Hormones PDF

HORMONES The endocrine system includes special glands whose cells function is to secrete chemical regulators, commonly referred to as hormones, into the internal media of the organism (blood, lymph). Hormones are produced in the gland cells, secreted into the blood or lymph and exercise con...

HORMONES The endocrine system includes special glands whose cells function is to secrete chemical regulators, commonly referred to as hormones, into the internal media of the organism (blood, lymph). Hormones are produced in the gland cells, secreted into the blood or lymph and exercise control over metabolism and development of the organism. General biological characters: Remote action Strict specificity of biological action (no hormone can be entirely replaced by another one) High biological acitivity (small amounts are sufficient for the vital activity of the organism) Hormone-secreting glands are: Central glands Peripheral glands  CENTRAL GLANDS Hypotalamus Neuropeptides Releasing hormones (liberins) Control of the secretion of the tropic hypophyseal Inhibitory hormones (statins) hormones Vasopressin, Control of the metabolism and function of the Oxytocin peripheral tissues and organs Pituitary Thyrotropin Control of the formation and secretion of hormones gland in the peripheral endocrine glands, Corticotropin Gonadotropin Follitropin Lutropin Prolactin (lactotropin) Somatotropin Partial involvement in direct metabolism in Melanotropin peripheral tissues and organs α and β lipotropins Vasopresin, oxytocin supplied from hypotalamus Epiphysis Melatonin Control of production of hypophyseal gonadotropin Adrenoglomerulotropin Control of aldosteron secretion in adrenal cortex  PERIPHERAL GLANDS Thyroid Iodotyronines (thyroxine, triiodothyronine) Action of the peripheral gland hormones on metabolism and Calcitonine functions of the peripheral tissues and organs Parathyroid Parathyrine Calcitonine Pancreas Insulin Glucagon Adrenal glands Cortex Corticosteroids: corticosterone, cortisol Aldosterone Estrogens, androgens Medulla Adrenalin (epinephrine), noradrenalin (norepinephrin) Sex glands Testes Androgens: testosterone, 5-α-dihidrotestosterone Ovaries Estrogens: estradiol, estrone, estriol Gestagens: progesterone Relaxin Placenta Estrogens, gestagens, testosterone, chorionic gonadotropin, placental lactogen, thyrotropin, relaxin Thymus Thymosin HORMONE-LIKE COMPOUNDS ENDOCRINE FUNCTIONS ARE ALSO EXERCISED BY OTHER SECRETING BIOLOGICALLY ACTIVE COMPOUNDS WHOSE PROPERTIES RESEMBLE THOSE OF HORMONES: HORMONE-LIKE COMPOUNDS OR HORMONOIDS OR LOCAL HORMONES OR PARAHORMONES. THEIR ACTION IS AT THE SITE THEY ARE PRODUCED. THEY ARE PRODUCED BY CELLS DISPERSED IN DIFFERENT TISSUES: – CELLS OF THE GASTROINTESTINAL TRACT (GASTRINE, SECRETINE) – INTESTINAL CHROMAFFIN CELLS ( SEROTONIN – REGULATOR OF THE INTETINAL FUNCTION) – MOST CELLS OF THE CONNECTIVE TISSUE (HEPARIN, HISTAMINE) – CELLS OF KIDNEYS, SEMINAL VESICLES (PROSTAGLANDINS  CHEMICAL STRUCTURE Protein-peptide hormones produced by Hypotalamus: regulatory hormones Pituitary gland: trop hormones Thyroid: calcitonin Parathyroid: parathyrine, calcitonin Pancreas: insulin, glucagon Aminoacid derivatives: Adrenalin derived from phenylalanine and tyrosine Iodothyronines derived from tyrosine Melatonin derived from tryptophan Steroids: Sex hormones: androgens, estrogens, gestagens Glucocorticoids Aldosterone  NEUROENDOCRINE RELATIONSHIP Neural input Hypothalamus Regulatory hormones (R, I) Posterior Oxytocin Primary Anterior pituitary gland pituitary gland Vasopressin target Tropic TSH ACTH FSH LH PRL GH MSH hormones Secondary Thyroid Adrenal Testes / ovaries target cortex estrogens thyroxine cortico- testosterone steroids gestagens Final Muscles, liver, Sex accesory Mamary Bones Skin target other tissues tissues glands  MUTUALLY EXCLUSSIVE RELATIONSHIP OF ENDOCRINE SYSTEM Nervous impulse Hypothalamus Releasing hormones Pituitary gland (liberins) Pituitary gland Peripheral hormones glands (tropic hormones) Short feed-back Peripheral Specific organs/ hormones Long feed-back cells Metabolites: Glucose Aminoacids Fatty acids, cholesterol Nucleotides, nucleosides Ca2+, Na+, K+, Cl-  HORMONAL CONTROL Extracellular regulators, including hormones, act as first messengers. Types of action: Membrane, local action Membrane intracellular, indirect action Cytosolic, direct action 1. MEMBRANE TYPE OF ACTION The hormone, at the site of its binding with the cell membrane, acts as an allosteric effector for membrane transport system and renders the membrane permeable to glucose, aminoacids, certain ions. The glucose and amino acids influence the biochemical cellular processes, while a change in ion partition on both sides of the membrane affects the electric potentioal and function of the cell. E.g. insulin  2. MEMBRANE-INTRACELLULAR TYPE OF ACTION The first messengers are not able to enter in the cell and cannot influence the intracellular processes directly. They act through a second messenger, intracellular, which triggers a chain of successive biochemical reactions leading to a modification of cellular functions. First messenger (hormone) reaches the receptor on the outer side of the cell membrane. The hormone-receptor complex acts on a protein (membrane transducer) The transducer transmits the signal to an enzyme (chemical amplifier) acting as a catalyst for the production of a second messenger inside the cell. The second messenger binds to a special protein (internal efector) which exerts an influence in the activity of a definite enzyme or on the properties of non-enzyme proteins (changes of the chemical rates, permeability, contractility, activation of genes) E.g. cAMP, cGMP, diacylglycerides, inositol-triphosphate, Ca2+, peptides  3. CYTOSOLIC MECHANISM OF ACTION Is typical for the compounds that can penetrate through the lipid layer of cell membrane, for example steroid hormones, vitamin D The hormone forms a complex with a cytosolic or nuclear receptor By selectively affecting the gene activity of nuclear chromosomes and exerting influence on the metabolism and function of cell, the hormone-receptor complex controls the enzyme concentration in the cell E.g. iodothyronine have a combined type of action, both intracellular-membrane and cytosolic  PROHORMONES Polypeptide hormones are synthesized as inactive prohormones (hormonogens). They become active after the extracellular activation by the peptidases Prohormone Source Proinsulin pancreas Proparathyroid hormone parathyroid Angiotensinogen liver Progastrin stomach HORMONES OF HYPOTHALAMUS-HYPOPHYSEAL SYSTEM HORMONES OF HYPOPHYSIS IN THE ANTERIOR LOBE OF PITUITARY GLAND (ADENOHYPOPHYSIS) TROPIC HORMONES ARE PRODUCED FROM THE POSTERIOR LOBE (NEUROHYPOPHYSIS) NEUROHORMONES PRODUCED IN THE HYPOTHALAMUS ARE RELEASED: OXYTOCIN, VASOPRESSIN STRUCTURE: THYROTROPIN, FOLLITROPIN, LUTROPIN – GLYCOPROTEINS VASOPRESSIN, OXYTOCIN – CYCLIC OCTAPEPTIDES HORMONES OF HYPOTHALAMUS-HYPOPHYSEAL SYSTEM Hypothalamic hormones Tropic hormones Releasing factors Inhibiting factors Somatoliberin Somatostatin Somatotropin Thyreoliberin Thyreotropin Corticoliberin Corticotropin Folliliberin Follitropin Luliberin Lutropin Prolactoliberin Prolactostatin Prolactin Melanoliberin Melanostatin Melanotropin MECHANISM OF ACTION OF HYPOPHYSEAL HORMONES Tropic hormones exert their function on the peripheral glands or directly on the peripheral tissues by binding on the membrane receptors and activating adenylate cyclase. cAMP determines the effects in the target cells: Control of biosynthesis and hormonal secretion by peripheral glands (thyrotropin, corticotropin, follitropin, lutropin, prolactin, somatotropin) Control of sex cell production (follitropin) Control of effector tissues (corticotropin, lutropin, follitropin, prolactin, somatotropin, melanotropin, oxytocin, vasopressin) Control of the nervous system (corticotropin)  DIRECT EFFECT ON PERIPHERAL TISSUES Corticotropin (ACTH): adenylate cyclase activation; cAMP activates the lipase → release of fatty acids and glycerol (direct action on fat tissue by stimulating the tissue’s glucose absorption and fat mobilizing); action on melanin production  and  lipotropins: fat mobilizing action (cAMP mechanism) Gonadotropins: Fat mobilizing (cAMP) Prolactin protein and lactose synthesis by mamary gland epithelium Melanotropin: Production of melanin in the skin, iris, epithelial pigment in retina Fat-mobilizing (cAMP) Somatotropin/ growth hormone (STH, GH): Only hormone with species-specific effect Stimulates cartilage cell division, growth of bones in length, internal organs, soft tissue of face and oral cavity Stimulates secretion of glucagon more than insulin Defficiency – dwarfism proportionate constitution, no mental retardation Hypersecretion – gigantism or acromegalia  Vasopressin or antidiuretic hormone (ADH): Fat mobilizing action Selective control of water reabsorption in the distal tubes and collecting ducts of the kidneys and activates adenylate cyclase; cAMP activates protein kinases that phosphorilate the proteins in the membranes to increase the permeability for water; reduces diuresis,  density and Na+ and Cl- urinary concentration.  contraction of muscles in arterioles and capillaries and determine moderate  in blood pressure Deficiency : diabetes insipidus ( large discharge of urine (4- 10L/day), low density, polydipsia Oxytocin:  contraction of uterine muscles,  Ca2+ intracellular, cAMP,  synthesis of protein in mamary glands during lactation  the release of milk –  contractility of myoepithelium of mamary ducts Insulin-like effect on fat tissue ( G consumption and TG synthesis) THYROIDAL HORMONES IODOTHYRONINES: – TRIIODOTHYRONINE (T3) – TETRAIODOTHYRONINE = THYROXINE (T4) FUNCTION: – CONTROL THE ENERGY METABOLISM – EXERT INFLUENCE ON CELL DIVISION AND DIFFERENTIATION CALCITONIN - POLIPEPTIDE MW 30,000 FUNCTION: CONTROL OF CALCIUM-PHOSPHORUS METABOLISM HYPERFUNCTION = HYPERTHYROIDISM THE ACUTE DISEASE = THYROTOXICOSIS = BASEDOW’S DISEASE T3 IS PREDOMINANT ACCELERATED CATABOLISM OF CARBOHYDRATE, TRIACYLGLYCERIDES, PROTEINS. INCREASED BASAL METABOLISM ELEVATED BODY TEMPERATURE LOSS OF BODY WEIGHT TACHYCARDIA HYPEREXCITABILITY EXOPHTALMOS (PROTRUSION OF THE EYEBALLS) HYPOFUNCTION = HYPOTHYROSIS IN CHILD: INFANTILE MYXEDEMA, CRETINISM = INEFFECTIVE ACTION OF THE HORMONES ON CELL DIVISION AND CELL DIFFERENTIATION – PHYSICAL RETARDATION WITH DISPROPORTIONATE CONSTITUTION DUE TO IMPROPER GROWTH OF BONE TISSUE, – EXTREME MENTAL RETARDATION DUE TO IMPARED DIFFERENTIATION OF THE NEURONS – BASAL METABOLISM REDUCED, BODY TEMPERATURE BELOW NORMAL IN ADULT: MYXEDEMA MANIFESTED IN – REDUCED BASAL METABOLISM, LOWERED BODY TEMPERATURE – LESS RETENTIVE MEMORY – IMPAIRED RENEWAL OF DERMAL EPITHELIUM (DRY SKIN) – DEPOSITION OF MUCOID MATERIALS IN SUBCUTANEOUS FAT PARATHYROID GLANDS CALCITONINE (ALSO SECRETED BY THYROID GLAND) – PROTEIN OF 32 AA PARATHYRINE (PARATHORMONE, PTH) – 84 AA FUNCTION: CONTROL THE BALANCE OF CALCIUM AND ORGANIC PHOSPHATE DYSFUNCTION OF PARATHYROIDS HYPOFUNCTION = HYPOPARATHYROSIS = DETERMINE REDUCED CA2+ CONCENTRATION IN THE BLOOD AND EXTRACELLULAR FLUID, THAT FACILITATES THE NA+ FLOW INTO THE CELL, INCREASING THE EXCITABILITY OF NERVE AND MUCLE CELLS = HYPEREXCITABILITY OF THE NEUROMUSCULAR SYSTEM (CONVULSIVE CONTRACTION OF MUSCLES) HYPERPARATHYROSIS = – MOBILIZATION OF ENDOGENIC CALCIUM FROM BONES (RISK OF FRACTURE); – CALCEMIA IS INCREASED, – PHOSPHATE LOWER; – CALCIUM IS DEPOSITED IN THE INTERNAL ORGANS (CALCIFICATION OF BLOOD VESSELS, KIDNEY, GASTROINTESTINAL TRACT, LIVER) PANCREAS HORMONES CELLS OF LANGERHANS ISLANDS – A-TYPE (Α-CELLS) SECRETE GLUCAGON – B-TYPE (Β-CELLS) SECRETE INSULIN – D-TYPE SECRETE SOMATOSTATIN – PP-TYPE (F-CELLS) SECRETE PANCREATIC POLYPEPTIDE (THAT IS PRODUCED IN THE ACINOUS TISSUE, TOO) GLUCAGON Polypeptide with MW 3485, composed of 29 aa Produced by the α-cells as proglucagon (37aa) which is hydrolysed by proteases to generate the active glucagon Secretion is increased by Ca2+ and arginine inhibited by glucose and somatostatin  GLUCAGON MECHANISM OF ACTION TARGETS: LIVER, FAT TISSUE, MUSCLE BINDS TO THE MEMBRANE RECEPTORS, ACTIVATES THE ADENYLATE CYCLASE, INCREASE THE CAMP THAT STIMULATES – THE MOBILIZATION OF GLYCOGEN IN THE LIVER AND MUSCLES AND – TRIGLYCERIDES IN THE FAT TISSUE. THUS THE CONCENTRATION OF GLUCOSE↑, GLYCEROL↑, FATTY ACIDS ↑ THE CATABOLISM OF FA PRODUCE A LARGE AMOUNT OF ACETYL- COA AND KETONE BODIES (KETONEMIA, KETONURIA) IN THE LIVER IT INHIBITS THE PROTEIN SYNTHESIS AND FACILITATES THE PROTEIN BREAKDOWN. THE AA ARE USED IN – UREA PRODUCTION AND – GLUCONEOGENESIS → GLUCOSE ↑  INSULIN SECRETED BY Β-CELLS AS PRE-PROINSULIN WHICH IS HYDROLYSED AND GENERATES THE PROINSULIN (84 AA); THIS IS CLEAVED INTO PEPTIDE-C (33 AA) AND INSULIN (51 AA) WITH MW ABOUT 6000 COMPOSED OF 2 POLYPEPTIDE CHAINS – A-CHAIN OF 21 AA, WITH A DISULPHIDE BOND (-S-S-) BETWEEN CYS IN POSITION 6 AND CYS IN POSITION 11 AND C-TERMINAL ASPARAGINE, ESSENTIAL FOR THE BIOLOGICAL ACTIVITY – B-CHAIN OF 30 AA – LINKED THROUGH DISULPHIDE (-S-S-) BRIDGES BETWEEN: –CYS IN POSITION 7 ON A-CHAIN AND 7 ON B-CHAIN –CYS IN POSITION 20 ON A-CHAIN AND 19 ON B-CHAIN THE SECRETION IS INCREASED BY GLUCOSE AND CA2+, ASPARAGINE AND LEUCINE,  INSULIN MECHANISM OF ACTION INSULIN EXISTS AS: – FREE INSULIN - INFLUENCES ALL THE INSULIN-SENSITIVE TISSUES (MUSCLES, CONNECTIVE TISSUE, INCLUDING FAT TISSUE) AND – BOUND TO PLASMA PROTEINS – INFLUENCES ONLY FAT TISSUE; – LESS SENSITIVE IS THE LIVER; NOT SENSITIVE IS THE NERVOUS TISSUE INSULIN BINDS TO MEMBRANE RECEPTOR (A GLYCOPROTEIN) THE INSULIN-RECEPTOR COMPLEX CHANGES THE PERMEABILITY OF THE MEMBRANE FOR THE GLUCOSE, AMINOACIDS, CA2+, K+, NA+, ACCELERATING THEIR TRANSPORT INTO THE CELL. PEPTIDE SECOND MESSENGER(S) ACTIVATE CAMP-PHOSPHO-DIESTERASE, DECREASING CAMP, THAT INHIBITS THE GLYCOGENOLYSIS, GLUCONEOGENESIS, LIPOLYSIS, KETOGENESIS A LOWER CAMP/CGMP RATIO FACILITATES THE GLYCOGENOGENESIS, LIPOGENESIS, PROTEIN SYNTHESIS THROUGH CGMPAND CA2+ ACCELERATES THE DNA SYNTHESIS (REPLICATION) AND RNA (TRANSCRIPTION), FAVORING THE PROLIFERATION, GROWTH AND DIFFERENTIATION OF CELLS THE RESULT IS AN ANABOLIC ACTION WITH A POSITIVE NITROGEN BALANCE:: – IN BLOOD: GLUCOSE↓, FA↓, GLYCEROL↓, AMINOACIDS↓, K+↓ – IN URINE: AMINOACIDS↓, K+↓, DISTURBANCES OF ENDOCRINE PANCREAS EXCESSIVE INSULIN IN INSULINOMES (TUMOURS WITH Β-CELLS) OR IN OVERDOSE IN INSULIN THERAPY → HYPOGLYCEMIA → SYNCOPAL STATES, CONVULSIONS, FATAL OUTCOME DEFICIENT INSULIN → DIABETES MELLITUS: – HYPERGLYCEMIA (G↑), GLYCOSURIA – FA, GLYCEROL, CHOLESTEROL↑ – HYPERAMINOACIDEMIA, HYPERAMINOACIDURIA – KETONEMIA, KETONURIA → ACIDOSIS → FATAL OUTCOME PRACTICAL APPLICATION OF INSULIN: – TREATMENT OF DIABETES MELLITUS – ANABOLIC STIMULATORS IN DYSTROPHY OF ORGANS, MALNUTRITION, INANITION – RESTORATION OF METABOLISM AFTER HEAVY MUSCULAR WORK  HORMONES OF ADRENAL GLANDS ADRENAL MEDULLA PRODUCES AND STORES INTO CHROMAFFIN CELLS – ADRENALIN / EPINEPHRIN – NORADRENALIN / NOREPINEPHRIN ADRENALIN SECRETION IS INFLUENCED BY – HYPOGLYCEMIA – STRESS (PHYSIOLOGIC ACTIVITY OF THE ORGANISM INCREASES FASTER THAN THE ADAPTIVE RESPONSES) EFFECT ON ADRENORECEPTORS – Α → STIMULATES THE GUANIDINE CYCLASE → CGMP – Β → STIMULATES THE ADENYLATE CYCLASE → CAMP CAMP HAS A SIMILAR EFFECT AS GLUCAGON ON THE LIVER, MUSCLE, FAT TISSUE AFFECTS THE FUNCTION OF CARDIOVASCULAR SYSTEM (AMPLITUDE AND FREQUENCY OF HEART CONTRACTION ↑, BLOOD PRESSURE ↑) RELAXES SMOOTH MUSCLES OF THE INTESTINE, BRONCHI, UTERUS. HORMONES OF ADRENAL GLANDS ADRENAL CORTEX PRODUCES STEROID HORMONES (CORTICOSTEROIDS) SUBDIVIDED IN: GLUCOCORTICOSTEROIDS – AFFECTING THE CARBOHYDRATE METABOLISM – HYDROCORTISONE – CORTICOSTERONE MINERALOCORTICOSTEROIDS -AFFECTING THE MINERAL METABOLISM – ALDOSTERONE SEX HORMONES (ANDROGENS, ESTROGENS) IN SMALL AMOUNTS GLUCOCORTICOIDS: HYDROCORTISONE, CORTICOSTERONE CONTROLLED BY CORTICOTROPIN RELEASED FROM THE PITUITARY GLAND AS A RESPONSE TO STRESS; IT IS BOUND TO THE ADRENOCORTICAL CELL MEMBRANE, STIMULATES THE PRODUCTION OF CAMP, TRIGGERING THE DELIVERY OF CHOLESTEROL ESTERS FOR THE SYNTHESIS OF GLUCOCORTICOIDS; THEY INHIBIT THE CORTICOTROPIN (NEGATIVE FEED-BACK MECHANISM) MECHANISM OF ACTION: – TRANSPORTED IN THE PLASMA BY TRANSCORTIN (PROTEIN) – TARGETS: LIVER, KIDNEY, LYMPHOID TISSUE (SPLEEN, LYMPH NODES, LYMPHOID PLAQUES IN THE INTESTIN, LYMPHOCYTES, THYMUS), CONNECTIVE TISSUE (BONES, SUBCUTANEOUS TISSUE, ADIPOSE TISSUE) MUSCLE RESULT: – IN THE BLOOD: GLUCOSE, FATTY ACIDS, GLYCEROL, AMINOACIDS, KETONE BODIES↑ – IN URINE: GLUCOSE, AMINOACIDS, KETONE BODIES↑ – IN THE KIDNEYS: ↑ NA+ REABSORPTION, K+ EXCRETION; – NA AND H2O ARE RETAINED IN EXTRACELLULAR SPACE (EDEMA) – IN BONES: ↓ PROTEIN SYNTHESIS, DEOSSIFICATION, CA AND P →BLOOD →URINE MINERALCORTICOIDS ALDOSTERONE SECRETION IS CONTROLED BY NA+ AND K+ (STIMULATED BY LOW NA+ AND HIGH K+ CONCENTRATION) IT IS BELIEVED THAT THE EPIPHYSIS PRODUCES A TROPIC HORMONE = ADRENOGLOMERULOTROPIN THAT STIMULATES THE SECRETION MECHANISM OF ACTION: – TRANSPORTED IN THE BLOOD → TISSUE USING PLASMA ALBUMINS – TARGET: EPITHELIAL CELLS OF THE DISTAL TUBULES OF THE KIDNEY – BOUND TO RECEPTOR, THE COMPLEX PENETRATES THE NUCLEUS ACTIVATING THE TRANSCRIPTION OF THE GENES THAT CARRY INFORMATION REFERRING TO A PROTEIN INVOLVED IN THE TRANSPORT OF NA+ ACROSS THE MEMBRANE OF TUBULAR EPITHELIUM: ↑ REABSORPTION OF NA+ , CL- AND WATER FROM THE URINE TO THE INTERCELLULAR FLUID AND TO THE BLOOD AND ↑ EXCRETION OF K+ IN THE URINE DISTURBANCES OF ADRENAL GLANDS HYPERFUNCTION = HYPERCORTICOIDISM – CUSHING'S DISEASE (HYPERSECRETION OF CORTICOTROPIN) “STEROID” DIABETES, ATROPHY OF SUBCUTANEOUS CONNECTIVE TISSUE OSTEOPOROSIS HYPERTENSION (DUE TO SECONDARY INCREASE OF ADRENALIN AND NORADRENALIN) – HYPERALDOSTERONISM (KONN'S DISEASE) EDEMA, HIGH BLOOD PRESSURE, MYOCARDIAL HYPEREXCITABILITY HYPOFUNCTION = HYPOCORTICOIDISM = ADDISON'S DISEASE – GLUCOCORTICOID DEFICIENCY: REDUCED RESISTANCE TO EMOTIONAL STRESS AND INFECTIONS, CHEMICAL, MECHANICAL FACTORS; IT DETERMINES HYPOGLYCEMIA – ALDOSTERONE DEFICIENCY: DISTURBED WATER-SALT IMBALANCE - LOSS OF NA+, H2O AND ACCUMULATION OF K+ → HYPOTENSION, MYASTENIA, PROGRESSIVE FATIGABILITY, LOW MUSCULAR EXCITABILITY PRACTICAL USE OF CORTICOSTEROIDS TREATMENT OF ALLERGIC AND AUTOIMMUNE DISEASES: RHEUMATISM, COLLAGENOSES, NONSPECIFIC ARTHRITES, BRONCHIAL ASTMA, DERMATOSES DESENSITIZING ANTIINFLAMMATORY IMMUNODEPRESSIVE AGENTS (PROPHYLAXIS OF REJECTION OF TRANSPLANTED ORGANS)