THYROID HORMONE — SA OE EAN a METTHYROID GLAND Location: The thyroid gland located below the larynx on each side of and anterior to the trachea. ~ Largest Endocrine Hormone Secretion: * secretes: 1. thyroxine (T4) 2. triiodothyronine (T3) 3. Also secretes calcitonin (an important hormone for calcium metabolism) Cell: Thyrotopes » secretion is controlled by thyroid-stimulating hormone (TSH) from the anterior O 93% T4 & 7% T3 T4-T3 in tissues Qualitatively same Differ in Rapidity & Intensity of action. T3 is 4 times more potent than T4, but decrease cone. In blood & decrease half life. T3 and T4 combine mainly with thyroxine-binding globulin. More than 90% of Thyroid hormone that binds with cellular receptors is T3. eae eeThyroid Hormones Have Slow Onset and Long Duration of Action { > 14 No effect for 2-3 days after injection Long Latent Period. Activity peaks in 10-12 days & || with a half life of 15 days. In some cases it takes 6 weeks-2 months. > 13 4 times rapid Latent Period 6-12 hours Peak in 2-3 daysPhysiologic Anatomy of the Thyroid Gland. ¢ Composed of large numbers of closed follicles filled with colloid and lined with cuboidal epithelial cells that secrete into the interior of the follicles ¢ The major component of colloid is the large glycoprotein Thyroglobulin contains the thyroid hormones within its molecule.Iodine Requirement * 50mg/year, 1mg/week O + Ingested iodine in the form of iodides + lodides ingested orally are absorbed from GIT * ¥% removed from the blood by thyroid cells for synthesis of hormones; rest excreted through kidneys. - Basal membrane of thyroid cells has an active pump to push iodides to interior (Iodine Pump). Normally 30% more conc. Inside — Max. active 250% more conc. Inside + The rate of lodine trapping is influenced by conc. of TSH + TSH stimulates and hypophysectomy greatly diminishes the activity of the iodide pump in thyroid cells.‘Thyroid cellular mechanisms for iodine transport, thyroxine and triiodothyronine formation, and hyroxine and triiodothyronine release into the blood. O + lodination — @ —_—_——>1,_ and Peroxidase ‘coupling ” MIT DIT peering = el — Pinocytesis “T, MIT, monoiadotyrosine; DIT, diiodotyrosine; T3, triiodothyronine; T4, thyroxine; TG, thyroglobulSynthesis of Thyroid Hormone O 1, Formation and Secretion of 2. Iodide Trapping Thyroglobulin Thyroglobulin . *Transport of iodides from the *ER and Golgi apparatus blood in to the thyroid follicles. synthesize and secrete in to the eek : i follicles a large glycoprotein This is achieved by the action of molecules called “Thyroglobulin” sodium-iodide symporter (NIS) eWhich cotransport one iodide ion along with two sodium ions. eNa-K ATPase pump. This | process is called iodide Trapping. eEach mol. Of Thyroglobulin contain 70 tyrosine amino acids . Tyrosine + Iodide = Thyroid hormone within Thyroglobulin.Synthesis of Thyroid Hormone 3. Conversion of Iodides to 4. lodination oxidized form of Iodine Combination of iodine with *Oxidized form of iodine is capable tyrosine is called iodination. of combining directly with amino acid Tyrosine. Oxidation is promoted by enzyme Peroxidase & Heaeean Danie (H202) Peroxidase is in apical membrane of the cell or attached to it . eThyroglobulin mol. comes out of Golgi & cell membrane at the same place. If Peroxidase is not pened hormone formation falls to zero.Synthesis of Thyroid Hormone O 5. Organification: Binding of oxidized Iodine with Thyroglobulin. Enzyme Iodinase speeds up the reaction. Tyrosine is first iodized to Monoidotyrosine then Diidotyrosine. T3 =1molecule of monoidotyrosine +1 molecule of Diidotyrosine. T4 =1 molecule of Diidotyrosine. +1 molecule of Diidotyrosine RT3 (REVERSE T3) = Coupling of Diidotyrosine + monoidotyrosineStorage of Thyroid Hormone. a O After synthesis of thyroid hormone, each Thyroglobulin mol. has 30 thyroxine molecules and a few T3. Storage sufficient for 2-3 months.Release of Thyroxine and Triiodothyronine in the blood Cleavage required for the release. + Pseudopod extensions from the apical surface of the thyroid cells that close around small portions of the colloid — pinocytic vesicles formed— enter the apex of thyroid cell __proteases . digestive vesicles lysosomes. release T4 & T3 in free form— diffuse through the base of the thyroid cell into the blood. 34 of iodinated tyroxinase never forms hormone, remains as mono or di ido-MIT, DIT released from Thyroglobulin deiodinase, Tyrosine + I-. Fetpemase, 75% MIT, DIT is recycled. = |1) of enzyme deiodinase can cause defficiency of hormones due to lack recycling. Hormone used by tissues is Triidothyroxine 35 ngm/day. « 99% of Tg & T4 combines with plasma proteins on entering blood. _ Thyroxine binding globulin mainly ~ Thyroxine binding prealbumins - Thyroxine binding albuminFunctions of the Thyroid Hormones 1. Genomic Effect Effect of Thyroid Hormone on Sexual ‘Thyroid Hormones Increase the Function Transcription of Large Numbers of Genes nanan 2. Effect on Body Tissue i + Lack of Thyroid hormone—Loss Increased Basal Metabolic Rate of libido Increased Respiration Increased Gastrointestinal Motility « Hyperthyroidism often results in - Great excess of Thyroid hormone—+Impotence diarrhea. In women * Lack of thyroid hormone can cause «lack of thyroid hormone— Loss of constipation. a libido Increase eerebration. Hyperthyroidism — si extreme nervousness & psychoneurotic | ~ Hypothyroidism often causes tendencies e.g anxiety complexes, extreme menorrhagia and polymenorrhea worry & paranoia | but strangely enough, in some 3. Effect on CVS | women it may cause irregular Increased blood flow parla andl Goeusibablly ever Increased Cardiae output amenorrhea. Increased Heart rate aa - hyperthyroidism— eeescedl inva etrene te oligomenorrhea and occasionally amenorrheaEffect on Protein Metabolism Protein formation }t& protein catabolismt? as well (Anabolic + Catabolic effect). Effect on Carbohydrate Metabolism + Uptake of glucose by cells Enhanced glycolysis Enhanced glyconeogenesis +Rate of absorption from GIT Insulin secretion Fat Metabolism; Increase Lipid mobilization from fat tissue Decrease Plasma cholesterol, phospholipids, triglycerides Effect on Sleep ~ Inhyperthyroidism the exhausting effect of thyroid hormone on the musculature and on the central nervous system —a feeling of constant tiredness. excitable effects on synapses do not let person sleep. - Hypothyroidism Extreme somnolence with sleep sometimes lasting 12-14 hrs/day. aRegulation of thyroid secretion. CO) Hypothalamus peat, x (? increased temperature) zi . 7 *, (Thyrotropin-releasing hormone) £ Anterior pituitary 7 ' ry | Inhibits \ 1 ‘ \ trophy ‘eo id lodineAntithyroid Substances O e Antithyroid substances supress Thyroid secretion * Thiocyanate Ions Decrease Iodide Trapping ° Propylthiouracil Decreases Thyroid Hormone Formation. * Iodides in High Concentrations Decrease Thyroid Activity and Thyroid Gland Size.Abnormalities of Thyroid Gland ° Hyperthyroidism: Increased rate of secretions of Thyroid Hormone. 1, Graves’ disease: Autoimmune disease Antibodies; ¢ Thyroid-stimulating immunoglobulins (TSIs) against TSH receptors . TSIs bind with TSH receptors in TG. and cause continuous activation of cell | Increased sweating, Weight lo: ¢ Thyroid adenoma: Tumor in thyroid tissue Secretes large quantities of TH. ~General symptoms of hyperthyroidism: High excitability, Intolerance to heat, Muscle weakness, Nervousne: Inability to sleep, Hand tremor, xophthalmos “atigue, T3&:T4 increases. TSH decreasesHypothyroidism: 1. Hashimoto disease: . Autoimmunity develops which destroys the gland 2. Thyroiditis and fibrosis 3. Endemic goiter: . Lack of iodine prevents formation of T4 and T3 . No inhibition of TSH secretion . TSH stimulates the thyroid cells to secrete high amount of thyroglobulin into follicles from the colloid . Ultimately enlargement of the gland oceursMyxedema: O « .Total lack of Thyroid Gland function . Non pitting edema due to Excessive interstitial gel formation by Protein bound hyaluronic acid and chondroitin sulfate . Bagginess under eyesand face swellingCretinism O Extreme hypothyroidism during | ~ Occasionally the tongue fetal life, infancy or childhood becomes very large in relation Characterized by failure of body to the skeletal growth + growth & by mental retardation. obstructs swallowing and breathing— guttural Mental retardation breathing that sometimes Skeletal growth in the child with Cretinism is characteristically more inhibited than is soft tissue growth-> disproportionate rate of growth (the _ soft tissues are likely to enlarge | excessively, giving the child with cretinism an obese, stocky, and short appearance).