Sandbox Reserved 1779: Difference between revisions
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== Introduction == | == Introduction == | ||
[[Image:surface TSHR.png|400 px|right|thumb|Figure 1. TSHR with TSH bound. The extracellular and transmembrane domains of the GPCR are shown in green, the hinge region in cyan, and thyrotropin bound in magenta. PDB:[https://www.rcsb.org/structure/7UTZ 7UTZ]]] | [[Image:surface TSHR.png|400 px|right|thumb|Figure 1. TSHR with TSH bound. The extracellular and transmembrane domains of the GPCR are shown in green, the hinge region in cyan, and thyrotropin bound in magenta. PDB:[https://www.rcsb.org/structure/7UTZ 7UTZ]]] | ||
[https://en.wikipedia.org/wiki/Thyroid_hormones Thyroid hormones] exercise essential functions related to activity of thyroid cells as well as metabolic processes and oxygen consumption<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. Misregulation of thyroid hormone levels is the cause of many disorders related to [https://www.endocrineweb.com/conditions/thyroid/hyperthyroidism-vs-hypothyroidism hypo- or hyperthyroidism]. Thus, understanding the signaling of synthesis and release of these hormones will have applications in treating [https://www.hopkinsmedicine.org/health/conditions-and-diseases/disorders-of-the-thyroid thyroid hormone disorders]<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. The initiation of the synthesis and release of these hormones is caused by the glycoprotein, thyroid stimulating hormone (TSH), which is released by the anterior pituitary gland<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. The release of TSH from the anterior pituitary is regulated by thyroid-releasing hormone (TRH) which is released by the hypothalamus. When stimulated by TRH, the anterior pituitary releases TSH. When stimulated by TSH, the thyroid gland will produce and release the the thyroid hormones T4 and T3. T3 is the "active form" of the hormone, however it accounts for only 20% of the thyroid hormone that is released after stimulus by TSH. The T4 that predominates in release from the thyroid will be converted to T3 in the bloodstream. High levels of T3 and T4 can negatively regulate the release of TSH from the anterior pituitary, constituting a negative feedback loop <ref name="Pirahanchi et al.">Pirahanchi Y, Toro F, Jialal I. Physiology, Thyroid Stimulating Hormone. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499850/</ref>. The thyrotropin receptor <scene name='95/952709/Initial_scene_with_edited_7utz/5'>(TSHR)</scene> is a [https://www.nature.com/scitable/topicpage/gpcr-14047471/ G-protein coupled receptor] on the surface the thyroid gland cells. TSHR is responsible for binding TSH and transduces signal to initiate synthesis and release of thyroid hormones. In addition to TSH, autoantibodies may also bind to TSHR causing inhibition or activation of its desired function. | [https://en.wikipedia.org/wiki/Thyroid_hormones Thyroid hormones] exercise essential functions related to activity of thyroid cells as well as metabolic processes and oxygen consumption<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. Misregulation of thyroid hormone levels is the cause of many disorders related to [https://www.endocrineweb.com/conditions/thyroid/hyperthyroidism-vs-hypothyroidism hypo- or hyperthyroidism]. Thus, understanding the signaling of synthesis and release of these hormones will have applications in treating [https://www.hopkinsmedicine.org/health/conditions-and-diseases/disorders-of-the-thyroid thyroid hormone disorders]<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. The initiation of the synthesis and release of these hormones is caused by the glycoprotein, thyroid stimulating hormone (TSH), which is released by the anterior pituitary gland<ref name="Yen">Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001 Jul;81(3):1097-142. doi: 10.1152/physrev.2001.81.3.1097. PMID: 11427693.</ref>. The release of TSH from the anterior pituitary is regulated by thyroid-releasing hormone (TRH) which is released by the hypothalamus. When stimulated by TRH, the anterior pituitary releases TSH. When stimulated by TSH, the thyroid gland will produce and release the the thyroid hormones T4 and T3. T3 is the "active form" of the hormone, however it accounts for only 20% of the thyroid hormone that is released after stimulus by TSH. The T4 that predominates in release from the thyroid will be converted to T3 in the bloodstream. High levels of T3 and T4 can negatively regulate the release of TSH from the anterior pituitary, constituting a negative feedback loop <ref name="Pirahanchi et al.">Pirahanchi Y, Toro F, Jialal I. Physiology, Thyroid Stimulating Hormone. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499850/</ref>. The thyrotropin receptor <scene name='95/952709/Initial_scene_with_edited_7utz/5'>(TSHR)</scene> is a [https://www.nature.com/scitable/topicpage/gpcr-14047471/ G-protein coupled receptor] on the surface the thyroid gland cells (Figure 1). TSHR is responsible for binding TSH and transduces signal to initiate synthesis and release of thyroid hormones. In addition to TSH, autoantibodies may also bind to TSHR causing inhibition or activation of its desired function.<ref name="Duan et al.">PMID:35940204</ref><ref name="Kohn et al.">Kohn LD, Shimura H, Shimura Y, Hidaka A, Giuliani C, Napolitano G, Ohmori M, Laglia G, Saji M. The thyrotropin receptor. Vitam Horm. 1995;50:287-384. doi: 10.1016/s0083-6729(08)60658-5. PMID: 7709602.</ref> | ||
== Structure == | == Structure == | ||
=== Active and Inactive Form === | === Active and Inactive Form === | ||
