Endocrine Thyroid VP Summer 2023 Ross University PDF

Cellular Biology & Homeostasis ENDOCRINE - THYROID VP Summer 2023 Clara Camargo, DVM 1. Locate the thyroid glands and briefly describe the macro and microanatomy of it 2. Understand the synthesis, regulation, transport and metabolic clearance of thyroid hormones 3. Describe the effects of th...

Cellular Biology & Homeostasis ENDOCRINE - THYROID VP Summer 2023 Clara Camargo, DVM 1. Locate the thyroid glands and briefly describe the macro and microanatomy of it 2. Understand the synthesis, regulation, transport and metabolic clearance of thyroid hormones 3. Describe the effects of the thyroid hormones on target tissues 4. Understand the symptoms of the main pathologies related to the thyroid hormones (hyperthyroidism, hypothyroidism and goiter) E N D O C RI NE S Y S T E M TERMINOLOGY Adenohypophysis Metabolic rate Albumin MIT (Monoiodotyrosine) Calcitonin Parafollicular cells (C-cells) Colloid T3 (Triiodothyronine) Cotransporter (symporter) T4 (Thyroxine) Deiodination Thyroglobulin DIT (Diiodotyrosine) Thyroid follicle Endocrinopathy Thyroid follicle lumen Endocytosis Thyroid Peroxidase Hormone clearance Thyrotropes Hypothalamus TRH Iodide TSH Iodine Tyrosine Lysosomes 4 ENDOCRINE SYSTEM HYPOTHALAMUS GHRH, CRH, TRH, GnRH, PRH Somatostatin Dopamine Pituitary gland ADENOHYPOPHYSIS GH THYROID ACTH T3 MSH T4 TSH Calcitonin FSH LH Prolactin NEUROHYPOPHYSIS Vasopressin/ADH Oxytocin PINEAL Melatonin PARATHYROID PTH ADRENAL GLANDS Aldosterone Cortisol Androgens Catecholamines OVARIES Estrogens Progesterone TESTICLES Testosterone PANCREAS Insulin Glucagon Somatostatin THYROID GLANDS - ANATOMY In most mammals, the thyroid glands are located caudal to the trachea at the level of the first or second tracheal ring ENDOCRINE SYST EM CHEMICAL STRUCTURE OF HORMONES ENDOCRINE SYST EM AMINES (Recall)  Derived from the amino acid tyrosine  Catecholamines (hydrophilic)  T3 and T4 thyroid hormones = hydrophobic Blood transport  Catecholamines circulate unbound in the blood  Thyroid hormones  Thyroxine-binding globulin (TBG) and albumin  produced by the liver  Half-life depends on the hormone  Thyroxine = 7-10 days  Epinephrine = 1 minute  Catecholamines bind to cell membrane receptors  Thyroid hormones bind to nuclear receptors THYROID GLAND ENDOCRINE SYST EM Thyroid tissue consists of numerous sac-like structures called thyroid follicles that vary in size • Follicular cells are arranged in a circular pattern  A single layer of epithelium  Synthesize the thyroid hormones THYROID GLAND The follicles are filled with colloid  Colloid: viscous protein rich liquid (thyroglobulin = glycoprotein)  The main storage of the thyroid hormones (active) • Within the lumen created by glandular cells • This form of storage allows mammals to withstand periods of iodine deprivation without an immediate effect on the production of thyroid hormones. Parafollicular cells or C-cells are located outside the follicles  Secrete calcitonin  One of the hormones that regulate calcium metabolism ENDOCRINE SYST EM THYROID GLAND ENDOCRINE SYST EM THYROID HORMONE SYNTHESIS (Thyrotropes) THYROID HORMONE SYNTHESIS 2 molecules of importance:  TYROSINE  IODINE (I2) TYROSINE is a part of a large protein called thyroglobulin (glycoprotein)  Thyroglobulin (TG) is synthesized within the follicle cell and secreted into the colloid  Contains a large number of tyrosine amino acid residues  Tyrosine is the major substrate that combines with iodine to form thyroid hormones ENDOCRINE SYST EM THYROID HORMONE SYNTHESIS Iodine (I2) comes from the diet  It gets converted to IODIDE (I-) in intestinal tract & transported to the thyroid follicle cells Thyroid follicle cells trap the iodide (I-) via an active transport process (Na+/I- cotransporter) • sodium provides the driving force to bring iodide Iinto the cell • Intracellular [iodide] is 25 – 200 x higher than outside of the cel ENDOCRINE SYST EM THYROID HORMONE SYNTHESIS ENDOCRINE SYST EM In the thyroid follicle lumen Thyroid Peroxidase (enzyme!) will facilitate:  Organification: Oxidation of iodide to iodine (I⁻→ I²) + Tyrosine iodination  Tyrosine iodination (Iodine combine to the tyrosine amino acid on thyroglobulin protein)  Tyrosyl ring can accommodate 2 iodine molecules  If 1 molecule attaches = MONOIODOTYROSINE (MIT)  If 2 molecules attach = DIIODOTYROSINE (DIT)  Coupling (fusion) of two of these iodinated tyrosines  1 DIT + 1 DIT = T4 or Tetraiodothyronine or Thyronine or Thyroxine  4 iodine molecules  1 MIT + 1 DIT = T3 or Triiodothyronine  3 iodine molecules THYROID HORMONE SECRETION ENDOCRINE SYST EM  T3 and T4 remain attached to thyroglobulin molecule and stored in the colloid until secretion o Unique type of storage (allows the thyroid to store a large reserve of the hormone)  T4 is the major hormone produced by the follicular cells o Only small amounts of T3 are produced by the thyroid gland o Major source of T3 is peripheral deiodination of T4 in target tissues (enzyme dependent) FYI Depending on the position of iodine, reverse T3 can be formed  Inactive form of the hormone Secretion process:  Produced during disease states in peripheral tissues • Endocytosis of iodinated thyroglobulin from the lumen into the follicle cell • Lysosomes fuse to thyroglobulin vesicle → enzymes cleave T3 and T4 • T3 & T4 are released and freely pass through the thyroid follicle cell membrane (lipophilic) into the blood stream THYROID HORMONE TRANSPORT Thyroid hormones are transported in plasma attached to proteins o Thyroxine-binding globulin (TBG) and o Albumin (both synthesized in the liver)  A small amount of hormone is free in the circulation o Free T4 and T3 are available to diffuse into the target cells o Once free T4 has entered the target cell, most of it will be converted to T3  By iodothyronine deiodinases in the cytosol ENDOCRINE SYST EM THYROID HORMONE TRANSPORT ENDOCRINE SYST EM The equilibrium between free and bound hormone in the blood plasma is easily shifted because of physiological or pharmacological situations • Such as the increase in estrogen concentrations that occurs during pregnancy Adjustments to maintain a normal amount of free hormone occur rapidly with:  A decline in the rate of metabolism or  Stimulation of thyroid hormone production through the release of thyroid-stimulating hormone (TSH) Reference values of free T4 and T3 will be different for different species HORMONE CLEARANCE ENDOCRINE SYST EM The rate of the removal of the hormone from the blood can be measured • It is called the METABOLIC CLEARANCE RATE • The metabolic clearance rate interferes with hormone concentrations MCR = RATE OF THE DISAPPEARANCE OF HORMONE FROM PLASMA CONCENTRATION OF HORMONE HORMONE CLEARANCE ENDOCRINE SYST EM T4 and T3 Hormones are “cleared” from the plasma in several ways  Conjugation (formation of sulfates and glucuronides mainly in liver and kidneys)  Deionization (metabolic breakdown by the tissues, mainly in liver, skeletal muscle and kidneys)  Excretion by the liver into the bile (than in the feces)  Excretion by the kidney into the urine A decreased metabolic clearance rate can cause an excessively high concentration of thyroid hormones in the blood  Ex: liver disease ACTIONS OF THYROID HORMONES Thyroid hormones are the primary factors for the control of metabolism o Bind to nuclear receptors and initiate the transcription of mRNA (protein synthesis!) o Are important for the normal metabolic activity of all tissues Physiological actions are not precisely determined o Most of the knowledge comes from the research with the diseases (hypo or hyperthyroidism) ENDOCRINE SYST EM ACTIONS OF THYROID HORMONES ENDOCRINE SYST EM  Increase numbers and activity of mitochondria o Increase the rate of formation of ATP • Could be due to increased activity of the cells  Increase the basal metabolic rate of cells o BMR = is the minimal rate of energy expenditure per unit time at rest  T3 regulates the activity and gene experssion of Na+/K+ ATPase o Calorigenic: ↑ O2 consumption of tissues ↑ heat production • Weight loss in hyper, weight gain in hypothyroidism Metabolic rate o Cellular enzymes increase the activity in response to thyroid hormones Thyroid hormones ACTIONS OF THYROID HORMONES ENDOCRINE SYST EM  Carbohydrate metabolism o Increasing intestinal glucose absorption and facilitating the movement of glucose into both fat and muscle o Probably secondary to the increase in cellular metabolic enzymes  Fat Metabolism o Enhance mobilization (β-oxidation), increase FFAs, increase lipolysis o Thyroid stimulation decreases plasma cholesterol and liver fat  Increase cellular uptake and degradation of LDL, increase cholesterol secretion in the bile o Hypothyroid individuals have hyperlipidemia and fatty liver ACTION OF THYROID HORMONES ENDOCRINE SYST EM  Growth & development are influenced by thyroid hormones o TH permit maturation of the nervous system (CNS)  If inadequate thyroid hormones: reduced mental abilities, lethargic o Work in conjunction with Growth Hormone (GH) The National Geographic Images  Increase blood flow and cardiac output o Possibly through interactions with catecholamines Health 24  Increase Heart rate o Direct effect on the excitability of the heart Balance me beautiful ACTION OF THYROID HORMONES ENDOCRINE SYST EM  GI effects o Increase appetite and food intake o Increase GI motility • Diarrhea → hypermotility  Thyroid-induced metamorphosis in amphibians Lumen- Boundless Biology ACTION OF THYROID HORMONES ENDOCRINE SYST EM Text fig. 2 Photograph taken August 6. A, Undersized thyroidless tadpole; B, large thyroidless tadpole with body length of 34.5 mm. The twist of the tail is abnormal. It is discussed in the text. C, a metamorphosed control; D,metamorphosed operated tadpole. Section of the head showed that there hadbeen incomplete removal of the thyroid gland. A sufficiently large thyroid gland had developed to produce metamorphosis THYROID REMOVAL IN LARVAE OF RANA PIPIENS BENNET M. ALLEN REGULATION OF THYROID HORMONES THROUGH NEGATIVE FEEDBACK LOOP FIG. 34.6 Hypothalamopituitary-thyroid axis. + signs indicate stimulation; signs indicate inhibition. T3, Triiodothyronine; T4, thyronine; TRH, thyrotropinreleasing hormone; TSH, thyroid-stimulating hormone. From Hedge GA, Colby HD, Goodman RL. Clinical Endocrine Physiology. Philadelphia: Saunders; 1987 ENDOCRINE SYST EM PATHOLOGIES ASSOCIATED WITH THE THYROID ENDOCRINE SYST EM HYPERTHYROIDISM Most common endocrinopathy of cats  Main cause is hyperplasia or tumors of the thyroid  Symptoms are related to hypermetabolism gland (thyroid adenoma)  weight loss  typically affects middle age to older cats  increased appetite (polyphagia)  is characterized by autonomous growth of thyroid follicles  increased thirst and urination (polydipsia and polyuria) (abnormality in the signal transduction of the thyroid cell  Vomiting, diarrhea  shedding and unkempt appearance  Hyperactivity, tachycardia Animal endocrine clinic PATHOLOGIES ASSOCIATED WITH THE THYROID HYPOTHYROIDISM ENDOCRINE SYST EM More common in dogs  Primary causes (strong breed disposition): Secondary causes:   lymphocytic thyroiditis (inflammation)  pituitary tumors  congenital thyroid dysgenesis (inherited defects in the  radiation therapy hypothalamic-pituitary-thyroid axis)  Glucocorticoids  T4 transport defects  Goitrogens, iodine deficiency  autoimmune thyroiditis  Symptoms: DogsAholic.com  lethargy and obesity (most common)  dull hair and truncal or tail alopecia, retention of puppy hair  reproductive disorders  constipation PATHOLOGIES ASSOCIATED WITH THE THYROID ENDOCRINE SYST EM IODINE DEFICIENCY IN CATTLE, SHEEP, GOATS - Goiter Iodine deficiency may be due to:  Inadequate dietary intake of iodine (i.e., Iodine deficiency typically results in enlargement of the thyroid glands (goiter). iodine deficient soils) or  Consumption of feeds containing Large firm, non-fluctuant, swelling of the compounds that either interfere with ventral neck in an otherwise healthy animal is iodine uptake by the thyroid gland or with likely to be goiter. normal synthesis of thyroid hormones (goitrogens) • Goitrogens – brassicas, white clover pastures E N D O C RI NE S Y S T E M DIAGNOSIS  Total T3 and T4  Free T4 Why do we need to understand: • Chemical structure of the hormones • Synthesis and regulation • How do they travel in the blood circulation • Signal transduction  T3 suppression test  Antibodies (T3 and T4, thyroglobulin)  TSH  Genetic test (TPO gene mutation)  Drugs affecting the thyroid hormones… • Hormone clearance HAPPY STUDYING Clara Camargo, DVM [email protected] ©2021 Ross University School of Veterinary Medicine. 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