Thyroid hormonesThe steroid hormones are all derived from cholesterol. Moreover, with the exception of vitamin Dthey all contain the same cyclopentanophenanthrene ring and atomic numbering system as cholesterol. The conversion of C 27 cholesterol to the, and carbon steroid hormones designated by the nomenclature C with a subscript number indicating the number of carbon atoms, e. C 19 for androstanes involves the rate-limiting, steroids thyroid hormones cleavage of a 6-carbon residue from cholesterol, producing pregnenolone C 21 plus isocaproaldehyde. Common names of the steroid hormones are widely recognized, but systematic nomenclature is gaining acceptance and familiarity with both steroids thyroid hormones is increasingly important.
Thyroid Hormone Receptors
The thyroid gland makes and releases two hormones: They are tyrosine -based hormones that are primarily responsible for regulation of metabolism. T 3 and T 4 are partially composed of iodine see molecular model. A deficiency of iodine leads to decreased production of T 3 and T 4 , enlarges the thyroid tissue and will cause the disease known as simple goitre. The major form of thyroid hormone in the blood is thyroxine T 4 , which has a longer half-life than T 3.
T 4 is converted to the active T 3 three to four times more potent than T 4 within cells by deiodinases 5'-iodinase. These are further processed by decarboxylation and deiodination to produce iodothyronamine T 1 a and thyronamine T 0 a.
All three isoforms of the deiodinases are selenium -containing enzymes, thus dietary selenium is essential for T 3 production. Edward Calvin Kendall was responsible for the isolation of thyroxine in The thyroid hormones 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 neural 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. Both T 3 and T 4 are used to treat thyroid hormone deficiency hypothyroidism. They are both absorbed well by the gut, so can be given orally. Levothyroxine is the pharmaceutical name of the manufactured version of T 4 , which is metabolised more slowly than T 3 and hence usually only needs once-daily administration.
Levothyroxine Sodium is usually the first course of treatment tried. Some patients feel they do better on desiccated thyroid hormones; however, this is based on anecdotal evidence and clinical trials have not shown any benefit over the biosynthetic forms. Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia , which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock.
Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger in Today most patients are treated with levothyroxine, or a similar synthetic thyroid hormone. Some studies show that the mixed therapy is beneficial to all patients, but the addition of lyothyronine contains additional side effects and the medication should be evaluated on an individual basis.
In fact, if a woman who is hypothyroid is left untreated, her baby is at a higher risk for birth defects. When pregnant, a woman with a low-functioning thyroid will also need to increase her dosage of thyroid hormone. Thyroid hormones T 4 and T 3 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 T 4 in vivo are mediated via T 3 T 4 is converted to T 3 in target tissues. T 3 is 3- to 5- fold more active than T 4. 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 thyroxine-binding globulin TBG , which is cleaved by enzymes to produce active T 4.
The steps in this process are as follows: Thyroglobulin Tg is a kDa , dimeric protein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. The thyroglobulin protein accounts for approximately half of the protein content of the thyroid gland. This introduces atoms of the element iodine , covalently bound, per tyrosine residue.
Thyroxine is believed to be a prohormone and a reservoir for the most active and main thyroid hormone T 3. Thyrotropin-releasing hormone TRH is released from hypothalamus by 6 — 8 weeks, and thyroid-stimulating hormone TSH secretion from fetal pituitary is evident by 12 weeks of gestation , and fetal production of thyroxine T 4 reaches a clinically significant level at 18—20 weeks.
If there is a deficiency of dietary iodine , the thyroid will not be able to make thyroid hormone. The lack of thyroid hormone will lead to decreased negative feedback on the pituitary, leading to increased production of thyroid-stimulating hormone , which causes the thyroid to enlarge the resulting medical condition is called endemic colloid goitre ; see goitre.
This has the effect of increasing the thyroid's ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone. Most of the thyroid hormone circulating in the blood is bound to transport proteins. Only a very small fraction of the circulating hormone is free unbound and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value.
For this reason, measuring total thyroxine in the blood can be misleading. Despite being lipophilic, T 3 and T 4 cross the cell membrane via carrier-mediated transport, which is ATP-dependent. T 1 a and T 0 a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor TAAR1 TAR1, TA1 , a G-protein-coupled receptor located in the cell membrane.
Another critical diagnostic tool is measurement of the amount of thyroid-stimulating hormone TSH that is present. Contrary to common belief, thyroid  hormones cannot traverse cell membranes in a passive manner like other lipophilic substances.
The iodine in o -position makes the phenolic OH-group more acidic, resulting in a negative charge at physiological pH. However, at least 10 different active, energy-dependent and genetically-regulated iodothyronine transporters have been identified in humans. They guarantee that intracellular levels of thyroid hormones are higher than in blood plasma or interstitial fluids.
Little is known about intracellular kinetics of thyroid hormones. The thyroid hormones function via a well-studied set of nuclear receptors , termed the thyroid hormone receptors.
These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements TREs near genes. This receptor-corepressor-DNA complex can block gene transcription. When triiodothyronine T3 binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase , activating transcription of the gene. Thyroxine and iodine stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibian metamorphosis, and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog.
In fact, amphibian frog Xenopus laevis serves as an ideal model system for the study of the mechanisms of apoptosis. Thyroxine and triiodothyronine can be measured as free thyroxine and free triiodothyronine , which are indicators of thyroxine and triiodothyronine activities in the body.
They can also be measured as total thyroxine and total triiodothyronine , which also depend on the thyroxine and triiodothyronine that is bound to thyroxine-binding globulin. A related parameter is the free thyroxine index , which is total thyroxine multiplied by thyroid hormone uptake , which, in turn, is a measure of the unbound thyroxine-binding globulins. 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.
Iodine uptake against a concentration gradient is mediated by a sodium-iodine symporter and is linked to a sodium-potassium ATPase. Perchlorate and thiocyanate are drugs that can compete with iodine at this point. Compounds such as goitrin , carbimazole , methimazole , propylthiouracil can reduce thyroid hormone production by interfering with iodine oxidation. Thyroid hormone treatment in thyroid disease. From Wikipedia, the free encyclopedia. This article needs additional citations for verification.
Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. April Learn how and when to remove this template message. The structural formula left and a space-filling model right of S -triiodothyronine T 3 , also called liothyronine in the pharmaceutical industry. The structural formula left and a space-filling model right of S -thyroxine T 4. This section needs additional citations for verification.
This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Retrieved 2 May American Society for Biochemistry and Molecular Biology. The Journal of Clinical Endocrinology and Metabolism. Angewandte Chemie International Edition. The Journal of the American Medical Association. Hormone Research in Paediatrics. What Can Thyroid Patients Do? Journal of Family Practice. Medical Physiology 2nd ed. Edward; Kester, Monique H. A Cellular And Molecular Approaoch.
Current Concepts and Challenges". Oxford Textbook of Endocrinology and Diabetes 2nd ed. Oxford Textbook of Endocrinology and diabetes 2nd ed. Journal of Clinical Investigation. Journal of Cell Death. Journal of Molecular Endocrinology. European Journal of Endocrinology. Thyroid hormone T 3 T 4 Calcitonin Thyroid axis. Levothyroxine Liothyronine Liotrix Tiratricol Thyroid gland preparations.