T4 & T3 – Iodine containing derivatives of thyronine

T4-thyroxine ( 3,5,3ˈ,5ˈ -tetraiodothyronine)

T3-triiodothyronine (3,5,3ˈ triiodothyronine)

SYNTHESIS

Thyroglobulin molecule-glycoprotein synthesized by thyroid cells

MW-660 KDa.

1. Iodine uptake

2. Oxidation and Iodination 3.Coupling

4.Storage and release

5. Peripheral conversion of T4 to T3

Plasma protein bound- 0.03-0.08 % T4

0.2-0.5% T3

Binding occurs to 3 plasma proteins1)Thyroxine binding globulin (TGB)2)Thyroxine binding prealbumin (transthyretin)3)Albumin

Normal concentration of PBI- 4-10µg/dl0.1-0.2 µg/dl – T3, rest is T4.

Relation between T4 and T3

Thyroid secrets more T4 than T3

T4 is major circulating hormone

T3 is 5 times more potent than T4 and acts faster.

T3 is more avidly bound to the nuclear receptor than T4.

About 1/3 of T4 is converted to T3 in peripheral tissues.

On the basis of this ,it is believed that T3 is the active hormone & T4 is only the transport form.

THYROID STIMULATING HORMONE

It is 210 amino acid, two chain glycoproteinMW 30000

FUNCTIONS

Stimulates thyroid to synthesize and secrete thyroxin (T4) & Triiodothyronin (T3)

-Induces hyperplasia & hypertrophy of thyroid follicles

-Promotes trapping of iodide by thyroid

-Promotes organification of trapped iodine & its incorporation into T3 & T4 By increasing Peroxidase activity

-Enhances endocytotic uptake of thyroid colloid by the follicular cells

-Proteolysis of thyroglobulin to release more T3 & T4.

Nuclear thyroid hormone receptor

ACTIONS

1)Growth and development2)Intermediary metabolism3)Calorigenesis4)CVS5)Nervous system6)Skeletal muscle7)GIT8) Kidney

1.Cretinism

2.Adult hypothyroidism

3.Myxoedema coma

4.Nontoxic goiter

5.Thyroid nodule

6. Papillary carcinoma of thyroid

Thyrotoxicosis-main causes Graves Disease

Toxic nodular goiter

Classification

1.Inhibit hormone synthesis(Antithyroid drugs)

2.Inhibit iodide trapping (ionic inhibitors)

3.Inhibit hormone release

4. Destroy thyroid tissue

PropylthiouracilMethimazoleCarbemazole

IodineIodides of Na & KOrganic iodide

Thiocyanates(-SCN)Perchlorates (-ClO4)Nitrates (-NO3)

Radioactive iodine (131I,125I,123I)

Inhibits thyroid hormone release- Lithium

Inhibit peripheral conversion of T4 to T3- Amiodarone

Inhibit thyroglobulin iodination and coupling reaction- Sulphonamides Paraaminosalicylic acid

Induce metabolic degradation of T4/T3- Phenobarbitone Phenytoin Carbamazepine Rifampin