Abstract
This paper provides the reader with an overview of our current knowledge of hypothalamic-pituitary-thyroid feedback from a cybernetic standpoint. Over the past decades we have gained a plethora of information from biochemical, clinical, and epidemiological investigation, especially on the role of TSH and other thyrotropic agonists as critical components of this complex relationship. Integrating these data into a systems perspective delivers new insights into static and dynamic behaviour of thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range.
Highlights
As thyroid hormones play a critical role for metabolism, growth, and tissue differentiation, exact and robust regulation of hormone levels is required
Additional mechanisms of homeostasis include autoregulation, where clearance of iodothyronines increases with their plasma levels [64,65,66], increased degradation of TSH in hyperthyroidism [67], possible ultrashort feedback control of TRH secretion, [68] and numerous mechanisms involving control of thyroid hormone transporters and receptor density [15, 17, 69,70,71,72,73]
Using a yeast two-hybrid assay they found the two units to be able to heterodimerize and they confirmed their colocalization in the anterior pituitary and the ability of the resulting heterodimeric protein to bind and activate human TSH receptors, but not LH and FSH receptors [320]. They named the A2/B5 heterodimeric glycoprotein thyrostimulin; other designations are TSH 2 or corticotroph-derived glycoprotein hormone (CGH), as both chains are expressed in corticotrophs of anterior pituitary [337]
Summary
As thyroid hormones play a critical role for metabolism, growth, and tissue differentiation, exact and robust regulation of hormone levels is required. A thyrotropic hormone from anterior pituitary has first been described at the beginning of the 20th century [1, 2], it was not before 1940 that Salter postulated the existence of a control loop linking the pituitary and thyroid gland [3]. Systems theoretic models try to incorporate both data from a molecular level and those from a systemic perspective on the level of the whole organism in an integrative way Depending on their design principles the resulting cybernetic models may facilitate medical decision making and deliver hypotheses that may again serve as a basis for ongoing research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
