Tuesday, December 11, 2012

How Thyroid hormone synthesis and secretion are controlled ?


The most important regulator is TSH. This dimeric peptide hormone comprises a specific beta subunit, that bind to receptor and alpha receptor which is common to gonadotrophins; both subunits along with associated carbohydrate moieties are required for bioactivity. TSH secretion has circadian rhythm, plasma concentration being highest between midnight and 4.00h and lowest at midday.  The classic hypothalamo-pituitary-thyroidal axis for regulation of thyroid hormone synthesis is shown below.

Fig. Regulation of Thyroid hormones(Source:Bishop's clinical chemistry) 

TSH itself auto regulates its release from hypothalamus and pituitary. Pituitary have TSH receptors, on binding of TSH its secretion is inhibited. Interaction of TSH receptor antibodies with TSH receptor in pituitary explains why patients with Grave’s disease may continue to have suppressed TSH weeks or months after normal thyroid hormone concentration achieved after therapy.

Other mechanisms like release of cortisol under stress condition, release of cytokines like IL-1, TNF during illness, somatostatin released during malnutrition all these inhibits TSH release. Thus these factors are important during non thyroidal illness (NTI).

TSH acts via cell surface receptor which is coupled to G protein. This receptor has extracellular N-terminal domain for hormone binding, 7 transmembrane domains and short intracellular C-terminal domain involved in activation of G protein modulators of adenylate cyclase-protein kinase A system.  These characteristics are shared with receptors for gonadotropins which has 40% homology in extracellular domain. This may explain the weak thyroid stimulating activity of hCG. Binding of TSH results in activation of AC and accumulation of cAMP. The calcium and phosphoinositol signaling pathways may also be activated by TSH.

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