Slayt 1

THYROID HORMONESProf.Dr.Arzu SEVENThyroid hormone biosynthesis involves thyroglobulin and iodide metabolism

THYROD HORMONES1- Concentration of iodide In the follicular epithelial cells, against a strong electrochemical gradientEnergy-dependent process, linked to ATPase dependent Na+ - K+ pumpThyroidal I- transporter (controlled by TSH)odide in thyroid/iodide in serum ratio reflects the activity of this transporter (25/1)odide transporter is inhibited by perchlorate and thiocyanate

2- Oxidation of I- by thyroid peroxidase (TPO) in the peroxisome to iodineAs an oxidizing agent, TPO requires H2O2, produced by NADPH-dependent enzyme (like cytocrome c reductase). Antithyroid drugs-thiourea-inhibit I- oxidation 3- Iodination of tyrosine (organification) oxidized ioide reacts with tyrosyl residues in thyroglobulin (involves TPO) to form MIT or DITThyroglobulin:ProhormonePrecursor and storage form of T4 and T3Large, iodinated and glycosylated proteinComposed of 2 subunistContains 115 tyrosine residues

Thyroglobulin is synthesized in the basal portion of the cell. It is stored in the extracellular colloid4- Coupling of iodotyrosyls

(catalysed by TPO, inhibited by antithyroid drugs ) 5-Thyroglobulin (Tgb) hydrolysis stimulated by TSH (or cAMP) inhibited by I- ncrease in microvilli on the apical membrane phagocytosis + pinocytosis, bring Tgb back into the follicular cellPhagosomes + lysosomes phagolysosomes in which acid proteases and peptidases hydrolyse Tgb into amino acids and iodothyroninesT3 and T4 are discharged from the basal portion of cell by facilated process into blood MIT DIT~ 70% of iodide in Tgb exists in inactive precursors (MIT, DIT) ,~ 30% in T4 and T3

TyrosinedeiododinaseI-When iodine supplies are sufficient T4/T3: 7/1In iodine deficiency, T4/T3 , DIT/MIT Daily iodide requirement: 150-200 g

Transport of thyroid hormonesThyroxine binding globulin (TGB) 70% Albumin 25%Thyroxine binding prealbumin (TBPA) 5%TBG, a glycoprotein, binds nearly all T4 and T3 noncovalently TBG is produced in liverIts synthesis is, increased by estrogens ,decreased by androgens or glucocorticoid therapy and in liver diseasePhenytoin and salicylates compete with T3 and T4 to bind to TBGThe small, unbound (free) fraction is responsible for biological activityFree T4 and T3 is a measure of thyroid hormone status, represents