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GENERAL PRINCIPLES OF METABOLISM REGULATION. HORMONES. Levels of the homeostasis regulation Highest level – nervous system Intermediate hormonal regulation Intracellular (enzymes) Hormones – organic biologically active compounds of different chemical nature that are produced by the endocrine glands, enter directly into blood and accomplish humoral regulation of the metabolism of compounds and functions on the organism level. Hormonoids (tissue hormones) – compounds that are produced not in glands but in different tissues and regulate metabolic processes on the local level, but some of them (serotonin, acetylcholine) enters blood and regulate processes on the organism level. Specific stimulus for hormones secretion is: -nervous impulse -concentration of the certain compound in blood passing through the endocrine gland Endocrine glands: 1. 2. 3. 4. 5. 6. 7. of 8. 9. Hypothalamus Pituitary Epiphysis Thymus Thyroid gland Parathyroid glands Langergans’ islands pancreas Epinephrine glands Sex glands Classification of hormones according to chemical nature 1. 2. 3. 4. 5. Proteins: hormones of anterior pituitary (except ACTH), insulin, parathyroid hormone. Peptides: ACTH, calcitonin, glucagon, vasopressin, oxytocin, hormones of hypothalamus (releasing factors and statins). Derivatives of amino acids: catecholamins (epinephrine and norepinephrine), thyroxin, triiodthyronin, hormones of epiphysis. Steroid (derivatives of cholesterol): hormones of the cortex of epinephrine glands, sex hormones. Derivatives of polyunsaturated fatty (arachidonic) acids: prostaglandins. Fate of hormones in the organism •Are secreted directly into the blood •Peptide and protein hormones are secreted by exocytosis •Steroid (lipophilic) hormones continuously penetrate the membrane (they are not accumulated in cells, their concentration in blood is determined by the speed of synthesis) Transport of hormones in blood Protein and peptide nature – in free state Steroid hormones and hormones of thyroid gland – bound with alpha-globulins or albumins Catecholamines – in free state or bound with albumins, sulphates or glucuronic acid Reach the target organs Cells have the specific receptors to certain hormone Receptors of hormones Two groups: -placed on the surface of membrane – peptide and protein hormones, prostaglandins; -placed inside the cells (cytoplasm, nucleus) – steroid and thyroid hormones Model of the insulin receptor ( Jacobs, Cautrecasas, 1982) Inactivation of hormones After biochemical effect hormones are released and metabolized Hormones are inactivated mainly in liver Inactive metabolites are excreted mainly with urine Half-time life -from several min to 20 min – for the majority of hormones -till 1 h – for steroid hormones -till 1 week – for thyroid hormones THE FINAL EFFECTS OF HORMONES ACTION 1. 2. 3. 4. Change the permeability of cell membrane, accelerate the penetration of substrates, enzymes, coenzymes into the cell and out of cell. Acting on the allosteric centers affect the activity of enzymes (Hormones penetrating membranes). Affect the activity of enzymes through the messengers (cAMP). (Hormones that can not penetrate the membrane). Act on the genetic apparatus of the cell (nucleus, DNA) and promote the synthesis of enzymes (Steroid and thyroid hormones). It is located in the base of forebrain between thalamus and pituitary gland. Has wide anatomical bonds and collects information from another structures of brain. Collect information from blood flowing through hypothalamus. HYPOTHALAMUS Tight anatomical bonds with pituitary gland Two groups of hormones related to anterior and posterior lobes of pituitary Hypothalamus and posterior lobe of pituitary 3 peptides are synthesized Migrate along axons into posterior lobe of pituitary 1) Antidiuretic hormone (vasopressin) 2) Oxytocin 3) Neurophysin (promotes transport of vasopressin and oxytocin into pituitary gland) Hypothalamus and anterior pituitary Bound with anterior pituitary by the capillary net – hypothalamic portal system Releasing factors and statins rich the anterior pituitary via this system Secretion of liberins and statins by hypothalamus is carried out under the effect of nervous impulses and as result of the change of concentrations of certain hormones in blood (feedback regulation). Releasing factors (liberins) stimulate secretion of pituitary hormones; statins - inhibit. •somatoliberin, •thyroliberin, •corticoliberin, •foliliberin, •prolactoliberin, •luteinising-hormone liberin, •melanoliberin •somatostatin, •prolactostatin, •melanostatin HYPOPHISIS - “conductor of the hormonal orchestra of the organism” There are hormones of anterior, posterior and intermediate lobes of pituitary gland. The most important – anterior lobe (secrets tropic hormones) Tropic – because stimulate functions of peripheral endocrine glands TROPIC HORMONES OF PITUITARY Somatotropic hormone (growth hormone) Chemical nature – simple protein It is secreted continuously during the whole life Secretion is stimulated inhibited by somatostatin by somatoliberin, is Main function – stimulates somatic growth of organs and tissues, particularly bones, cartilages, muscles. Acts both directly and through the stimulation of the formation of polypeptides somatomedins (insulin-like growth factors). ILGF are synthesized in liver The effect of STH on the protein metabolism Promotes the entrance of AA into cells, Inhibits catabolism of proteins and AA Activates the synthesis of proteins, DNA, RNA. The effect of STH on the carbohydrate metabolism Antiinsulin hormone – activates insulinase of liver Activates the exit of glucose from liver Inhibits the conversion of glucose into fat The effect of STH on lipid metabolism Stimulates the decomposition of lipids (lipolisis) Stimulates the oxidation of fatty acids. In the inherited hypoplasia of pituatary gland dwarfism is developed. For the treatment GH is used. Hyperproduction of GH before puberty and before the completion of ossification results in gigantism Yao Defen, the tallest women in the life, 2.36 м Hyperfunction of pituitary inadults results in acromegaly – unproportionally intensive growth of particular body parts (fingers, nose, lower jaw, tongue, inner organs). Cause – tumor of anterior pituitary Adrenocorticotropic hormone (АCTH) Chemical nature – polipeptide Secretion is stimulated by corticoliberin Feedback regulation of the speed of secretion depending on the cortisol level Controls the cortex of epinephrine gland where cortisol is produced: -promotes the increase of cholesterol content in epinephrine glands cortex and its conversion into corticosteroids; -activates the passing of glucose into epinephrine glands and pentose phosphate cycle (NADPH synthesis) -has melanocyte stimulating activity Cushing’s disease Cushing's disease – hyperproduction of ACTH (adenoma in a pituitary gland) which in turn elevates cortisol. Obesity, particularly of the trunk and face (“moon face“) with sparing of the limbs; striae (stretches of the skin) Proximal muscle weakness Hirsutism (facial male-pattern hair growth) Insomnia, impotence, amenorrhoea, infertility Heart diseases, hypertension Polyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes) Kidney bones Depression, anxiety Hyperpigmentation Thyrotropic hormone (ТТH) Chemical structure – protein (glycoprotein) Secretion is stimulated by thyroliberin The speed of secretion is regulated according to the feedback regulation by thyroid hormones It is necessary for the normal functioning of thyroid gland: -promotes the accumulation of iodine in thyroid gland and its insertion into tyrosine; -stimulates the synthesis of try- and tetraiodthyronin Gonadotropic hormones Follicle-stimulating гормон Chemical nature – protein (glycoprotein) Secretion is stimulated by foliliberin Function: stimulates the function of follicles in women and spermatogenesis in men Luteinizing hormone Chemical nature – protein (glycoprotein) Secretion is stimulated by luliberin Function: stimulates the follicular growth and conversion of the follicle into a corpus luteum in women and secretion of testosterone in men Prolactin Chemical nature – protein Secretion is stimulated by prolactoliberin Functions: -stimulates the function of mammary glands (lactation); -provides the body with sexual gratification after sexual acts -stimulates the function of corpus luteum (progesterone secretion); -stimulates the growth of tissue of prostatic gland in men; -responsible for the mother instinct Lipotropic hormones Chemical nature – simple proteins Functions: -mobilization of lipids from depot; -melanocyte stimulating function; -decrease Ca in blood THE INTERMEDIATE LOBE OF PITUITARY Melanocyte stimulating hormone (melanotropin) Chemical nature – peptide Functions: -stimulates melaninogenesis; -adaptation of vision in darkness POSTERIOR LOBE OF PITUITARY Vasopressin (antidiuretic hormone) Chemical nature – peptide Functions: -activates hyaluronidase which decomposes hyaluronic acid in the membranes of kidney canaliculi – increases the reabsorption of water in kidneys; -contractions arterioles and capillaries – increases blood pressure Insufficiency – diabetes insipidus (polyuria, low density of urine, dehydratation) Oxytocin Chemical nature – peptide Functions: -stimulates the contraction of smooth muscles (of uterus during labor) -stimulates milk secretion (contraction of muscle fibers around mammary alveoli) Using: -for labor stimulation; -to stop after labor hemorrhage; -for stimulation of milk secretion EPIPHYSIS (PINEAL GLAND) Produces: Мelatonin from serotonin (regulates the pigment metabolism) Adrenoglomerulotropin – stimulates secretion of mineralocorticoids in the epinephrine glands cortex. Inhibitor of gonadotropin – inhibits the synthesis of prolactin, cholesterol PANCREAS Exocrine and endocrine parts Endocrine – Langerhans islets (alpha-, beta- and delta-cells) Alpha-cells: glucagon Beta-cells: insulin Delta-cells: somatostatin Epithelium of ducts: lipocain Insulin Nature – protein (51 АA) Is formed from proinsulin by proteolisis Contains zinc - Regulation of the synthesis: Glucose concentration in blood Other hormones (somatostatin) Sympathetic and parasympathetic nervous system It is destroyed by insulinase (enzyme of liver) Target cells: Hepatocytes Myocytes Adipocytes In the unsufficiency – diabetes mellitus The effect on carbohydrate metabolism •Increases the permeability of membranes for glucose •Activates glucokinase (hexokinase) in glycolysis •Activates TAC (citrate synthase) •Activates PPC (G-6-PDH) •Activates glycogen synthase •Activates pyruvate- and alpha-кetoglutarate dehydrogenase •Inhibits gluconeogenesis •Inhibits the decomposition of glycogen (glucose-6-phosphatase) Effect on the protein metabolism •Increases the permeability of membranes for AA •Activates synthesis of proteins and nucleic acids •Inhibits gluconeogenesis Effect on the lipid metabolism •Activates of the lipids synthesis •Promotes the saving of fats activating the decomposition of carbohydrates •Inhibits gluconeogenesis Effect on the mineral metabolism •Activates Na/K-АТP-аse Glucagon Nature – polypeptide Antagonist of insulin Synthesis is activated in fasting Functions Activates the decomposition of glycogen in liver Activates gluconeogenesis Inhibits glycolysis Activates lipolysis Somatostatin Nature – peptide Functions: • Inhibits secretion of insulin and glucagon • Inhibits secretion of STH and TTH • Inhibits secretion of local hormones of intestine Lipocain • • • Functions: Activates the synthesis of phospholipids in liver Stimulates the action of lipotropic factors Activates the oxidation of fatty acids in liver