Thyroid gland of Endocrine System

Butterfly-shaped gland in anterior neck on the trachea, just inferior to larynx, that consists of:

• Isthmus: median mass connecting two lateral lobes

• Follicles: hollow sphere of epithelial follicular cells that produce glycoprotein thyroglobulin

• Colloid: fluid of follicle lumen containing thyroglobulin plus iodine and is precursor to thyroid hormone

• Parafollicular cells: produce hormone calcitonin

Thyroid hormone is

Body’s major metabolic hormone

Thyroid hormone found in two forms

• T₄ (thyroxine): major form that consists of two tyrosine molecules with four bound iodine atoms

• T₃ (triiodothyronine): form that has two tyrosines with three bound iodine atoms

  • Must be converted to T₄ at tissue level

• Both are iodine-containing amine hormones

Throid hormone

Enters target cell and binds to intracellular receptors within nucleus

• Triggers transcription of various metabolic genes

Thyorid hormone effects-

• Increases basal metabolic rate and heat production

  • Referred to as calorigenic effect

  • Regulates tissue growth and development

    • Critical for normal skeletal and nervous system development and reproductive capabilities

  • Maintains blood pressure

    • Increases adrenergic receptors in blood vessels

Synthesis

• Thyroid gland stores hormone extracellularly in follicle lumen until triggered by TSH to release

• Seven steps involved in synthesis of TH:

Thyroglobulin is synthesized and discharged into follicle lumen

1. Iodide is trapped: iodide ions (I^–) are actively taken into cell and released into lumen

2. Iodide oxidized: electrons are removed, converting it to iodine (I₂)

3. Iodine is attached to tyrosine: mediated by peroxidase enzymes

4. Iodinated tyrosines link together to form T₃ and T₄

5. Colloid is endocytosed by follicular cells

• Vesicle is then combined with a lysosome

1. Lysosomal enzymes cleave T₃ and T₄ from thyroglobulin 

• Hormones are secreted into bloodstream

• Mostly T₄ secreted, but T₃ is also secreted

• T₄ must be converted to T₃ at tissue level

Transport and regulation

• T₄ and T₃ transported by thyroxine-binding globulins (TBGs) 

  • Both bind to target receptors, but T₃ is 10 times more active than T₄

  • Peripheral tissues have enzyme needed to convert T₄ to T₃

    • Enzyme removes one iodine

TH release is regulated by negative feedback

• Falling TH levels stimulate release of thyroid-stimulating hormone (TSH) 

  • Rising TH levels provide negative feedback inhibition on TSH

  • TSH can also be inhibited by GHIH, dopamine, and increased levels of cortisol and iodide

• Hypothalamic thyrotropin-releasing hormone (TRH) can overcome negative feedback during pregnancy or exposure to cold, especially in infants