Thyroid hormone: Difference between revisions
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===== Up-Regulatory processes ===== | ===== Up-Regulatory processes ===== | ||
1 5'-Deiodinase produces T<sub>3 </sub>from T<sub>4</sub> in the plasma. | 1 5'-Deiodinase produces T<sub>3 </sub>from T<sub>4</sub> in the plasma. | ||
2 5'-Deiodinase produces T<sub>3</sub> from T<sub>4</sub> in the brain and pituitary providing for the CNS. | 2 5'-Deiodinase produces T<sub>3</sub> from T<sub>4</sub> in the brain and pituitary providing for the CNS. | ||
===== Down-Regulatory processes ===== | ===== Down-Regulatory processes ===== | ||
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3 5'-Deiodinase produces rT<sub>3</sub>, an inactive form of T<sub>3</sub>, thus reducing the effects of active thyroid hormone. | 3 5'-Deiodinase produces rT<sub>3</sub>, an inactive form of T<sub>3</sub>, thus reducing the effects of active thyroid hormone. | ||
=== Regulation of Thyroid Hormone release === | === Regulation of Thyroid Hormone release === | ||
The production and secretion of thyroid hormones is controlled by the [[Hypothalamo-hypophyseal axis]]. | The production and secretion of thyroid hormones is controlled by the [[Hypothalamo-hypophyseal axis]]. | ||
The [[Hypothalamus]] secretes [[Thyrotrophin-Releasing Hormone]] into the [[ | The [[Hypothalamus]] secretes [[Thyrotrophin-Releasing Hormone]] into the [[Medial eminence|medial eminence]] which drains into the [[Hypophyseal portal system|hypophyseal portal system]]. This carries the TRH to the adenohypophysis, or [[Anterior_pituitary_gland|anterior pituitary gland ]]where it acts on [[Thyrotroph|thyrotrophs]] which secrete [[Thyroid stimulating hormone|Thyroid-Stimulating Hormone]]. | ||
===== Effects of Thyroid-Stimulating Hormone ===== | ===== Effects of Thyroid-Stimulating Hormone ===== | ||
*Upregulation of thyroglobulin gene transcription | *Upregulation of thyroglobulin gene transcription | ||
*Upregulation of thyroperoxidase gene transcription | *Upregulation of thyroperoxidase gene transcription | ||
*Binds to receptors on Na<sup>+</sup>/I<sup>-</sup> Symporter causing it to open, thus increasing uptake of iodine into follicular cells | *Binds to receptors on Na<sup>+</sup>/I<sup>-</sup> Symporter causing it to open, thus increasing uptake of iodine into follicular cells | ||
*Increases rate of pinocytosis of colloid | *Increases rate of pinocytosis of colloid | ||
*Increases lysosomal activity to degrade incoming colloid and release thyroid hormones | *Increases lysosomal activity to degrade incoming colloid and release thyroid hormones | ||
*Increases thyroid cell size | *Increases thyroid cell size<br> | ||
=== Effects of Thyroid Hormone === | |||
*Increased protein synthesis | |||
*Increased cellular metabolism, particularly of fats and carbohydrates | |||
*Thermatogenesis | |||
*Increased cardiac output through increased gene transcription of Ca<sup>2+</sup>-ATPase, thus causing increased muscle contraction <ref>Bielecka-Dabrowa, A., Mikhailidis, D.P., Rysz, J., Banach, M. (2009). "The mechanisms of atrial fibrillation in hyperthyroidism.", Thyroid Research 2:4</ref> | |||
*Increased oxygenation of blood due to a higher rate of breathing | |||
*Works synergistically with growth hormone to encourage normal growth in early development | |||
=== Hyperthyroidism === | |||
References | References | ||
<references /> | <references /> | ||
Revision as of 01:03, 10 January 2011
'Thyroid Hormone' is an umbrella term referring to Triiodothyronine, T3, and Thyroxine, T4, two Tyrosine-based hormones produced by the Thyroid gland. Their synthesis involves the iodination of two precursors, monoiodothyronine, T1, and Diiodothyronine, T2. Although thyroxine is produced in larger quantities, it must be noted that triiodothyronine is three to eight times more active. Thus, thyroxine is metabolised into triiodothyronine for active use. The thyroid hormones are involved in growth, working synergistically with growth hormone, in cellular metabolism and in bodily thermogenisis.
The level of thyroid hormones carried in the blood plasma must be regulated; over-active thyroid tissue leads to an increase in circulating thyroid hormones, termed hyperthyroidism, the symptoms of which include goitre. The converse, a deficiency of thyroid hormones, or hypothyroidism can have serious acute effects as well as chronic effects, the latter most serious when presented congenitally.
Synthesis
Thyroxine and Triiodothyronine are based on the amino acid tyrosine and which has been iodinated to varying degrees.
Thyroid tissue is composed of distinct functional units called Follicles. These consist of a central Colloid-containing Lumen surrounded by a thin epithelium of follicular cells [1]. The follicular cells produce a glycoprotein, Thyroglobulin, which is rich in tyrosine residues. This is exocytosed into the colloid where it is stored. Tyrosine residues of thyroglobulin are iodinated to produce monoiodothyronine and diiodothyronine, the precursors to the thyroid hormones, catalysed by the enzyme Thyroperoxidase. [2] The iodine is provided via the Na+/-I-Symporter which actively transports Sodium and Iodide ions into the follicular cells from the blood using free energy released from transporting Na+ down its concentration gradient. [3] Monoiodothyronine and diiodothyronine under go a coupling reaction independant of thyroperoxidase in which the active thyroid hormones, thyroxine and triiodothyronine are yielded.
A coupling of monoiodothyronine and diiodothyronine yields triiodothyronine.
A coupling of two diiodothyronine molecules yields thyroxine (tetraiodothyronine).
Upon stimulation from Thyroid-Stimulating Hormone the colloid is pinocytosed into the follicular cell where the thyroglobulin is degraded within the endocytotic vesicles to release the thyroid hormones.
T3 and T4 enter the bloodstream and is bound to carrier proteins. Only approximately 0.4% T3 and 0.04% of T4 is circulated in free form. 70% of thyroid hormones are bound with high affinity to Thyroxine-Binding Globulin. 10% of T4 is bound to Thyroxine-Binding Prealbumin which has a tenfold greater affinity for T4 than for T3. Around 15% of thyroid hormones are bound with low affinity to albumin which allows rapid dissociation in the tissues.
Metabolism of T4
Around 100nM of T4 are secreted every day, whereas only 5nM of the more active T3 is secreted. T4 is deiodinated to produce a greater concentration of T3 in ways that both up-regulates and down-regulates the level of thyroid hormone in the blood.
Up-Regulatory processes
1 5'-Deiodinase produces T3 from T4 in the plasma.
2 5'-Deiodinase produces T3 from T4 in the brain and pituitary providing for the CNS.
Down-Regulatory processes
3 5'-Deiodinase produces rT3, an inactive form of T3, thus reducing the effects of active thyroid hormone.
Regulation of Thyroid Hormone release
The production and secretion of thyroid hormones is controlled by the Hypothalamo-hypophyseal axis.
The Hypothalamus secretes Thyrotrophin-Releasing Hormone into the medial eminence which drains into the hypophyseal portal system. This carries the TRH to the adenohypophysis, or anterior pituitary gland where it acts on thyrotrophs which secrete Thyroid-Stimulating Hormone.
Effects of Thyroid-Stimulating Hormone
- Upregulation of thyroglobulin gene transcription
- Upregulation of thyroperoxidase gene transcription
- Binds to receptors on Na+/I- Symporter causing it to open, thus increasing uptake of iodine into follicular cells
- Increases rate of pinocytosis of colloid
- Increases lysosomal activity to degrade incoming colloid and release thyroid hormones
- Increases thyroid cell size
Effects of Thyroid Hormone
- Increased protein synthesis
- Increased cellular metabolism, particularly of fats and carbohydrates
- Thermatogenesis
- Increased cardiac output through increased gene transcription of Ca2+-ATPase, thus causing increased muscle contraction [4]
- Increased oxygenation of blood due to a higher rate of breathing
- Works synergistically with growth hormone to encourage normal growth in early development
Hyperthyroidism
References
- ↑ Hadley, M. E (2000) Endocrinology 5th Edition, Upper Saddle River, Prentice Hall
- ↑ Ruf, J., Carayon, P. (2006). "Structural and functional aspects of thyroid peroxidase." Archives of Biochemistry and Biophysics 445: 2; 269-277
- ↑ Li, C.C., Ho, T.Y., Kao, C.H., Wu, S.L., Liang, J.A., Hsaing, C.Y. (2010). "Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity.", Journal of Biomedical Science, 17: 89
- ↑ Bielecka-Dabrowa, A., Mikhailidis, D.P., Rysz, J., Banach, M. (2009). "The mechanisms of atrial fibrillation in hyperthyroidism.", Thyroid Research 2:4