Mechanism of Action of Thyroid Hormones
Hey friends, in this video we will see mechanism of action of thyroid hormones. So let’s start. Okay so as usual we have the cell. It is its nucleus and this is a gene. And this is thyroid hormone response element on promoter region of this gene. And this is thyroid hormone receptor. The thyroid hormone receptors are similar to steroid hormone receptors. It has a ligand binding domain at carboxy terminal, DNA binding domain with two zinc fingers in middle part and an transactivation domain at amino terminal. Now, the thyroid hormone receptor is a transcription factor. Transcription factor is basically a protein that regulates expression of genes. It has two types: alpha and beta. Different tissues expresse different types. Now without thyroid hormone, the thyroid hormone receptor forms a homodimer with another such thyroid hormone receptor. They are bound with a co-repressor molecule which keeps gene expression suppressed. Now let’s see what happens when thyroid hormone comes. okay, so here we have thyroid hormones. They enter into the cell passively or actively by some nonspecific transporters. as we have seen in video of transport and peripheral conversion of thyroid hormones, T4 is converted into T3 by deiodinase enzyme. Now this T3 enters into the nucleus and binds at the ligand binding domain Thyroid hormone receptor has ten times more affinity for T3 than T4. That is one of the reason why T3 is responsible for most of the thyroid hormone activity. Now this binding separates thyroid hormone receptors and causes binding with retinoid X receptor. Thus forming a heterodimer It also causes conformational changes in the receptor so now co-repressor is released and co-activator binds here. This complex now induces gene transcription. Thus forming mRNA. The mRNA is transported into the cytoplasm and translated by ribosome to produce the respective protein. Likewise, different proteins are produced in different tissues. These proteins include functional proteins which contribute into the metabolism and various structural proteins which contribute into the growth. Now as the effect of thyroid hormones involves synthesis of proteins it takes some time for its effects to manifest. Apart from this main mechanism of action, it is believed that the thyroid hormone produces immediate effects by acting on cell membrane, mitochondria etc. So this is the mechanism of action of thyroid hormones. Now let us have a quick summary. So this is the thyroid hormone receptor This is the ligand binding domain, this is DNA binding domain with zinc fingers and this is transactivation domain. Without thyroid hormone it forms homodimer with another such thyroid hormone receptor and bound with co-repressor which binds with thyroid hormone response element and keeps the gene expression suppressed. The thyroid hormones entere into the cell passively or by active transport by some nonspecific transporters. T4 is converted into T3 by deiodinase enzymes. T3 binds with the thyroid hormone receptor which causes disruption of homodimer and formation of heterodimer with retinoid X receptor. The co-repressor molecule is released and coactivator molecule binds here which induces the transcription of gene forming mRNA. The mRNA is transported into the cytoplasm where protein is synthesized from it. These proteins are various functional and structural proteins which contributes into the metabolism and growth. Due to involvement of protein synthesis in this process it takes some time. Apart from this delayed effects, the thyroid hormones are also believed to produce immediate effects by acting on cell membranes and certain organelles like mitochondria. So that’s it for this video. If you found this video helpful please share it with your colleagues and don’t forget to subscribe because lots more to come. Thank you.