The role of thyroglobulin in thyroid hormonogenesis

Triiodothyronine secretion in early thyroid failure: The adaptive response of central feedforward control

“…31,32 Central regulation involving TRH and tanycytes is also incompletely understood and could only be partly implemented. 14 In hypothyroid patients, functional and symptomatic responses to LT4 vary considerably, displaying a high degree of individuality. 34 While our approach integrates central and local control, thereby denying an autonomy exclusively assigned to local control elements, it does not diminish the importance of their modulatory role in various tissues.…”

“…TSH dependency of T3 production has been supported by in vitro and in vivo studies but was only recently incorporated into a model of hypothalamic-pituitary-thyroid regulation. 7,[11][12][13][14]28 Importantly, unlike phenomenological models, our model is based on physiologically rooted parameters and Michaelis-Menten-Hill kinetics. Mathematically connecting chains of physiological events may generate unforeseen hypotheses, which then can be clinically assessed.…”

“…37 The biochemical mechanisms involve TSH-stimulated iodination of the thyroglobulin molecule, thereby favouring T3 production over T4. 14 In hypothyroid patients, functional and symptomatic responses to LT4 vary considerably, displaying a high degree of individuality. 38 Homeostatic modelling can deliver a personalised equilibrium solution using a set of intrinsic characteristics or structural parameters and various systemic processes uniquely responding to external perturbations and challenges.…”

“…6 TSH feedforward control has only recently been formally introduced to thyroid modelling. 5,[11][12][13][14] The present extension included additional terms at the hypothalamic level, representing specific elements of the hypothalamic regulation of TRH by tanycytes ( Figure S1). 10 Here, we used five nonlinear ODEs of first order to model the feedback regulation of pituitary TSH and hypothalamic TRH by thyroid hormones together with the feedforward control of intra-thyroidal T3 production by the pituitary hormone.…”

“…Within the thyroid, T3 generation originates from two distinct pathways, either de novo synthesis from proteolysis of thyroglobulin or conversion from T4 via monodeiodination with two enzymes, deiodinase 1 and deiodinase 2, both of which are activated by TSH. 5,[11][12][13][14] The present extension included additional terms at the hypothalamic level, representing specific elements of the hypothalamic regulation of TRH by tanycytes ( Figure S1). A detailed description of the underlying equations and physiological parameters is given in the Appendix S1.…”