\(\require{AMScd}\) $$\begin{CD} {\downarrow T_{3/4}} @>{stimulates}>> \text{Hypothalamus} @<{stimulates}<< {Cold}\\ @. @V{TRH}V{stimulates}V @.\\ {\uparrow T_{3/4}} @>{inhibits}>> \text{Pituitary} @<{inhibits}<< \substack{\text{Cortisol} \\ \text{dopamine}}\\ @. @V{TSH}V{stimulates}V @.\\ {\text{Iodide}} @>{ion \ trapping}>> \text{Thyroid} @>>> T_4\\ @. @VVV @VVV\\ @. T_3 @<<< \substack{\text{Peripheral} \\ \text{deiodinases}}\\ @. @. @VVV\\ @. @. \substack{rT_3 \\ \text{(inactive)}}\\ \end{CD}$$
Synthesis and release of thyroid hormone
- Iodide taken up into follicular cells of thyroid by secondary active transport with sodium ('iodine trapping")
- Iodide converted to iodine \( 2I^- + 2H_2O_2 +2H^+ \xrightarrow{Thyroid \ peroxidase} I_2 + 2H_2O\)
- Iodine then binds thyroglobilin to produce T3 and T4
- Hormone excreted into follicular colloid
- Colloid uptaken by pinocytosis \(\to\) proteolysis \(\to\) T3 and T4 release basolaterally
- All increased by \(\uparrow TSH \to \ \uparrow cAMP\)
Carriage: Circulates bounds to thyroxine binding globulin, transthyretin, and albumin, >99% protein bound (T4 more than T3).
Metabolism and elimination: Deiodinated in peripheries. T4 half life = 7 days, T3 half life = 7 hours.
Effects of thyroid hormone:
- Bind to thyroid receptors, which are mostly nuclear receptors that modulate gene expression
- Increase BMR by non-specifically increasing cellular enzyme activity
- Decrease efficiency of electron transport chain \(\to\) increased non-activity thermogenesis
- Increased glycolosis and gluconeogenesis
- Increased expression of adrenergic receptors \(\to\ \uparrow\)sensitivity to catecholamines \(\to\) positive inotropy and chronotropy
- Vasodilation
- Increase FFA mobilization from adipose tissue