Dr. Omary Chillo (MD, PhD) The Thyroid Hormones 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 17/09/2018 Dr. Omary Chillo (MD, PhD)

Follicular Cells of the Thyroid Gland Colloid Capillaries Thyroid Follicle 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) TSH Gs Protein Enzyme Adenyl Cyclase ATP Activated cAMP Thyroxine 17/09/2018 Dr. Omary Chillo (MD, PhD)

Follicular Cells Hormones Secreted by the Thyroid Gland Follicular cells/Cuboidal epithelial cells Colloid Thyroid Follicle 93% Thyroxine/ Tetraiodothyronine (T4) T3 is 4 times more potent than T4 Follicular Cells 7% Triiodothyronine (T3) Para follicular cells Calcitonin 17/09/2018 Dr. Omary Chillo (MD, PhD)

Synthesis and secretion of Thyroid Hormones Colloid contains thyroglobulin 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Colloid Na+/I- symporter Na+ I- Capillaries 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) MIT DIT Iodinated Thyroglobulin I2 Peroxidase I- 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Iodinated Thyroglobulin I I MIT DIT DIT I I I I I I T3 Thyroxine T4 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Thyroid Follicles 17/09/2018 Dr. Omary Chillo (MD, PhD)

Why is Iodine Important in Thyroid Hormone Production? Thyroid hormones are unique biological molecules in that they incorporate iodine in their structure. Thus, adequate iodine intake (diet, water) is required for normal thyroid hormone production. Major sources of iodine: - iodized salt - iodated bread - dairy products - shellfish Minimum requirement: 75 micrograms/day 17/09/2018 Dr. Omary Chillo (MD, PhD)

Transport of Thyroid Hormones Thyroid hormones are lipid-soluble Thus, they are found in the circulation associated with binding proteins: - Thyroid Hormone-Binding Globulin (~70% of hormone) - Pre-albumin (transthyretin), (~15%) - Albumin (~15%) Less than 1% of thyroid hormone is found free in the circulation. 17/09/2018 Dr. Omary Chillo (MD, PhD)

One Major Advantage of this System The thyroid gland is capable of storing many weeks worth of thyroid hormone (coupled to thyroglobulin). If no iodine is available for this period (about 3 months), thyroid hormone secretion will be maintained. 17/09/2018 Dr. Omary Chillo (MD, PhD)

Autoregulation of Thyroid Hormone Production The rate of iodine uptake and incorporation into thyroglobulin is influenced by the amount of iodide available: - low iodide levels increase iodine transport into follicular cells - high iodide levels decrease iodine transport into follicular cells Thus, there is negative feedback regulation of iodide transport by iodide. 17/09/2018 Dr. Omary Chillo (MD, PhD)

Action of TSH on the Thyroid TSH acts on follicular cells of the thyroid. increases iodide transport into follicular cells increases production and iodination of thyroglobulin increases endocytosis of colloid from lumen into follicular cells

Regulation of TSH Release from the Anterior Pituitary TSH release is influenced by hypothalamic TRH, and by thyroid hormones themselves. Thyroid hormones exert negative feedback on TSH release at the level of the anterior pituitary. - inhibition of TSH synthesis - decrease in pituitary receptors for TRH 17/09/2018 Dr. Omary Chillo (MD, PhD)

Actions of Thyroid Hormone Required for GH action Increases intestinal glucose reabsorption (glucose transporter) Increases mitochondrial oxidative phosphorylation (ATP production) Induces enzyme synthesis Result: stimulation of growth of tissues and increased metabolic rate. Increased heat production (calorigenic effect) 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormone on Nutrient Sources Effects on protein synthesis and degradation: -increased protein degradation at high thyroid hormone levels (high metabolic rate; energy) Effects on carbohydrates: - high doses increase glycogen breakdown (high metabolic rate; glucose production) 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormones on the Cardiovascular System Increase heart rate Increase force of cardiac contractions Increase stroke volume Increase Cardiac output Up-regulate catecholamine receptors 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormones on the Respiratory System Increase resting respiratory rate Increase minute ventilation Increase ventilatory response to hypercapnia and hypoxia 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormones on the Renal System Increase blood flow Increase glomerular filtration rate 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormones on Intermediary Metabolism Increase glucose absorption from the GI tract Increase carbohydrate, lipid and protein turnover Down-regulate insulin receptors Increase substrate availability 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects Thyroid Hormones in Growth and Tissue Development Increase growth and maturation of bone Increase tooth development and eruption Increase growth and maturation of epidermis,hair follicles and nails Increase rate and force of skeletal muscle contraction Inhibits synthesis and increases degradation of mucopolysaccharides in subcutaneous tissue 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormones on the Nervous System Critical for normal CNS neuronal development Enhances wakefulness and alertness Enhances memory and learning capacity Required for normal emotional tone Increase speed and amplitude of peripheral nerve reflexes 17/09/2018 Dr. Omary Chillo (MD, PhD)

Effects of Thyroid Hormones on the Reproductive System Required for normal follicular development and ovulation in the female Required for the normal maintenance of pregnancy Required for normal spermatogenesis in the male 17/09/2018 Dr. Omary Chillo (MD, PhD)

Diseases of the thyroid Hyperthyroidism Secret 5 -15 times of normal Thyroxine hormone Thyroid gland increases in size Increases BMR > 50-100% The most common cause is an autoimmune disease called Graves’ disease Exophthalmos 17/09/2018 Dr. Omary Chillo (MD, PhD)

Diseases of the thyroid Hypothyroidism Reduced Thyroxine hormone production Thyroid gland increases in size Decreases BMR The most common cause is insufficient Iodine, lack of TH receptors, and lack of TH transport proteins Thyroid Goitre 17/09/2018 Dr. Omary Chillo (MD, PhD)

How is Goiter Related to Hyperthyroidism? Due to excessive stimulation by TSH (thyroglobulin production, enlarged follicles…). In this case, excessive stimulation of the thyroid gland by TSH DOES result in thyroid hormone secretion, since iodine is available. 17/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Thanks 17/09/2018 Dr. Omary Chillo (MD, PhD)