Thyroid Hormone – Metabolism, Transport & Regulation
THYROID HORMONE – METABOLISM, TRANSPORT & REGULATION
- Thyroid gland – Largest endocrine gland.
- Weighing 10-20 gm.
- Two large lobes joined by narrow isthmus wrapped around upper part of trachea.
Microscopical picture:
- Colloid microscopically contains follicles filled with proteinaceous fluid.
- Follicular wall lined by single cellular layer.
- In active gland:
- Single layer of columnar/cuboidal with very little colloid.
Inactive/resting state:
- Squamous with abundant colloid.
- “Parafollicular” cells – Scattered in connective tissue between follicles.
Secretions:
- From thyroid follicular epithelium,
- Tri-iodothyronine (T3) & Tetra-iodothyronine (Thyroxine or T4).
- Both T4 or T3 denotes thyorid hormone.
- Synthesized & stored in thyroid follicles within thyroglobulin molecule.
- T4 & T3 – Iodine derivatives of thyronine.
- Thyronine – Condensation product of 2 amino acid tyrosine molecules.
Chemical structure:
- Thyroxine: 3, 5, 3′, 5′ – tetraiodothyronine
- T3: 3, 5, 3′- triiodothyronine.
Properties:
- Both T4 & T3 have similar physiological actions, yet quantitative differences exist.
- T4 – “Prohormone of T3“.
- T4 is secreted in much larger amounts compared to T3.
- Most T4 is converted to T3 in liver, kidney & pituitary.
- By action of enzyme 5′-deiodinase.
- Hence, T3 -“Principal Thyroid Hormone” finally mediating metabolic effects.
- T4 more stable (more half-life).
- Half-life ofT4 – 6 days.
- Being bound to plasma proteins avidity.
- Hence, T4 – Major circulating hormone.
- Half-life of T3 – 1 day.
- T3 – More avidly bound to nuclear receptor than T4.
- T4 receptor complex is unable to activate/depress gene transcription.
- T3 – More potent & acts faster.
- Hence, T3 – Active hormone.
- T4 – Mainly transport form & functions ” T3 Prohormone”.
- Thyroid gland secretes virtually 100% of circulating T4 & only 20% circulating T3.
- 80% T3 derived from T4.
- By T3 deiodination in peripheral tissues.
TRANSPORT:
- Most circulating form – Protein bound.
- Leaving only 0.02% T4 & about 0.2% T3, unbound or free.
- 3 Hormone binding proteins:
- Thyroxine-binding globulin –
- Major thyroid hormone binding protein.
- Level increase in pregnancy & by drugs estrogens, methadone, heroin, tranquilizers & clofibrate.
- Level decreased by glucocorticoid, androgen, danazol, asparaginase (Cancer chemotherapy) & nephrotic syndrome.
- Thyroxine-binding albumin.
- Thyroxine-binding prealbumin.
METABOLISM:
In target tissue –
- Slowly released from transport proteins pass ing through cell membrane.
- Transport across is affected by number of transport proteins –
- Includes monocarboxylate transporter 8 (MTC 8) & organic anion transporter polypeptide 1C1(OATPIC1) in brain.
- Metabolized in liver,
- By deiodination, deamination & finally conjugation with glucuronic acid.
- Glucuronide conjugate secreted through bile duct into intestine & excreted in feces.
REGULATION:
- TSH controlled – in all steps of thyroid hormone synthesis.
- TSH secretion controlled by hypothalamic hormone TRH.
- Regulateds by “Classical Negative Feedback” mechanism.
- Increased thyroid hormone suppresses TSH & TRH secretion.
- Decreased thyroid hormone stimulates TSH & TRH secretions.
Exam Question
THYROID HORMONE – METABOLISM, TRANSPORT & REGULATION
- T4 & T3 – Iodine derivatives of thyronine.
- Thyronine – Condensation product of two molecules of amino acid tyrosine.
Properties:
- T4 – “Prohormone of T3“.
- Most T4 secreted by thyroid is converted to T3 in liver, kidney & pituitary, by action of enzyme 5′-deiodinase.
- T3 -“Principal Thyroid Hormone”.
- Half-life of T4 – 6 days.
- T4 – Major circulating hormone.
- Half-life of T3 – 1 day.
- T3 – More avidly bound to nuclear receptor than T4.
- T3 – More potent & acts faster.
- Hence, T3 – Active hormone.
- T4 – Mainly a transport form & functions as “Prohormone of T3”.
- Only 20% circulating T3.
TRANSPORT:
Thyroxine-binding globulin-
- Major thyroid hormone binding protein.
- Level increase in pregnancy & by drugs estrogens, methadone, heroin, tranquilizers & clofibrate.
- Level decreased by glucocorticoid, androgen, danazol, asparaginase (Cancer chemotherapy) & nephrotic syndrome.
METABOLISM:
- Transport across target cells affected by number of transport proteins –
- Includes monocarboxylate transporter 8 (MTC 8) & organic anion transporter polypeptide 1C1(OATPIC1) in brain.
- Metabolized in liver
- By deiodination, deamination & finally conjugation with glucuronic acid.
REGULATION:
- Thyroid activity is TSH controlled.
- Thyroid secretion is regulated in “Classical Negative Feedback” mechanism.
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