Thyroid Hormone Production:
The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism. Iodine is necessary for the production of T3 and T4. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as goitre. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. The ratio of T4 to T3 released into the blood is roughly 20 to 1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5′-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production.
Function of Thyroid Hormones:
The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neuronal maturation, and increase the body’s sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
Thyroid hormone leads to heat generation in humans. However, the thyronamines function via some unknown mechanism to inhibit neuronal activity; this plays an important role in the hibernation cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature.
THYROID HORMONE PRODUCTION:
Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland. The effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues). T3 is 3- to 5- fold more active than T4.
Thyroxine (3,5,3′,5′-tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as TBG), which is cleaved by enzymes to produce active T4.
The steps in this process are as follows:
- The Na+/I- symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodine ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I- against its concentration gradient.
- I- is moved across the apical membrane into the colloid of the follicle.
- Thyroperoxidase oxidises two I- to form I2. Iodide is non-reactive, and only the more reactive iodine is required for the next step.
- The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid.
- Thyroid-stimulating hormone (TSH) released from the pituitary gland binds the TSH receptor ( a Gs protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
- The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.
- These vesicles are then exocytosed, releasing the thyroid hormones.
Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine (T4) contains four iodine atoms. Triiodothyronine (T3) is identical to T4, but it has one less iodine atom per molecule.
Iodide is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium is cotransported with iodide from the basolateral side of the membrane into the cell and then concentrated in the thyroid follicles to about thirty times its concentration in the blood. Via a reaction with the enzyme thyroperoxidase, iodine is bound to tyrosine residues in the thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one particle of MIT and one particle of DIT produces triiodothyronine.
- DIT + MIT → r-T3 (biologically inactive)
- MIT + DIT → triiodothyronine (usually referred to as T3)
- DIT + DIT → thyroxine (referred to as T4)
Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically active agents central to metabolic regulation.
Thyroxine is believed to be a prohormone and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase. Deficiency of deiodinase can mimic an iodine deficiency. T3 is more active than T4 and is the final form of the hormone, though it is present in less quantity than T4.
EFFECT OF THYROXINE:
- Increases cardiac output
- Increases heart rate
- Increases ventilation rate
- Increases basal metabolic rate
- Potentiates the effects of catecholamines (i.e. increases sympathetic activity)
- Potentiates brain development
- Thickens endometrium in females
- increase metabolism of proteins and carbohydrates (i.e. they have a catabolic action)
Both excess and deficiency of thyroxine can cause disorders.
- Hyperthyroidism (an example is Grave’s Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men. Thyrotoxicosis is often used interchangeably with hyperthyroidism, but there are subtle differences. Although thyrotoxicosis also refers to an increase in circulating thyroid hormones, it can be caused by the intake of thyroxine tablets or by an over-active thyroid, whereas hyperthyroidism refers solely to an over-active thyroid.
- Hypothyroidism (an example is Hashimoto’s thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
- Clinical depression can sometimes be caused by hypothyroidism. Some research has shown that T3 is found in the junctions of synapses, and regulates the amounts and activity of serotonin, norepinephrine, and γ-aminobutyric acid (GABA) in the brain.
Preterm births can suffer neurodevelopmental disorders due to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet their postnatal needs.
CLICK HERE to watch a video tutorial on Grave’s Disease
References for Thyroid hormone Production:
- ^ References used in image are found in image article in Commons:Commons:File:Thyroid_systbcvhxcxcfffgem.png#References.
- ^ Chapter 48, “SYNTHESIS OF THYROID HORMONES” in: Walter F., PhD. Boron (2003).Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. p. 1300.ISBN 1-4160-2328-3.
- ^ How Iodide Reaches its Site of Utilisation in the Thyroid Gland – Involvement of Solute Carrier 26A4 (Pendrin) and Solute Carrier 5A8 (Apical Iodide Transporter) – a report by Bernard A Rousset. Touch Brieflings 2007
- ^ a b Page 493 (Table 33-3) in: Eugster, Erica A.; Pescovitz, Ora Hirsch (2004). Pediatric endocrinology: mechanisms, manifestations and management. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-4059-2.
- ^ Zoeller RT (April 2003). “Transplacental thyroxine and fetal brain development”. J. Clin. Invest. 111 (7): 954–7. doi:10.1172/JCI18236. PMC 152596.PMID 12671044.
- ^ “Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability.” Georg Hennemann, Roelof Docter, Edith C. H. Friesema, Marion de Jong, Eric P. Krenning and Theo J. Visser. Endocrine Reviews. August 2001; 22(4):451–476
- ^ Dietrich, J. W., K. Brisseau und B. O. Boehm (2008). “Resorption, Transport und Bioverfügbarkeit von Schilddrüsenhormonen” [Absorption, transport and bio-availability of iodothyronines]. Deutsche Medizinische Wochenschrift 133 (31/21): 1644-8. DOI 10.1055/s-0028-1082780
- ^ Satoru Suzuki, Nobuyoshi Suzuki, Jun-ichirou Mori, Aki Oshima, Shinichi Usami and Kiyoshi Hashizume. μ-Crystallin as an Intracellular 3,5,3′-Triiodothyronine Holder in Vivo. MMolecular Endocrinology April 1, 2007 vol. 21 no. 4 885-894. PMID 17264173
- ^ Military Obstetrics & Gynecology > Thyroid Function Tests In turn citing: Operational Medicine 2001, Health Care in Military Settings, NAVMED P-5139, May 1, 2001, Bureau of Medicine and Surgery, Department of the Navy, 2300 E Street NW, Washington, D.C., 20372-5300
- ^ http://www.ncbi.nlm.nih.gov/pubmed/2884552
- ^ “Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials.” Grozinsky-Glasberg S; Fraser A; Nahshoni E; Weizman A; Leibovici L. J Clin Endocrinol Metab. 2006 Jul;91(7):2592-
- ^ Robert Lloyd Segal, MD Endocrinologist
- ^ a b c “preferred thyroid hormone –Levothyroxine Sodium (Synthroid, Levoxyl, Levothroid, Unithroid)”, Retrieved on 2009-3-27
- ^ a b c d “Hypothyroidism Causes, Symptoms, Diagnosis, Treatment Information Produced by Medical Doctors”, Retrieved on 2009-3-27
- ^ Cooper, DS (1989). “Thyroid hormone treatment: new insights into an old therapy.”.JAMA 261 (18): 2694–2695. doi:10.1001/jama.1989.03420180118042.
- ^ Clyde, PW; Harari AE, Mohamed Shakir KM. (2004). “Synthetic Thyroxine vs Desiccated Thyroid -Reply (citing Cooper, DS, above)”. JAMA 291 (12): 1445.doi:10.1001/jama.291.12.1445-b.
- ^ Thyroid hormone replacement therapy
- ^ a b “Consequences of Not Taking Thyroid Medications – Implications of Failing to Take Prescription Thyroid Drugs”, Retrieved on 2009-3-27
- ^ “Armour Thyroid”, Retrieved on 4-1-2009
- ^ “Nature-Throid”, Retrieved on 4-1-2009
- ^ “Armour Thyroid Shortages Worsening: What Can Thyroid Patients Do?”, Retrieved on 2009-3-27
- ^ Liothyronine
- ^ “Thyroid Information”, Retrieved on 2009-3-27
- ^ “Desiccated thyroid in a nutritional supplement | Journal of Family Practice | Find Articles at BNET”, Retrieved on 2009-3-27
- ^ “Nature-Throid”, Retrieved on 4-1-2009
- ^ Kirkegaard C, Faber J (1998). “The role of thyroid hormones in depression”. Eur J Endocrinol 138 (1): 1–9. doi:10.1530/eje.0.1380001. PMID 9461307.
- ^ Dratman M, Gordon J (1996). “Thyroid hormones as neurotransmitters”. Thyroid 6 (6): 639–47. doi:10.1089/thy.1996.6.639. PMID 9001201.
- ^ Berbel P, Navarro D, Ausó E, Varea E, Rodríguez AE, Ballesta JJ, Salinas M, Flores E, Faura CC, de Escobar GM. (2010). Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity. Cereb Cortex. 20(6):1462-75. PMID 19812240.
- ^ Spiegel C, Bestetti GE, Rossi GL, Blum JW (September 1993). “Normal circulating triiodothyronine concentrations are maintained despite severe hypothyroidism in growing pigs fed rapeseed presscake meal”. J. Nutr. 123 (9): 1554–61. PMID 8360780.
- ^ a b “Thyroid Disease: A Natural/Herbal Perspective — Interview with Shasta Tierra-Tayam, L.Ac”, Retrieved on 2009-3-27
- ^ “Low Iodine Diet Food List – National Institutes of Health”
- ^ “Health Consequences of Iodine Deficiency”
- ^ “Hypothyroidism Causes, Symptoms, Diagnosis, Treatment Information Produced by Medical Doctors”, Retrieved on 2009-3-27