18th November 2016 Endocrinology The Thyroid Gland Hormones of thyroid · TRH - Thyrotropin-releasing hormone Released from the hypothalamus · TSH - Thyroid stimulating hormone First thing we measure when we are looking for a problem of the thyroid - TRH binds to receptors in AP to release this. Low TSH suggests a form of inhibitory feedback to reduce the thyroid hormone production (hyperthyroidism). High TSH is hypothyroidism due to low thyroid hormone production. · MIT - Monoiodotyrosine from a thyroid precursor · DIT - Diiodotyrosine from a thyroid precursor · T3 - Triiodothyronine from a thyroid precursor · T4 - Thyroxine (tetraiodothyronine) from a thyroid precursor · TG - Tg, thyroglobulin binds to precursor molecules during the process of iodination · TBG - Thyroid binding globulin it is a circulating protein that binds thyroid hormones D1-D3 - Deiodinases System of enzyme in different tissues of the body, they remove iodide from the hormones; can convert T4 to T3 (inactive thyroid hormones · TR - THR, thyroid receptor they are like steroid hormones and can diffuse across the cell membrane and can bind to a nuclear receptor • RXR - Retinoid X receptor (coregulator) nuclear receptor Thyroid Glands - composed of follicles Thyroid gland is a lobular organ found around the cartilage in the oesophagus. It is made up of follicular cells surrounding the colloid (aquous solution with lots of protein). Thyroid gland Right lobe Isthmus Thyroid cartilage Left lobe Trachea Thyroid hormones synthesised by iodination of tyrosine on thyroglobulin. Follicular cells and colloid have important roles in making TH. Follicular cells Follide
18th November 2016 Endocrinology Thyroid hormone structures Tyrosine HO H H O= C-C-C H NH2 OH Tyrosine HO H H .0 -C-C-C H NH2 `OH Thyroxine (T4) I I I H H HO C-C ~~ 20 0 I I H NH2 `OH (2 tyrosine + 4 1 ) Triiodothyronine (T3) I I I H H T HO 0 -C-C-n=0 - I H NH2 1 OH (2 tyrosine + 3 1 ) Exogenous thyroxine is given to those with hypothyroidism - 7th most prescribed drug Thyroid hormones are involved with lipid homeostasis; those with hypothyroidism have higher blood triglycerol levels; there is a higher increase in cardiovascular attacks. By taking the hormone, it reduces the chance. The number of iodide bonds correlate to the name T3 and T4. Action of TSH on the Thyroid Tropic hormone released from the anterior pituitary gland TSH acts on follicular cells of the thyroid, binding to the follicular cells: - Increases iodide transport into follicular cells - Increases production and iodination of thyroglobulin - Increases endocytosis of colloid from lumen into follicular cells Colloid contains the precursor molecules the MIT and DIT. follicular cells Na+ K+ I Na+ follicle cell colloid droplet endocytosis Aston University thyroglobulin 1 T3 T4 1 ATP thyroglobulin I- thyroglobulin iodination
18th November 2016 Endocrinology Thyroid Hormone Synthesis 1. Iodide is transported in a co-transporter mechanism with sodium into the follicular cell 2. It the diffuses across the