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THYROID PHYSIOLOGY

THYROID PHYSIOLOGY. Jack L. Leonard, Ph.D. office: S4-100L2B phone: X66687 email: jack.leonard@umassmed.edu http://users.umassmed.edu/jack.leonard. THE THYROID GLAND. www.univ-st-etienne.fr/lbti/Mednucl/AtlasEnd/thyroide/. THYROID GLAND HISTOLOGY.

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THYROID PHYSIOLOGY

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  1. THYROID PHYSIOLOGY Jack L. Leonard, Ph.D. office: S4-100L2B phone: X66687 email: jack.leonard@umassmed.edu http://users.umassmed.edu/jack.leonard

  2. THE THYROID GLAND www.univ-st-etienne.fr/lbti/Mednucl/AtlasEnd/thyroide/

  3. THYROID GLAND HISTOLOGY http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html

  4. THYROID FOLLICULAR CELL MORPHOLOGY

  5. OH OH I I I I I O O NH2 NH2 I I OH OH O O 3,5,3’-Triiodothyronine (T3) THYROID HORMONES Thyroxine (T4)

  6. FEEDBACK REGULATION THE HYPOTHALAMIC-PITUITARY-THYROID AXIS • Hormones derived from the pituitary that regulate the synthesis and/or secretion of other hormones are known astrophic hormones. • Key players for the thyroid include: TRH - Thyrophin Releasing Hormone TSH - Thyroid Stimulating Hormone T4/T3 - Thyroid hormones

  7. PITUITARY-THYROID AXIS – – + HM Goodman, BASIC MEDICAL ENDOCRINOLOGY 3rd Ed.

  8. PITUITARY-THYROTROPE CELL HM Goodman, BASIC MEDICAL ENDOCRINOLOGY 3rd Ed.

  9. TSH REGULATION OF THYROID FUNCTION • TSH binds to specific cell surface receptors that stimulate adenylate cyclase to produce cAMP. • TSH increases metabolic activity that is required to synthesize Thyroglobulin (Tg) and generate peroxide. • TSH stimulates both I- uptake and iodination of tyrosine resides on Tg.

  10. ClO4-, SCN- organification NaI symporter (NIS) Propylthiouracil (PTU) blocks iodination of thyroglobulin Thyroid peroxidase (TPO) ION TRANSPORT BY THE THYROID FOLLICULAR CELL BLOOD I- COLLOID I-

  11. Iodination of Tyr residues of Tg TSH TSH receptor TPO THYROGLOBULIN SYNTHESIS IN THE THYROID FOLLICULAR CELL COLLOID

  12. T4 T3 DIT MIT I- TSH TSH receptor THYROID HORMONE SECRETION BY THE THYROID FOLLICULAR CELL COLLOID

  13. THYROID HORMONES IN THE BLOOD • Approximately 99.98% of T4 is bound to 3 serum proteins: Thyroid binding globulin (TBG) ~75%; Thyroid binding prealbumin (TBPA or transthyretin) 15-20%; albumin ~5-10% • Only ~0.02% of the total T4 in blood is unbound or free. • Only ~0.4% of total T3 in blood is free.

  14. NH2 NH2 I OH I OH OH “Step up” “Step down” I O O O I T4 I I OH I R OH I R I O O I T3 rT3 I OH I R O 3,3’-T2 R = THYROID HORMONE METABOLISM

  15. THYROID HORMONE DEIODINASES • Three deiodinases (D1, D2 & D3) catalyze the generation and/disposal of bioactive thyroid hormone. • D1 & D2 “bioactivate” thyroid hormone by removing a single “outer-ring” iodine atom. • D3 “inactivates” thyroid hormone by removing a single “inner-ring”iodine atom. • All family members contain the novel amino acid selenocysteine (SeC) in their catalytic center.

  16. extracellular domain A B E intracellular domain COOH D C NH2 EXISTS AS A DIMER BASIC ORGANIZATION OF THE SELENODEIODINASES

  17. BASICS OF THYROID HORMONE ACTION IN THE CELL

  18. STEROID/THYROID HORMONE FAMILY OF NUCLEAR RECEPTORS

  19. SPECIFIC ACTIONS OF THYROID HORMONE: METABOLIC • Regulates of Basal Metabolic Rate (BMR). • Increases oxygen consumption in most target tissues. • Permissive actions: THincreases sensitivity of target tissues to catecholamines, thereby elevating lipolysis, glycogenolysis, and gluconeogenesis.

  20. SPECIFIC ACTIONS OF THYROID HORMONE: DEVELOPMENT • TH is critical for normal development of the skeletal system and musculature. • TH is also essential for normal brain development and regulates synaptogenesis, neuronal integration, myelination and cell migration. • Cretinism is the term for the constellation of defects resulting from untreated neonatal hypothyroidism.

  21. EXAMPLES OF THYROID DISEASES Hyperthyroidism 1° Hypothyroidism www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

  22. EXAMPLES OF THYROID DISEASES Juvenile Hypothyroidism Congenital Hypothyroidism www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

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