerical method was developed to fine-tune model parameters while
preserving the fixed rate ratios and using the magnitude of the experimentally known oscillation period as the
only target value. The postulated model was numerically validated by perturbation simulations with somatostatin
infusion and the results were compared with experiments available in literature. Finally, as far as we know,
this reaction model with 15 variables is the most dimensional one that have been analysed mathematically to
obtain instability region and oscillatory dynamic states. Among the existing models of thyroid homeostasis this
theory represents a new class that may improve our understanding of basic physiological processes and helps to
develop new therapeutic approaches. Additionally, it may pave the way to improved diagnostic methods for
pituitary and thyroid disorders.
Кључне речи:
Nonlinear dynamics with feedback / Thyroid hormone synthesis / Reaction and mathematical modelling / Hypothalamic-pituitary-thyroid (HPT) axis / Ultradian and circadian rhythmsИзвор:
Computers in Biology and Medicine, 2023, 160, 106980-Издавач:
- Elsevier
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-MESTD-inst-2020-200026)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200146 (Универзитет у Београду, Факултет за физичку хемију) (RS-MESTD-inst-2020-200146)
- Динамика нелинеарних физичкохемијских и биохемијских система са моделирањем и предвиђањем њихових понашања под неравнотежним условима (RS-MESTD-Basic Research (BR or ON)-172015)
- Наноструктурни функционални и композитни материјали у каталитичким и сорпционим процесима (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-45001)
- NES - Physicochemical aspects of rhythmicity in neuroendocrine systems: Dynamic and kinetic investigations of underlying reaction networks and their main compounds (RS-ScienceFundRS-Ideje-7743504)
DOI: 10.1016/j.compbiomed.2023.106980
ISSN: 0010-4825
PubMed: 37141650
Scopus: 2-s2.0-85153888226
Институција/група
IHTMTY - JOUR AU - Kolar-Anić, Ljiljana AU - Čupić, Željko AU - Maćešić, Stevan AU - Ivanović-Šašić, Ana AU - Dietrich, Johannes PY - 2023 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/6416 AB - The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose, a reaction model for HPT axis with stoichiometric relations between the main reaction species was postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary differential equations. This new model has been examined by stoichiometric network analysis (SNA) with the aim to see if it possesses the ability to reproduce oscillatory ultradian dynamics founded on the internal feedback mechanism. In particular, a feedback regulation of TSH production based on the interplay between TRH, TSH, somatostatin and thyroid hormones was proposed. Besides, the ten times larger amount of produced T4 with respect to T3 in the thyroid gland was successfully simulated. The properties of SNA in combination with experimental results, were used to determine the unknown parameters (19 rate constants of particular reaction steps) necessary for numerical investigations. The steady-state concentrations of 15 reactive species were tuned to be consistent with the experimental data. The predictive potential of the proposed model was illustrated on numerical simulations of somatostatin influence on TSH dynamics investigated experimentally by Weeke et al. in 1975. In addition, all programs for SNA analysis were adapted for this kind of a large model. The procedure of calculating rate constants from steady-state reaction rates and very limited available experimental data was developed. For this purpose, a unique numerical method was developed to fine-tune model parameters while preserving the fixed rate ratios and using the magnitude of the experimentally known oscillation period as the only target value. The postulated model was numerically validated by perturbation simulations with somatostatin infusion and the results were compared with experiments available in literature. Finally, as far as we know, this reaction model with 15 variables is the most dimensional one that have been analysed mathematically to obtain instability region and oscillatory dynamic states. Among the existing models of thyroid homeostasis this theory represents a new class that may improve our understanding of basic physiological processes and helps to develop new therapeutic approaches. Additionally, it may pave the way to improved diagnostic methods for pituitary and thyroid disorders. PB - Elsevier T2 - Computers in Biology and Medicine T1 - Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback VL - 160 SP - 106980 DO - 10.1016/j.compbiomed.2023.106980 ER -
@article{ author = "Kolar-Anić, Ljiljana and Čupić, Željko and Maćešić, Stevan and Ivanović-Šašić, Ana and Dietrich, Johannes", year = "2023", abstract = "The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose, a reaction model for HPT axis with stoichiometric relations between the main reaction species was postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary differential equations. This new model has been examined by stoichiometric network analysis (SNA) with the aim to see if it possesses the ability to reproduce oscillatory ultradian dynamics founded on the internal feedback mechanism. In particular, a feedback regulation of TSH production based on the interplay between TRH, TSH, somatostatin and thyroid hormones was proposed. Besides, the ten times larger amount of produced T4 with respect to T3 in the thyroid gland was successfully simulated. The properties of SNA in combination with experimental results, were used to determine the unknown parameters (19 rate constants of particular reaction steps) necessary for numerical investigations. The steady-state concentrations of 15 reactive species were tuned to be consistent with the experimental data. The predictive potential of the proposed model was illustrated on numerical simulations of somatostatin influence on TSH dynamics investigated experimentally by Weeke et al. in 1975. In addition, all programs for SNA analysis were adapted for this kind of a large model. The procedure of calculating rate constants from steady-state reaction rates and very limited available experimental data was developed. For this purpose, a unique numerical method was developed to fine-tune model parameters while preserving the fixed rate ratios and using the magnitude of the experimentally known oscillation period as the only target value. The postulated model was numerically validated by perturbation simulations with somatostatin infusion and the results were compared with experiments available in literature. Finally, as far as we know, this reaction model with 15 variables is the most dimensional one that have been analysed mathematically to obtain instability region and oscillatory dynamic states. Among the existing models of thyroid homeostasis this theory represents a new class that may improve our understanding of basic physiological processes and helps to develop new therapeutic approaches. Additionally, it may pave the way to improved diagnostic methods for pituitary and thyroid disorders.", publisher = "Elsevier", journal = "Computers in Biology and Medicine", title = "Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback", volume = "160", pages = "106980", doi = "10.1016/j.compbiomed.2023.106980" }
Kolar-Anić, L., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A.,& Dietrich, J.. (2023). Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback. in Computers in Biology and Medicine Elsevier., 160, 106980. https://doi.org/10.1016/j.compbiomed.2023.106980
Kolar-Anić L, Čupić Ž, Maćešić S, Ivanović-Šašić A, Dietrich J. Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback. in Computers in Biology and Medicine. 2023;160:106980. doi:10.1016/j.compbiomed.2023.106980 .
Kolar-Anić, Ljiljana, Čupić, Željko, Maćešić, Stevan, Ivanović-Šašić, Ana, Dietrich, Johannes, "Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback" in Computers in Biology and Medicine, 160 (2023):106980, https://doi.org/10.1016/j.compbiomed.2023.106980 . .