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Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change

Endocrine regulation in the hypothalamic-pituitary-thyroid (HPT) axis is orchestrated by physiological circuits which integrate multiple internal and external influences. Essentially, it provides either of the two responses to overt biological challenges: to defend the homeostatic range of a target...

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Autores principales: Hoermann, Rudolf, Pekker, Mark J., Midgley, John E. M., Larisch, Rolf, Dietrich, Johannes W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219553/
https://www.ncbi.nlm.nih.gov/pubmed/35757421
http://dx.doi.org/10.3389/fendo.2022.825107
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author Hoermann, Rudolf
Pekker, Mark J.
Midgley, John E. M.
Larisch, Rolf
Dietrich, Johannes W.
author_facet Hoermann, Rudolf
Pekker, Mark J.
Midgley, John E. M.
Larisch, Rolf
Dietrich, Johannes W.
author_sort Hoermann, Rudolf
collection PubMed
description Endocrine regulation in the hypothalamic-pituitary-thyroid (HPT) axis is orchestrated by physiological circuits which integrate multiple internal and external influences. Essentially, it provides either of the two responses to overt biological challenges: to defend the homeostatic range of a target hormone or adapt it to changing environmental conditions. Under certain conditions, such flexibility may exceed the capability of a simple feedback control loop, rather requiring more intricate networks of communication between the system’s components. A new minimal mathematical model, in the form of a parametrized nonlinear dynamical system, is here formulated as a proof-of-concept to elucidate the principles of the HPT axis regulation. In particular, it allows uncovering mechanisms for the homeostasis of the key biologically active hormone free triiodothyronine (FT3). One mechanism supports the preservation of FT3 homeostasis, whilst the other is responsible for the adaptation of the homeostatic state to a new level. Together these allow optimum resilience in stressful situations. Preservation of FT3 homeostasis, despite changes in FT4 and TSH levels, is found to be an achievable system goal by joining elements of top-down and bottom-up regulation in a cascade of targeted feedforward and feedback loops. Simultaneously, the model accounts for the combination of properties regarded as essential to endocrine regulation, namely sensitivity, the anticipation of an adverse event, robustness, and adaptation. The model therefore offers fundamental theoretical insights into the effective system control of the HPT axis.
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spelling pubmed-92195532022-06-24 Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change Hoermann, Rudolf Pekker, Mark J. Midgley, John E. M. Larisch, Rolf Dietrich, Johannes W. Front Endocrinol (Lausanne) Endocrinology Endocrine regulation in the hypothalamic-pituitary-thyroid (HPT) axis is orchestrated by physiological circuits which integrate multiple internal and external influences. Essentially, it provides either of the two responses to overt biological challenges: to defend the homeostatic range of a target hormone or adapt it to changing environmental conditions. Under certain conditions, such flexibility may exceed the capability of a simple feedback control loop, rather requiring more intricate networks of communication between the system’s components. A new minimal mathematical model, in the form of a parametrized nonlinear dynamical system, is here formulated as a proof-of-concept to elucidate the principles of the HPT axis regulation. In particular, it allows uncovering mechanisms for the homeostasis of the key biologically active hormone free triiodothyronine (FT3). One mechanism supports the preservation of FT3 homeostasis, whilst the other is responsible for the adaptation of the homeostatic state to a new level. Together these allow optimum resilience in stressful situations. Preservation of FT3 homeostasis, despite changes in FT4 and TSH levels, is found to be an achievable system goal by joining elements of top-down and bottom-up regulation in a cascade of targeted feedforward and feedback loops. Simultaneously, the model accounts for the combination of properties regarded as essential to endocrine regulation, namely sensitivity, the anticipation of an adverse event, robustness, and adaptation. The model therefore offers fundamental theoretical insights into the effective system control of the HPT axis. Frontiers Media S.A. 2022-06-09 /pmc/articles/PMC9219553/ /pubmed/35757421 http://dx.doi.org/10.3389/fendo.2022.825107 Text en Copyright © 2022 Hoermann, Pekker, Midgley, Larisch and Dietrich https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Hoermann, Rudolf
Pekker, Mark J.
Midgley, John E. M.
Larisch, Rolf
Dietrich, Johannes W.
Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
title Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
title_full Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
title_fullStr Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
title_full_unstemmed Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
title_short Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
title_sort principles of endocrine regulation: reconciling tensions between robustness in performance and adaptation to change
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219553/
https://www.ncbi.nlm.nih.gov/pubmed/35757421
http://dx.doi.org/10.3389/fendo.2022.825107
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