Thyroid Physiology Page 2

Regulation of Thyroid Function:
- Thyroid-pituitary System
1. Hypothalamic cells secrete thyrotropic-releasing hormone (TRH)
  - TRH: tripeptide; binds to high affinity thyrotropic cell plasma membrane receptors
  - activates adenyl cyclase system or initiates calcium influx, promoting TSH release
  - In addition to enhancing TSH release, TRH increases TSH synthesis
2. TRH: secreted into the pituitary (hypophyseal) portal vein system
3. TRH (in the pituitary) stimulates synthesis and release of thyroid-stimulating hormone (TSH)
  - TSH: suprathyroid mediator
    - glycoprotein, secreted by basophilic (thyrotropic) anterior pituitary cells
    - TSH: stimulates thyroidal hypertrophy and hyperplasia
    - increases rate of thyroidal intermediary metabolism
    - increases nucleic acid and protein synthesis rates (including thyroglobulin)
4. TSH stimulates (through thyroidal adenylyl cyclase) increased synthesis and release of T₄ and T₃.
  - Physiological inhibitors of TSH secretion:
    - somatostatin, dopamine
5. T₄ and T₃ by negative feedback, act:
  - at the pituitary -- to block TRH effects
  - at the hypothalamus -- to inhibit TRH synthesis and secretion
return to main menu
- Thyroidal Autoregulation:
  - Self-regulation of iodide uptake (independent of TSH)
  - Mechanisms depend on blood iodine levels
    - Large iodine concentrations inhibits iodide organification
    - This mechanism can cause pathologic inhibition of thyroid hormone synthesis and therefore hypothyroidism (Hashimoto's thyroiditis)
  - Changes in thyroid organic iodine content causes changes (reciprocal) in:
    - iodide transport
    - growth
    - amino acid uptake
    - glucose metabolism
    - nucleic acid synthesis
  - Most important effect: Modification of response to TSH:
    - iodine:enrichment -- inhibiting
    - iodine:depleting-- enhancing
    - Mechanism of Action: probably by affecting cAMP production following TSH stimulation
return to main menu
- Non-Physiological Thyroid Simulation:
  - Graves' disease:
    - lymphocytes: release TSH receptor-stimulating antibody (TSH-R Ab [stim]) {thyroid-stimulating immunoglobulin}
    - TSH-R Ab [stim] binds to the TSH receptor and activates the thyroid
      - Duration of activation is longer than with physiological TSH

return to main menu