Chapter 3-Thyroid Gland

1. Chapter 3-Thyroid Gland

2. Ch. 3-- Study Guide Critically read (1) pages pp. 43-50 before Metabolism of thyroid hormones section; (2) pages 56 (Regulation of thyroid hormone section) to the end of the chapter Comprehend Terminology (the text in bold/italic) Study and understand the text and corresponding figures.

3. 3.1. Introduction

4. § Introduction • Thyroid hormone: • required in every organ system • Thyroid hormone acts as a modulator • It plays an indispensable role in growth and development

5. 3.2. Morphology

8. § Morphology (1) • Location— right below the cricoid cartilage • Gross anatomy– 3 lobes; • Two large lateral lobes: • One pyramidal lobe: • Weight: 20g • Goiter: several hundred grams • Receives a greater/lesser (select one) flow of blood/lymph than most other tissues of the body • Receives abundant nerves of ANS

9. § Morphology (2) • Histology— Fig. 3.2 + x • The functional unit: follicle– epithelial cells (cuboidal or columnar) . . .—produces thyroid hormones • Glycoprotein colloid, inside the follicle, called thyroglobulin • A group of follicle forms a lobule surrounded by connective tissue (septum) • Parafollicular cells, C cells (between follicles– produce calcitonin

10. A C D B 1--Follicular cells; 2– colloid; 3– septum; 4– parafollicular cells

12. 3.3. Thyroid hormones

13. § Thyroid hormones • Structure--Amino acid derivatives of tyrosine (Fig. 3.3) • Thyroxine: more abundant • Triiodothyronine: less abundant, more potent

15. 3.3A. Biosynthesis of Thyroid hormones

16. § Iodine trapping • Made possible by iodide pump: • Sodium iodide symporter • Energy needed

17. § Thyroglobulin synthesis Steps of thyroglobulin movement: • Thyroglobulin (TG)– is a precursor of T3, T4 • Thyroglobulin is produced in the ribosomes • TG is released into the follicular lumen.

18. § Incorporation of iodine Iodide movement: • Diffusion throughout the follicular cell • Exit from the apical membrane by iodide transporters called pendrin • (Organification) Oxidized form of iodides is linked to thyroglobulin (TG) by thyroperoxidase (TPO) • This produces monoiodotyrosine (MIT) and diiodotyrosine (DIT); • (Coupling)--they may also become T3 and T4 pretty soon by TPO Fig. 3.4 & 3.5

20. Coupling of MIT and DIT to T4

21. § Storage and secretion of thyroid hormones • (Storage)– • At follicular lumens • MIT and DIT in thyroglobulin comprise 90% of the total pool of iodine in the body • (Secretion)– Endocytosis + exocytosis • (Endocytosis) TG is brought back into follicular cells • Long pseudopodia reach out from apical surfaces to “scoop up” TG (Fig. 3.6) • Endocytic vesicles migrate toward the basal membrane + meet with lysosome • (Exocytosis)– T4 and T3 (20:1) are released into the bloodstream; MIT and DIT reused in the cell. Fig. 3.4 again

23. 3.4. Control of thyroid function

24. § Effects of TSH • The principal regulator of thyroid function is the TSH (thyroid-stimulating hormone) • Pleiotropic physiology by TSH– on thyroid hormone biosynthesis and secretion, and increase blood flow to the thyroid. • (TSH receptors) TSH binds to G-protein-coupled receptors in ________ cells. • (Second messengers)– mainly through cAMP followed by protein kinase A; but also through diacylglycerol (DAG)/inositol-trisphosphate (IP3)

25. § Effects of thyroid-stimulating immunoglobulins • Hyperthyroidism– overproduction of thyroid hormone (Graves’ disease): • Extremely low of TSH in blood plasma • Yet the thyroid is under intense stimulation; why? (see below) • TSI (Thyroid-stimulating immunoglobulin) from the lymphocytes can bind to TSH receptors

26. § Autoregulation of thyroid hormone synthesis • Thyroid hormone production is blocked temporarily when the iodide in blood plasma becomes too high • Thyroglobulin also down regulates biosynthetic activity of the thyroid gland– this action is through down regulation of thyroglobulin, thyroid peroxidase, the sodium iodide symporter, and the TSH receptor

27. 3.5. Thyroid hormones in blood

28. § Three binding proteins • 99% of thyroid hormones binds to the following three proteins • Thyroxine-binding globulin (TBG)– binds to @ 70% of the total protein-bound hormone; why? • Transthyretin (TTR)—15% • Albumin—15%

29. Hydrophilic hormone Receptor in plasma membrane Target cell Transport protein Second- messenger activation Free hormones Bound hormone Hydrophobic hormone Receptor in nucleus Tissue fluid Blood 3-29

30. TBG Various metabolic effects T3 T4 Protein synthesis mRNA DNA T4 I T3 Blood Tissue fluid Target cell 3-30

31. 3.6. Regulation of thyroid hormone secretion

32. § Feedback mechanism of thyroid hormones • No TSH– thyroid cells are atrophy • Administer of TSH– increases thyroid hormones • Patients lack TSH receptors– hypothyroidism, no functional thyroid gland, and high levels of TSH • Feedback of thyroid hormones on both TRH and on thyrotropes Fig. 3.12 and 3.13

34. In Thyrotrope: --T3 on TRH and TSH; --TRH on TSH

35. Thyroid hormones (3-4 weeks) reduce the sensitivity of the thyrotropes to TRH

36. 3.7. Mechanism of thyroid hormone action

37. § Mechanism of thyroid hormone action • All cells require optimal amounts of thyroid hormone for normal operation • Thyroid hormone receptors are the nuclear receptor; however not completely understood • Details– • Thyroid hormone receptors bind to the gene they regulate no matter the hormone is present or not • Once binding T3, the configuration of the receptor is modified; corepressor is released and binds to a coactivator (Fig. 3.15)