Endocrinology 5 - Thyroid Hormones Thyroid hormones are amine-based hormones but acts like a steroid hormone Cell permeants - when released from the thyroid they diffuse out with no purpose No receptor or channel needed to move around this hormone TRH - thyrotropin-releasing hormone Releasing hormone (from the hypothalamus and binds to tiotrops on the anterior pituitary and causes it to release TSH) TSH - thyroid stimulating hormone Use this to diagnose diseases MIT - monoiodotyrosine DIT - diiodotyrosine The two above are inactive, but are the building blocks for the two hormones that are biologically active, which are the ones below T3 - triiodothyronine T4 - thyroxine (tetraiodothyronine) TG - Tg, thyroglobulin TBG - thyroid binding globulin Bind thyroid hormones as they circulate through the blood Thyroglobulin is the backbone for the molecules which sit as they are passed through the cells that make thyroid hormones D1-D3 - deiodinases Enzymes that will deiodinate thyroid hormones Can make t4 to t3 T3 to t2 Essentially inactivating T3 and will activate T4 TR - THR, thyroid receptor RXR - retinoid X receptor (coregulator) Tyrosine HO H H =0 T -C-C-C 1 H NH2 `OH Thyroxine (T4) I I I H H C-C ~~ HO 0 I I H NH2 1 OH (2 tyrosine + 4 1 ) Tyrosine HO H H TT O=0 `OH H NH2 Triiodothyronine (T3) 1 I HO I H H 1 0=0 0 C-C-C / I H NH2 OH (2 tyrosine + 3 1 ) Thyroid Stimulating Hormone (TSH) - TSH binds to the (TSHR) - Released by the anterior pituitary - regulates the production of the molecules associated with t3 and t4 production
- Mutations in the TSHR may lead to several thyroid diseases (hyperthyroidism) - TSHR is divided into two subunits (a and B) with each unit linked via disulphide bonds - It's also a GPCR o And involved in Gs/Gq Hypothalamus Stimulus e.g. cold exposure VTRH Anterior Pituitary Thyroid Gland H ITS bled in your web browser. Press play to start. \ T3/T4 16 T4 -> T3 Thyroid Hormone Synthesis
Capillary Interstitial fluid Follicle cell 1 lodide is cotransported with Na+ Na+ 2 Diffusion Pendrin RBC Na+ - TG TG is synthesized in follicle Na+ cell and secreted to colloid Lysosomes Free amino acids re-used for TG synthesis Na* Lysosomal enzymes release T3 6 and T4 from TG 7 T T4 Secretion QT4 S?-?T3 Endocytosis of thyroglobulin containing T3 and T4 molecules Orange part - follicle cell Red matter - colloid (lumen of the follicle) Lumen of follicle (colloid) 3 lodide is transported to colloid, oxidized, and attached to rings of tyrosines in thyroglobulin (TG) S OH (DIT) 1 - OH (MIT) TG 4 The iodinated ring of one MIT or DIT is added to a DIT at another spot OH (T3) -OH (T4) Iodide is co transported into the follicle and diffuses across the cell into the colloid and oxidised and attached to the thyroisines rings in the thyroglobulin Iodinated ring of the