Hormone cascade Hypothalamus Anterior Pituitary Thyroid T3/T4 TRH TSH Increased BMR and protein synthesis
6 Steps of T3/4 Production 1.Thyroglobulin synthesis 2.Uptake and conentration of Iodide (I - ) 3.Oxidation of iodide to iodine (I). By TPO – thyroid peroxidase. 4.Iodination of thyroglobulin. 5.Coupling of 2 iodinated tyrosine molecules to form T3 or T4 6.Secretion
Three forms of thyroid hormones: T4 – Thyroxin. Less active, bound to TBG strongly. T3 – Tri-iodothyronine. More active, less bound but lower levels. rT3 – Reverse T3. Inactived hormone.
T4T3 Total in blood. (nmol/l)1002 Free amount (nmol/l)0.02 (0.02%)0.005 (0.25%) Relative Activity110 Half life7 days1 day Hormones are bound by TBG (Thyroxine Binding Globulin), T4 bound far more strongly. The active hormone is the free hormone. Despite there being less free T3 it is more active than T4 so has more effect. The shortened half life means it will have a temporary effect.
Deiodinases Type I – Extracellular. Converts T4 -> T3. Raise in local T3. Type II – Intracellular. T4 -> T3. Mainly in CNS and pituitary. Type III – Extracellular. T4 -> rT3. CNS and pituitary. May be protective.
Affects Transcription Change in mRNA Altered Protein Synthesis Thyroid Hormone Response
Effects of Thyroid Hormone Metabolism – Affects anabolic and catabolic. Increased BMR Maturation and Differentiation. Neurological Functions – Synapse formation, myelinogenesis, neuronal outgrowth Growth – mainly GH but needs T3/4
Changes in O 2 consumption Resting – around 250ml/min No T3 – around 150ml/min Excess T3 – around 400ml/min Raised O 2 consumption increases ventilation, cardiac output. Use of substrates changes protein/lipid/carbohyrate metabolism. Heat production, weight loss. Lowered muscle mass, increases urea, increases kidney function.