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IDD Festival Medical Publication Editors Society 24-25 May-2010 Tehran-IR-Iran

Iodine and Thyroid Physiology. IDD Festival Medical Publication Editors Society 24-25 May-2010 Tehran-IR-Iran. Dr.S. Zahedi, PhD, Professor of Endocrine Physiology, Endocrine Research Center, Research Institute for Endocrine Sciences

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IDD Festival Medical Publication Editors Society 24-25 May-2010 Tehran-IR-Iran

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  1. Iodine and Thyroid Physiology IDD Festival Medical Publication Editors Society 24-25 May-2010 Tehran-IR-Iran Dr.S. Zahedi, PhD, Professor of Endocrine Physiology, Endocrine Research Center, Research Institute for Endocrine Sciences Shaheed Beheshti University of Medical Sciences, Tehran-IR-Iranzahedi@endocrine.ac.ir

  2. Iodine • AtomicNumber: 53 • Symbol: I • Atomic Weight: 126.90447 • Discovery: Bernard Courtois 1811 (France) • Melting point :of 113.5°C • Slightly soluble in water

  3. Evaporative salts .........................avg.                10 ppb (Roeber)Ocean ...................................................            50 ppb Igneous rocks ...............................avg.             100 ppb (R. Fuge)Average Crustal Content ...................               300 ppb (Manson)Sedimentary rocks .......................avg.            1800 ppb (Itkina, Lygalova)Soils ............................................avg.            4800 ppb (Goudge, 260,000 + soil samples)

  4. Sources • Iodine is primarily retrieved from underground brines (water with many dissolved salts and ions) that are associated with natural gas and oil deposits. • It is also retrieved as a by-product with nitrate deposits in caliche deposits. Chile’s production of iodine is from this source.

  5. Seawater contains 50 ppm (parts per million) iodine which means that there are approximately 76 billion pounds of iodine in the world’s oceans. • Iodine was first discovered in seaweed. • Dried seaweeds, particularly those of the Liminaria family, contain as much as 0.45% iodine.

  6. Seaweed was a major source of iodine before 1959. • Seaweed is a significant source for iodine in the diets of many people around the world. • Production from caliche is presently the most economical of the options listed here

  7. "The basic source of iodine in soils is iodine of the atmosphere.“ • " The ocean is the reservoir from which all of the iodine of the atmosphere is drawn"

  8. Seafood • Cod • Sea bass • Haddock • Perch • Kelp • Dairy products • Plants grown in soil rich in iodine

  9. In each 100 gr • Iodized Salt 3000 mcg • Cereals and Breads 10-11 mcg • Meat 26-27 mcg • Vegetables 32-33 mcg • Fruits 25-70 mcg • Haddock Almost 300 mcg • Malt bread29-30 mcg • Jaffa cakes More than 32 mcg • Cod More than 90 mcg • Boiled Egg 1 egg 23.76 mcg • Mayonnaise 35-36 mcg

  10. The highest iodine content is found in brown algae, with dry kelp ranging from 1500-8000 ppm (parts per million) and dry rockweed (Fucus) from 500-1000 ppm. • In most instances, red and green algae have lower contents, about 100-300 ppm in dried seaweeds, but remain high in comparison to any land plants.

  11. Daily adult requirements, currently recommended at 150 µg/day, could be covered by very small quantities of seaweed. • Just one gram of dried brown algae provides from 500-8,000 µg of iodine • Even the green and red algae (such as the purple nori that is used in Japanese cuisine) provides 100-300 µg in a single gram.

  12. Iodine absorption • Oral.  Iodine appears to be inactivated by combination with gastrointestinal contents. Absorption is poor due to rapid conversion of iodine to iodide.  (Reynolds, 1989; Gilman et al., 1990). • "Inhalation.  Iodine is absorbed from the lungs, converted to iodide in the body, (ILO 1971). Pulmonary absorption of vapour may result in systemic poisoning (Gosselin et al., 1984).

  13. Absorption……. "Dermal. Only very small quantities of iodine are absorbed through an  intact skin, (Reynolds, 1989). • Iodine can be absorbed by wounds and abrasions. • Enhanced absorption occurs through denuded skin, decubitus ulcers, mucosal surfaces with high absorptive capacity , or large areas of intact skin, (Dela Cruz et al., 1987; Vorherr et al., 1989; Prager & Gardner 1979; Cosman et al., 1988).  • "Eye.  Iodine can be absorbed when applied on the eye, (Geisthoevel, 1984).

  14. Iodine secretion • Iodine is secreted in saliva, other gastrointestinal fluids, and breakdown of iodine from hormones is reabsorbed in the digestive tract • Intestinal parasitic infestations interfere with iodine absorption

  15. Iodine Absorption • The question of where and how dietary I is absorbed in the gastrointestinal tract has long been of major interest. • Reports on the absorption of I in the intestine appeared as early as 1912 . • In the 1950s, some authors suggested that I might be both absorbed from and secreted to the intestinal lumen. • Passive or simple diffusion of iodide from the intestinal lumen to the bloodstream was believed to be the mechanism in iodide absorption.

  16. Iodine transport • Active I- accumulation in the thyroid is mediated by the Na+/ I- symporter (NIS), a plasma membrane glycoprotein • Using as its driving force the Na+ gradient generated by the Na+_-K+_-ATPase, NIS couples the inward movement of Na+ in favor of its concentration gradient to the inward movement of I- against its electrochemical gradient. Characteristic hallmarks of • Characteristic hallmarks of NIS are its Na dependence

  17. NIS mediates I uptake in several tissues besides the thyroid, including : • Lactating mammary gland, • Gastric mucosa, • & salivary glands • It appears that Na+/ I- symporter is present in GI tract small intestine)

  18. Pyramidal lobe About 20 gr In women> men Composed of follicles

  19. Originate from endoderm of primitive pharynx Innervation: Sympathetic Parasympathetic Peptidergic VIP NPY Sub. P Galanin Originate from neural crest

  20. Thyroid Cells • Tight Junctions • Adherent junctions • Desmosome junctions =================== • Gap junctions • Polarity Besolateral K-Na ATPase TSH receptors Na-I Symporter Apical Microvilli Ability to form Pseudopods Peroxidase Aminopeptidase H2O2 generating capacity --------------------------------------- polarity is also indicated by organelles

  21. Function of Thyroid Cells: • Concentration of Iodine • Synthesis of Tg • Synthesis of TPO • H2O2 generation • Re-absorption of iodinated Tg • Degradation of iodinated Tg • ============================ • Hormone synthesis and secretion

  22. Against gradient of charge and concentration Pendrin -5-mv Passive diffusion can restore thyroid function But 50-100 fold iodine intake is nec.

  23. THYROGLOBULIN • Code for synthesis in human Ch. 8, rat Ch. 7 • 2 subunit 330 KDa each • Carbohydrate 8-10%, Mannose, Galactose, N-acetylglucosamine, Sialic Acid, Fucose • Idoinated form • Dimmer • .2-1% iodine

  24. H2O2 production NADPH Oxidase H2O2 NADPH Oxidase Electron acceptor O2 H2O2 H2O2 O2 2O2- NADP+ NADPH NADP+ NADPH Ca2+ Superoxide dismotase (SOD)

  25. Hormone synthesis

  26. Thyroid Hormone Secretion • Pinocytosis, Macro( up to 3 um), Micro (100-200nm) • Colloid droplets, receptor mediated, low affinity • Lysosomes (0.1-1 um) containing hydrolytic enz( proteolytic). Active at Acidic pH <6 • Aspartic proteinase, CathepsinD • 2 Cystein proteinase Cath. L & B

  27. r= 1 T4/T3 effluent r=.5 T4/T3 in thyroid

  28. Thyroxine Binding Globulin • 54 KD • Acidic Glycoprotein (20%) 1 binding site • Asso. Constant 1*1010 (T4) • Asso. Constant 1*109 (T3) • X chromosome • In Euthyroid subjects 1/3 is occupied • Fully saturated 20 ug/dL • Half life ~ 5 days • Est incraese HL due to increase of the number of sialic acid

  29. Thyroxine Binding Pre albumin( Transthyretin TTR) • 55 KD Tetramer • Each 127 AA • 1 T4 per mol • Chromosome 18 • Half life ~ 2 days • It forma a complex with Retinol Binding Protein: Stabilize the protein

  30. Albumin • 66.5 KD Tetramer • 585 AA • Several binding site but only 1 has high affinity • Chromosome 4 • Half life ~ 15 days

  31. Receptors • T3 receptors are nuclear proteins of 400–500 amino acids containing several functional domains, especially the ligand and the DNA binding domains. • There are two receptor genes, designated TRa and TRb, located in different chromosomes. • Types α1 , 2, & 3 Gen located at ch. 17 • Types β1 , 2, &3Gen located at ch. 3 • They encode nine protein products that arise by alternative splicing and differential promoter usage.

  32. Thyroid hormone • Metabolic • Thermogenic • Carbohydrate metabolism • Protein metabolism • Fat metabolism • Effect on organs • Cardiovascular system • Respiratory system • Central system

  33. Thyroid hormones Metabolic effects

  34. Thyroid hormones Metabolic effects • Heat production • Increased metabolism • Increased Na-K ATPase activity • Increased synthesis of uncoupling protein in adipose tissue

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