The role of thyroid hormones in the regulation of metabolism.

THYROID GLAND Thyroid gland synthesizes two kinds of hormones: iodine containing hormones and calcitonin.

Hormones of two types: 1. Iodine containing : thyroxin (tetraiodthyronin) and triiodthyronin – derivatives of tyrosine; 2. Calcitonin - peptide 3

Synthesis of iodine containing hormones is regulated by thyrotropic hormone, which in turn is stimulated by thyroliberin 4

Thyrotropic hormone (TTH). Chemical structure: glicoprotein. This hormone is necessary for the normal functions of thyroid glands. Thyrotropic hormone promotes: accumulation of iodine in thyroid; including of iodine into the tyrosine; synthesis of thyroxine and triiodothyronine.

In difference to hormones of protein and peptide nature, receptors for steroid hormones are located within the cells - in the cytoplasm. From cytoplasm the hormone-receptor complexes is translocated into the nucleus where they interact with DNA of nuclear chromatin causing the activation of genes for respective enzyme proteins. So, if hormones of the first group cause the activation of existing enzyme molecules, the acting on the target cells of steroids and thyroid hormones results in the biosynthesis of new enzyme molecules.

CHEMISTRY STRUCTURE OF THYROID HORMONES:

Thyroxine and triiodthyronine are iodinated derivatives of amino acid tyrosine.

Formation and Secretion of Thyroglobulin by the Thyroid Cells. The thyroid cells are typical protein-secreting glandular cells. The endoplasmic reticulum and Golgi apparatus synthesize and secrete into the follicles a large glycoprotein molecule called thyroglobulin, with a molecular weight of about 335,000.

Each molecule of thyroglobulin contains about 70 tyrosine amino acids, and they are the major substrates that combine with iodine to form the thyroid hormones.

Transport of thyroxine and triiodothyronine to tissues: They combine mainly with Thyroxin-binding globulin <90% Thyroxin-binding pre-albumin Thyroxin-binding albumin.

MEHANISM OF ACTION OF THYROID HORMONES: The thyroid hormone receptors are either attached to the DNA genetic strands or located in proximity to them. The thyroid hormone receptor usually forms a heterodimer with retinoid X receptor (RXR) at specific thyroid hormone response elements on the DNA.

MEHANISM OF ACTION OF THYROID HORMONES: On binding with thyroid hormone, the receptors become activated and initiate the transcription process. Then large numbers of different types of messenger RNA are formed, followed within another few minutes or hours by RNA translation on the cytoplasmic ribosomes to form hundreds of new intracellular proteins

Functions of iodine containing hormones Necessary for normal growth, differentiation, sex and mental development Regulate the speed of metabolism 17

Effect of thyroxine and triiodthyronine on the protein metabolism: In physiological concentration stimulate the synthesis of proteins and nucleic acids. In the increased concentration activate the protein decomposition. Effect on lipid metabolism Activate the exit of lipids from depot, its decomposition and oxidation 18

Effect on carbohydrate metabolism Effect on energetic metabolism Accelerate the absorption of carbohydrates in the intestine Activate the decomposition of glycogen. Effect on energetic metabolism In excess thyroxin uncouples respiration and phosphorilation, decreases the ATP formation and increases the heat formation 19

Hypofunction of gland (occurs in the deficit of iodine in water, soil, air) Hypofunction in adults – mixedema Edema of mucosa Decrease of metabolism Decrease of body temperature mixedema 23

Hypofunction of gland (occurs in the deficit of iodine in water, soil, air) Decrease of metabolism Decrease of body temperature Hypofunction in childhood - cretinism Growth inhibition Unproportional body development Disorders of mental development cretinism 24

Endemic goiter (occurs in the deficit of iodine in water, soil and air) Connective tissue is enlarged in gland and it is increased in size markedly 25

Hyperfunction of gland – diffuse toxic goiter (thyrotoxicosis, Graves disease) Goiter – hyperplasia of gland Hypermetabolism Increase of body temperature Sweating, muscle weakness Weight loss with good appetite Tremor, emotional lability, insomnia Exophtalm 27