Sunday, 3 May 2009

How do thyroid hormones work?

The thyroid gland produces two hormones for export: tri-idothyronine (T3, thyroxine) and tetra-iodothyronine (T4).  About 95% of the exported thyroid hormones are in the form of T4, but this situation is complicated by two factors.  Firstly, T3 is 3-4 times as potent as T4, and secondly, the bulk of T3 is formed from T4 by peripheral tissues.  These facts conspire to balance the workload of T3 and T4 somewhat, despite the lopsided nature of their initial secretion.

Like steroid hormones (but unlike most peptide or protein hormones), T3 and T4 must enter the cell to effect any changes.  This they do either by simple diffusion or else by a specific transport mechanism. 

Once inside the cell, they bind to thyroid hormone receptors, of which there are two types (α and β).  The hormone-plus-receptor complex then binds to specific DNA sequences in the promoter area of various genes (these specific regions are sometimes referred to as thyroid response elements).  The effect of this is to either upregulate or downregulate the transcription of these genes, and this is how thyroid hormones create their effects.

Quite a number of genes must be activated (or repressed) for thyroid hormones to have their wide-ranging effects.  Amongst other things, thyroid hormones act on:
  • the heart - increasing the rate and force of contraction
  • the brain - promoting normal brain development and function
  • the bones - promoting normal skeletal growth and development, and accelerating bone turnover
  • the muscles - increasing protein breakdown
  • the gut - increasing carbohydrate absorption
  • the adipose tissue - increasing lipolysis (breakdown of their stored fat)
as well as, generally, increasing the metabolic rate of tissues, thereby increasing oxygen consumption and heat production.

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