Thyroid gland the sheet contains mostly everything but please refer to (slides 4) for further assistance. NOTE: thyroid hormones are amines that exhibit both peptides & steroidal hormones characteristics. NOTE: thyroid hormones play a permissive effect with GH.. Causing growth (function) **1- thyroid hormones synthesis, release, transport & metabolism.** refer to figure 32-3 & 48-3 iodide uptake through Na/I carrier(sympoter) iodide trapping(accumulation) in the cell activated iodide transported into the colloid through pendrin carrier facilitated by TSH ((( at the same time))) thyroglobulin glycoprotein precursor is synthesized by the follicular thyroid cells in the RER & modified in the Golgi apparatus, then secreted into the colloid (thyroglobulin is a principle component of the colloid) secondly(iodination) thyroglobulin- composed of a minimum number of 70 tyrosine amino acidshould undergo iodination : binding of tyrosine on thyroglobuline with iodide ( a process done through 1- oxidation by the help of peroxidase enzyme; an enzyme that bring tyrosine found on thyroglobulin in contact with iodide found free in the colloid- then by 2- organification monoiodotyrosine & di-iodotyrosine formed) Oxidation(peroxidase) ---- iodide & thyroglobulin free radicals(intermediates) ---- Organification(MIT & DIT formation) Note: tyrosine doesn t bind iodide freely in the colloid but should be bound to thyroglobulin in order for peroxidase to function (iodination and coupling don t occur unless the tyrosines are bound to thyroglobulin) thirdly(coupling) coupling of 2 (MIT, DIT) together to form iodothyronine (T4,T3) stored by being bound to thyroglobulin and released by TSH stimulation. (MIT-DIT)or(DIT-DIT) = coupling.. Note: T3 is the active form of the thyroid hormone, however T4 makes up the majority of thyroid hormones. * All T4 (100%) is produced from thyroid * T3 : 25% from thyroid and 75% from T4 * rt3 : 5% from thyroid and 95% from T4 - T3 and rt3 are mainly produced from the metabolism of T4 - This conversion (metabolism) happen either inside the thyroid or in the peripheral tissues (mainly in the peripheral tissues). 2- Half-life : T4 is almost inactive "7 days" T3 ----- "1 day" rt3 ---- "0.8 day" Daily production (in micrograms) : ((90)) T4, ((35)) T3 and ((35)) rt3
fourthly(release) this process is done by the binding process of TSH to thyroid receptors stimulating the release of the hormone by pinocytosis from the luminal colloid forming colloid droplet then by lysosomal proteases the colloid vesicle is digested within the follicular cells into ( MIT & DIT from thyroglobulin to be recycled + T4,T3 relased from the cells into the circulation). NOTE: further metabolism of the pro- hormone thyroxin(t4) is mediated by deiodinases 1,2,3 which cleave iodine from T4 to produce the activet3 & inactive rt3 or may produce di-iodothyronine(functionless) NOTE: there is a difference between thyroid hormone storage & iodide storage duration ex: 1 month storage duration of the hormone means 2 months storage of iodide * Refer to (figure 32.4) for the metabolism of thyroxin (T4): Thyroid gland mainly produces T4. T4 is activated (by D1) to produce T3 of course under the effect of enzymes. Or it is inactivated (by D3) to produce rt3. The enzymes are (D)eiodinases type 1, 2, 3. Then rt3 produce diiodothyronine (by D1) (notice that it's diiodothyronine not diiodotyrosine because it comes from hormones) T3 is inactivated (by D3) to produce diiodothyronine NOW when the active hormone is needed T4 produces T3 when there is a lot of T4 and no need for the hormone it produces rt3. When T3 and rt3 are saturated, T4 produces Tetraiodoacetic acid (tetrac) we refer to it as decarboxylated and deaminated form of T4 (which is the third choice). Conclusion(important) thyroid gland produce (iodothyronine T3,4 MIT DIT) follicular cells produce. thyroid hormones (colloid droplet degradation) while iodination & coupling take place in the colloid before pinocytosis into the follicular cells take place. parafollicular cells produce.. calcitonin reducing serum [Ca++] which oppose the action of parathyroid hormone. NOTE: iodination mechanism : iodide bind to tyrosine in 2 places (thyroglobuline-tyrosine-i thyroglobulin-tyrosine-tyrosine- I ) OR NOTE: 4-8 tyrosine a.a found on thyroglobulin undergo iodination not the whole 70 a.a!! NOTE: keep in mind that GH & IGF-1 are the major determinants of growth in normal postuterine life. However, other hormones are completely serious for growth.
NOTE: remember that thyroid gland start functioning after week 10 of gestation as it s essential for CNS & MSS development because the thyroid hormones produced by the mother 1- can t be utilized by the fetus or 2- even stimulate the fetus thyroid gland. ** 2- Thyroid hormones after the release into the circulation ** - thyroid hormones are very dangerous, should be kept in the range of their consentration so they travel bound to different plasma proteins mainly TBG(thyronine binding globulin) - why bound to plasma proteins?! 1- to be prevented from filtration as they are small a.a 2- to prolong their t1/2 T4 binds with 3 types of TBG(thyroxin-B-G) : -T3 binds with 3 types of TBG(thyroxin-B-G) : 75% of T3 is bound to TBG(thyronine-B-G) 75% of T4 is bound to TBG(thyronine-B-G) 10 % of T4 is bound to Albumin very low affinity 15% of T4 is bound to TBPA 99.98% of T4 is bound to plasma proteins TBG(thyroxin-B-G) 25% of T3 is bound to Albumin very low affinity T3 doesn't bind TBPA 99.5% of T3 is bound to plasma proteins TBPA= thyroxin binding pre-albumin ** 3- Thyroid hormones after reaching target cells ** - thyroid hormones(t4,3) enter the cells by diffusion or by carrier-mediated transport to bind to their receptors found in the nucleus. - the doc mentioned information related to the fact that thyroid hormones bind to other receptors - away from our topic- in which these receptors are bound to retinoid-x-factor to produce different function. Also, vitamin D does so for further knowledge in relation, go back to the reference books available. **4- Thyroid hormones inside cells intracellular & whole body effects ** - thyroid hormones are small molecules, enter the cell membrane and the nuclear membrane, binds the receptors affecting DNA and producing mrna.
- 1- this will lead to increase Na/K pump ATPase activation, increase respiratory enzymes, increase other enzymes & proteins production.. increase proteins for growth and maturation. (intracellular) This requires increased O2 consumption which results in increased metabolic rate. - 2- To increase O2 consumption, we need increased cardiac output as well as increased ventilation. and also Substrates by increased food intake and mobilization of endogenous carbohydrate, protein and fat. as a result to Increased metabolic rate all this will take place : increase thermogenesis (Temperature increase) and also increase CO2 and urea( because there is breakdown of proteins ) while decrease muscle mass and adipose tissue. - This is simply the function of thyroid hormones * Refer to table 9-8 : Regulation of thyroid hormone secretion -Stimulatory Facrors : 1.TSH --> T3,T4 then feedback inhibition Or stimulation when there is low concentration of T3 and T4.Major factor 2.Thyroid-stimulating immunoglobulins : produced abnormally in case of graves disease. TSI 3. Increased TBG levels - Inhibitory Factors : 1. I- deficiency 2. Deiodinase deficiency 3. Excessive I- intake 4. Perchlorate; thiocyanate 5. propylthiouracyl 6. Decreased TBG levels NOTES(important) * Multiple hormones, including growth hormone (GH), insulin like growth factors (IGF-I and II) "they function synergistically" insulin, thyroid hormones, glucocorticoids (cortisol), NOTE again: GH & IGF-I have been implicated as the major determines of growth in normal postuterine life. * Thyroid hormones are essential in normal amounts for growth ; excess does not produce overgrowth as with GH, but causes increase catabolism of proteins & other nutrients ( people with hyperthyroidism are weak because of catabolism of proteins & other nutrients.. carbohydrate,fat).
* Thyroxine at normal concentrations has permissive effect on the action of GH on protein synthesis in its absence amino acids uptake & protein synthesis are not much stimulated (similar to the cooperation with adrenaline which requires the action of thyroxine first on adipose tissue so as to release or cause the release of free fatty acids. The same, thyroxine functions with growth hormone as permissive). * Reduce thyroid activity in childhood produces dwarfs who are mentally retarded, whereas reduced GH in childhood produces dwarfs with normal intelligence. * Refer to Table 9-9 for a comparison between hyperthyroidism & hypothyroidism *refer to thyroid under activity * focus on the notes in bold & underlined Hypothyroidism (found in slides too) The dwarf of the thyroid gland hypofunction in infants is called "cretin" to differentiate it from the deficiency of GH. In the child gross dwarfing, the condition is called cretinism in which the patient encounters failure of skeletal, sexual and mental growth and development. All "milestones" of babyhood are delayed. In the adult, when there is hypofunction the condition is called myxoedema --- slowing up of all bodily processes: - Tissue oxidation are depressed - The basal metabolic rate falls - Less heat is produced - Body temperature falls.. Energy units are stored with water (person feels very cold). - Skin- thick, leathery, puffy, yellow (due to circulating carotene). - Blood cholestrol increases.- Appetite is reduced; weight is gained or stopped. - Gut movements sluggish ---constipation - Heart & respiratory rates and blood pressure reduced. - Thought processes slow down (actually they don't think, they look like dull). - Hair-brittle, sparse,dry. - Slow, husky voice. Bone marrow suppresed -- anaemia. **Hypofunction also produces sterility, so these individuals with (myxoedema) are infertile** Hyperthyroidism - Symptoms : Increased basal metabolic rate (BMR), weight loss because there is destruction (catabolism) of proteins. -Usually two diseases can be noticed in hyperthyroidism : - Causes : 1. Increased thyroid-stimulating immunoglobulins TSI 2. Thyroid neoplasm (cancer) 3. Excess TSH secretion
1. Exopthalmos : protrusion of the eye balls. 2. Goiter : the enlargement of the thyroid gland. ** exophthalmos & goiter** a story to be told so have fun ;) *Exephthalmos (protrusion of eyeballs) may be due to an action of an antibody (which is thyroid stimulating immunoglobulin) against a protein of the extraocular muscles and the connective tissue behind the eye, which causes these tissues to swell It is not due to an excess of thyroid hormones. Exophthalmos: Most but not all persons with hyperthyroidism develop some degree of protrusion of the eyeballs.a major degree of exophthalmos occurs in about one third of hyperthyroid patients. In those people the condition in which the thyroid stimulating immunoglobulin produces this problem. Not all the exophthalmos are caused by TSI, some are caused by it and others are caused by other reasons which we don't know (might be cataract). Exophthalmos is found in most of the hyperthyroidism. TSI may affect the muscles of the eye, it makes the muscles stick so these individuals can't close their eyelids so they will be exposed to blindness as the ocular muscles aren't flexible and can't close the eye. This occur just in these with increased TSI the others may not be exposed to blindness. * u should refer to the table 15-5 * Goiter (enlargement of the thyroid gland) : you can see that the goiter is of 2 types: when there is decrease in T3, T4 this is called "simple benign nontoxic goiter" but when there is increase in T3, T4 this is "malignant toxic goiter". In all of them there is enlargement of the thyroid but by testing we can differentiate between them. simple game to save that(not scientific): if TSH levels are low you won t get goiter except in case of graves disease as TSI would replace TSH action just as if u have high TSH else : tumor, hypothalamic or ANT pituitary failure.. no goiter. Done by: Jamil Ahmad Dedicated to: Ameer Murad, Shaima Shaheen, My friends.