{"id":1895,"date":"2019-04-16T15:28:13","date_gmt":"2019-04-16T15:28:13","guid":{"rendered":"http:\/\/ibshypo.com\/?page_id=1895"},"modified":"2019-04-23T18:50:25","modified_gmt":"2019-04-23T18:50:25","slug":"resistance-to-thyroid-hormone-rth","status":"publish","type":"page","link":"https:\/\/ibshypo.com\/index.php\/resistance-to-thyroid-hormone-rth\/","title":{"rendered":"Resistance to Thyroid Hormone (RTH)"},"content":{"rendered":"\n

This topic describes genetic RTH using simplified diagrams. <\/p>\n\n\n\n

Thyroid Hormone Receptors<\/h3>\n\n\n\n

There are four thyroid receptor types. Two genes each produce two isoforms. The TR\u03b11 and TR\u03b21 receptors are expressed in most tissues in varying proportions.<\/p>\n\n\n\n

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A mutation of the TR\u03b2 gene produces faulty TR\u03b21 and TR\u03b22 receptors that bind in preference to the wild type receptors, this is called a ‘dominant negative’ effect. The pituitary expresses all three receptor types, but it responds mainly to TR\u03b22. Mutated TR\u03b22 receptors blunt the response of the pituitary leading to higher TSH levels and increased thyroid hormone levels. If there is more resistance in the pituitary than in peripheral tissues the patient may be thyrotoxic (PRTH). If the pituitary and peripheral tissues have a similar level of resistance the patient will asymptomatic, albeit with high thyroid hormone levels (GRTH). In this case tissues expressing predominantly TR\u03b21 will tend to be hypothyroid and tissues with TR\u03b11 will tend to be hyperthyroid. <\/p>\n\n\n\n

Receptor Binding<\/h3>\n\n\n\n

Thyroid hormone receptors can bind to the Thyroid Response Element (TRE) on DNA in three ways. Heterodimer binding is most common, here a thyroid hormone receptor and a vitamin A receptor called a ‘retinoid X receptor’ (RXR) bind to the TRE. One study found that the pituitary can bind thyroid hormone in the absence of an RXR<\/a>. We will come back to this later.<\/p>\n\n\n\n

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The Binding Process<\/h3>\n\n\n\n
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The TR and RXR receptors bind to the TRE on DNA in the absence of hormone, usually leading to transcriptional repression via a ‘co-repressor’. When T3 binds to the receptors the co-repressor is released and replaced by a co-activator leading to DNA transcription which produces messenger RNA used to form proteins. This is how most tissues work, they have ‘positive TREs’.<\/p>\n\n\n\n

The hypothalamus and pituitary respond to T3 in the opposite way, transcription is active until T3 supresses transcription. The hypothalamus and pituitary have ‘negative TREs’.
<\/p>\n\n\n\n

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Next we use this information to find the problem<\/a> that causes hypothyroidism with normal thyroid hormone levels and requires treatment with supraphysiological doses of thyroid hormone.<\/p>\n\n\n\n

<\/p>\n\n\n\n

\n","protected":false},"excerpt":{"rendered":"

This topic describes genetic RTH using simplified diagrams. Thyroid Hormone Receptors There are four thyroid receptor types. Two genes each produce two isoforms. The TR\u03b11 and TR\u03b21 receptors are expressed in most tissues in varying proportions. A mutation of the TR\u03b2 gene produces faulty TR\u03b21 and TR\u03b22 receptors that bind in preference to the wild […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/pages\/1895"}],"collection":[{"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/comments?post=1895"}],"version-history":[{"count":43,"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/pages\/1895\/revisions"}],"predecessor-version":[{"id":2550,"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/pages\/1895\/revisions\/2550"}],"wp:attachment":[{"href":"https:\/\/ibshypo.com\/index.php\/wp-json\/wp\/v2\/media?parent=1895"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}