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Dr. Areej M. Al-Taweel Pharmacognosy Department Chemical Classification of Hormones A- Steroidal Hormones: 1- Adrenocorticoids: Glucocorticoids Mineralocorticoids e.g. Hydrocortisone. e.g. Aldosterone. 2- Sex Hormones: Female sex hormones Male sex hormones e.g. Estrogens and Progestins e.g. Androgens. B- Amino acids derived hormones: 1- Hormones derived from single amino acid e.g. Thyroxin. 2- Peptide hormones: i- Only amino acids: *Anterior Pituitary hormones: - Prolactin - Growth Hormone - Placental lactogen. * Corticotropins: Adrenocorticotropic hormone ACTH. * Insulin * Parathyroid hormone and Calcitonin. ii- Glycoproteins (Amino acids and sugars): *Anterior Pituitary Hormones: - Leuteinizing hormone (LH) -Follicle Stimulating hormone (FSH) - Chorionic Gonadotropin (CG) -Thyroid Stimulating hormone (TSH). Mechanisms of Hormonal Actions I- Peptide Hormones Peptide hormones do not enter the cell but bind to plasma membrane receptors. ■ ■ Peptide hormones combine with membrane receptors that activate signal transduction. Many hormones use a G protein-linkedadenylyl cyclase-cAMP second messenger. Second messengers activate other intracellular chemicals to produce the target cell response. II-Steroid Hormones ■ Once inside the cell the steroid hormone binds with a specific receptor found only in the cytoplasm of the target cell. The receptor bound steroid hormone then travels into the nucleus. The activated hormone-receptor complex binds to DNA and initiates transcription of a particular gene. The result is production of messenger RNA followed by protein synthesis. (new protein produce change in cellular activity) Thyroid Hormones Thyroid Gland: Highly vascular flat structure. Located at the upper portion of the trachea. Composed of twp lobes. Hormones of the Thyroid gland: Thyroid gland secretes Thyroxin T4 and lesser amounts of triiodothyronine (T3). Calcitonin. Thyroxin and Tiiodothyronin * Structures: Derived from single amino acid. I HO I NH2 CH2CH COOH O I I Thyroxine I 5' HO NH2 CH2CH COOH O I I Triiodothyronine Structure Activity Relationship Angle between the two aromatic rings must be 1200. 3’-Monosubstituted molecules are more active than 3’, 5’disubstituted ones. Triiodothyronin is 4 times more active than Thyroxin. 3’-Isopropyl derivative is 7 times more active than Thyroxin. Regulation: Hypothalamus Thyrotropine Releasing Hormone (TRH) Anterior Pituitary Thyroid Stimulating Hormone (TSH) Thyroid gland Thyroxin & Triiodothyronin Stimulation: TRH Inhibition: -ve Feed-back mechanism. When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH. Actions of the Thyroid Hormones: Enhance growth and protein synthesis. Essential for the development of the nervous system. Increase oxygen consumption and basal metabolic rate. Increase body temperature. Cardiovascular effect: Increase heart rate. Increase force of contraction. Increase cardiac output. Disorders of thyroid function include: * Hypothyrodisim - In infants, cretinism - In adults this cause myxoedema * Hyperthyrodisim either: - Diffuse toxic goiter - Toxic nodular goiter Disorders of thyroid function Hypothyroidism in children (Cretinism) Cretinism: Irreversible condition due to deficiency of thyroxin soon after birth. Retardation in physical and mental development. Sign and symptoms of Cretinism: - Mental retardation - Large head - Swollen eye lids - Flattened nose - Temperature below normal - Enlarged tongue - Grows very slowly. - Poor metabolism - Thick, dry, cool skin Disorders of thyroid function Hypothyroidism (Adult) Myxoedema: Deficiency of thyroxin in adults due to: Removal of thyroid gland by surgery. Destruction of the gland by Radioactive Iodine. Atrophy of the thyroid gland. Symptoms of Myxedema: Muscle weakness. Slow heart rate and low cardiac output. Dry cold and thick skin. Brittle coarse hair. Puffy expressionless face. Decreased sweating Increase body weight and body fat Treatment: Thyroxin for life. eg. :L-Thyroxin sodium (Synthyroid)