Endocrine System Lecture Notes PDF

ENDOCRIN E SYSTEM  ONE OF THE CHEMICAL MESSENGER BODY REGULATORY SYSTEMS.  IT COMPRISES GLANDS AND CELLS THAT MAKE & SECRETE ENDOCRINE DR LSK HORMONES. FUNCTIONS OF ENDOCRINE SYSTEM It...

ENDOCRIN E SYSTEM  ONE OF THE CHEMICAL MESSENGER BODY REGULATORY SYSTEMS.  IT COMPRISES GLANDS AND CELLS THAT MAKE & SECRETE ENDOCRINE DR LSK HORMONES. FUNCTIONS OF ENDOCRINE SYSTEM It regulates the internal body environment, e.g blood pressure and blood glucose levels It controls and integrates the reproductive system Maintenance of water and electrolyte balance Growth and development Regulation of cellular metabolism e.g body's basal metabolic rate is controlled by the thyroid hormones thyroxine (T4) and triiodothyronine (T3) Mobilisation of body defences e.g epinephrine & norepinephrine, also thymus produces t-cell  INTRODUCTION  Hormones are regulatory chemical messengers secreted by glands/cells into the Cell blood or fluid around with recept cells to regulate body or activities upon acting on target cell/organ.  Endocrine hormones Endocrine are hormones secreted system (eku.edu) into the blood by Difference between endocrine and exocrine endocrine glands/cells glands??? to regulate activities of Body regulatory systems – Endocrine and distant target nervous systems cell/organ. Classical definition of hormones???  EXOCRINE AND ENDOCRINE GLANDS They have They are ducts !!! ductless !!! Secrete their product to an epithelial surface via Endocrine = Greek terms duct "endo = within; krine= to an external separate or secrete. secretion, outside its source via duct E.g., sweat, sebaceous, mammary Endocrine sys secrete into & digestive enzyme body internal environment glands. (the blood)  BODY REGULATORY SYSTEMS - RELATIONSHIP BETWEEN NERVOUS AND ENDOCRINE SYSTEMS Feature Nervous sys Endocrine sys Transmission Electrical impulses & Chemical signal (hormones) type neurotransmitters (chemicals ) Transmission Through neurons Blood means Transmission Fast Slow speed Response Fast (↓ reaction time, RT) (↑ reaction time) Effect duration Short lived Short or long Type of action Voluntary or involuntary Involuntary Target Localized Mostly diffused & distant Structures CNS, PNS Glands  MAJOR ENDOCRINE GLANDS Koeppen & Stanton, 2010. Berne and Levy Physiology, 6th ed., ENDOCRINE GLANDS, HORMONES, AND THEIR FUNCTIONS & STRUCTURE Gland/ Hormones Major Functions Chemic Tissue al Structu re Hypothalamu Thyrotropin- → secretion of thyroid-stimulating hormone Peptide s releasing (TSH or thyrotropin) & prolactin Hormone (TRH) Corticotropin- → release of adrenocorticotropic hormone Peptide releasing (ACTH) Hormone (CRH) Growth hormone- → release of growth hormone Peptide releasing Hormone (GHRH) Growth H inhibitory Inhibits release of growth hormone Peptide hormone (somatostatin) Gonadotropin- → release of luteinizing hormone (LH) & Peptide releasing follicle-stimulating hormone (FSH) Hormone (GnRH)  ENDOCRINE GLANDS, HORMONES, AND THEIR FUNCTIONS & STRUCTURE Gland/ Hormones Major Functions Chemic Tissue al Structu re Anterior Growth hormone → protein synthesis & overall growth Peptide pituitary (GH) Thyroid-stimulating → synthesis and secretion of thyroid Peptide Hormone (TSH) hormones (thyroxine and triiodothyronine) Adrenocorticotropic → synthesis and secretion of adrenocortical Peptide Hormone (ACTH) hormones (cortisol, androgens, and aldosterone) Prolactin promotes female breast development & milk Peptide secretion Follicle-stimulating → follicle growth in the ovaries and Peptide Hormone (FSH) sperm maturation in Sertoli cells of testes Luteinizing hormone → testosterone synthesis in Leydig cells of Peptide (LH) testes; → ovulation; → formation of corpus luteum, → estrogen & progesterone synthesis in ovaries. ENDOCRINE GLANDS, HORMONES, AND THEIR FUNCTIONS & STRUCTURE Gland/ Hormones Major Functions Chemic Tissue al Structu re Thyroid Thyroxine (T4) and ↑ the rates of chemical reactions in most cells, Amine triiodothyronine (T3) thus ↑ body metabolic rate. Calcitonin Promotes deposition of Ca in the bones & ↓ Peptide ECF [Ca2+] Parathyroid Parathyroid hormone Controls serum calcium ion concentration by Peptide increasing calcium absorption by the gut and kidneys and releasing calcium from bones Adrenal Cortisol Controls protein, carbohydrate, & fat Steroid cortex metabolism; it is anti-inflammatory. Aldosterone ↑ renal Na reabsorption, K secretion, & H Steroid secretion Adrenal Norepinephrine, Sympathetic activity Amine medulla epinephrine Sympathetic activity Pancreas Insulin (beta cells) Promotes glucose entry in many cells, and in Peptide ENDOCRINE GLANDS, HORMONES, AND THEIR FUNCTIONS & STRUCTURE Gland/ Hormones Major Functions Chemic Tissue al Structu re Testes Testosterone Promotes development of male reproductive Steroid system and male secondary sexual characteristics ovaries Estrogens Promotes growth and development of female Steroid reproductive system, female breasts, and female secondary sexual characteristics Progesterone Stimulates secretion of “uterine milk” by the Steroid uterine endometrial glands and promotes development of secretory apparatus of breasts Placenta Human chorionic Promotes growth of corpus luteum and Steroid gonadotropin secretion of estrogens and progesterone by corpus luteum Human Probably helps promote development of some Steroid Somatomammotropi fetal tissues, as well as the mother’s breasts  ENDOCRINE GLANDS, HORMONES, AND THEIR FUNCTIONS & STRUCTURE Gland/ Hormones Major Functions Chemic Tissue al Structu re Kidney Renin Catalyzes conversion of angiotensinogen to Peptide angiotensin I (acts as an enzyme). 1,25- Increases intestinal absorption of calcium and Steroid Dihydroxycholecalcif bone mineralization erol Erythropoietin Increases erythrocyte production Peptide Heart Atrial natriuretic Increases sodium excretion by kidneys, Peptide peptide reduces blood pressure Stomach Gastrin Stimulates hydrogen chloride secretion by Peptide parietal cells Small Secretin Stimulates pancreatic acinar cells to release Peptide intestine bicarbonate and water Cholecystokinin Stimulates gallbladder contraction and release Peptide SECRETION OF POSTERIOR PITUITARY HORMONES OXYTOCIN  SYNTHESIS OF OXYTOCIN Oxytocin is synthesized in the cell bodies of hypothalamic neurons (paraventricular nucleus) Oxytocin is stored in the posterior pituitary  FUNCTIONS OF OXYTOCIN  Oxytocin is a strong stimulant of uterine contraction  Regulated by a positive feedback mechanism  This leads to increased intensity of uterine contractions, ending in birth  Oxytocin triggers milk ejection (“letdown” reflex) Contracts the myoepithelial cells of the alveoli  Increases contraction of smooth muscle of the vas deferens, helping in the ejaculation process. ANTIDIURETIC HORMONE (ADH) (VASOPRESSIN)  SYNTHESIS OF ADH  ADH synthesized in the cell bodies of hypothalamic neurons (supraoptic nucleus)  ADH is stored in the posterior pituitary  in the absence of ADH, the collecting tubules and ducts become almost impermeable to water  Which allows extreme loss of water into the urine  When ADH binds to its receptor, it activates the translocation of vesicles containing aquaporins to the apical cell membranes  CONTROL OF ADH RELEASE 1. Increased Extracellular Fluid Osmolarity Stimulates ADH Secretion:  Osmoreceptors in or near the hypothalamus:  osmotic pressure  ADH secretion   osmotic pressure   ADH secretion 2. Low Blood Volume and Low Blood Pressure Stimulate ADH Secretion —Vasoconstrictor Effects of ADH:  Baroreceptor in carotid artery and aortic arch, and left atrium:   blood pressure   ADH secretion  blood pressure   ADH secretion 3. Physiological stress: pain, fear, trauma, and stress stimulate ADH release.  REGULATION OF ADH Hypothalamus receives feedback from: Osmoreceptors Aortic arch baroreceptors Carotid baroreceptors Atrial stretch receptors Any increase in osmolality or decrease in blood volume will stimulate ADH secretion from posterior pituitary.  Increased ADH Blood V1 receptor Pressure  ADH DISORDERS  Diabetes Insipidus: Neurogenic (central): (failure of hypothalamus or neurohypophysis to synthesize or secrete ADH) Nephrogenic: (failure of the kidney to respond appropriately to ADH)  Syndrome of Inappropriate Antidiuretic Hormone (SIADH)  DIABETES INSIPIDUS  DI is a disorder resulting from deficiency of anti-diuretic hormone (ADH) or its action and is characterized by the passage of copious amounts of dilute urine.  It must be differentiated from other polyuric states such as primary polydipsia & osmotic duiresis. Central DI is due to failure of producing adequate ADH.  DIABETES INSIPIDUS  Nephrogenic DI results when the renal tubules of the kidneys fail to respond to circulating ADH.  The resulting renal concentration defect leads to the loss of large volumes of dilute urine. This causes cellular and extracellular dehydration and hypernatremia.  TREATMENT  DESMOPRESSIN (DDAVP): A SYNTHETIC ANALOG IS SUPERIOR TO NATIVE AVP BECAUSE:  IT HAS LONGER DURATION OF ACTION (8-10 h vs 2-3 h)  MORE POTENT, ITS ANTIDIURETIC ACTIVITY IS 3000 TIMES GREATER THAN ITS PRESSOR ACTIVITY  TREATMENT OF NEPHROGENIC DI  CORRECTION OF UNDERLYING CAUSE  PROVISION OF ADEQUATE FLUIDS & CALORIE  LOW SODIUM DIET  DIURETICS  HIGH DOSE OF DDAVP SUMMARY OF POSTERIOR PITUITARY HORMONES ACTIONS   Hypothalamus receive many nervous signals e.g., pain, emotion, olfactory. NERVOUS AND ENDOCRINE SYSTEMS WORK TOGETHER  Also, the hypothalamus receives substances (e.g., nutrients, electrolytes, H2O, hormones) from blood.  Those substances from blood excite or inhibit various portions of the hypothalamus.  Then, hypothalamus contributes to endocrine system via regulation of pituitary gland secretion. Endocrine cells (Blood vessel) Neurohorm Neurohormone- one- ADH, hypophysiotropic oxytocin  TROPIC HORMONES, NON-TROPIC HORMONES AND TROPHIC HORMONES  Tropic hormones have other endocrine glands as their target.  usually act in the beginning of the reaction stimulating other endocrine gland to eventually release non-tropic hormones. E.g.  Hypothalamic hormones to anterior pituitary.  FSH, LH, ACTH, and TSH of anterior pituitary to other glands.  Non-tropic hormones directly stimulate target cells to induce effects.  They act in the end of the chain reaction mainly on non-endocrine target. e.g., cortisol, ADH, estrogen, testosterone etc.  Trophic hormones stimulate growth, function, or nutrition of other endocrine cells.  They may lead to hypertrophy (increase in cell size) or hyperplasia (increase in cell number).  E.g., TSH, ACTH, LH, FSH, gastrin (causes stomach mucosa growth). CLASSIFICATION OF HORMONES – BASED ON CHEMICAL STRUCTURE HORMONE Steroids S Nonsteroi Cortisol ds Proteins (pp with Glycoprot Aldosteron a.aH,>100) eins e Growth Prolactin, ACTH, FSH, LH, TSH, Human Estrogen Calcitonin, Parathyroid H, chorionic gonadotropin Progester Insulin, Glucagon one polypeptides (pp. have Amino acid derivatives a.a 99 % of thyroid hormones are transported in the blood is bound to plasma proteins. Protein-bound hormones cannot easily diffuse across the capillaries to reach their target cells. they remain biologically inactive until they dissociate from plasma proteins. Most protein-bound hormones serve as reservoirs, replenishing the concentration of their free forms as they move to target receptors or lost from the circulation. Binding of hormones to plasma proteins greatly slows their clearance from the plasma  CLEARANCE OF HORMONES FROM THE BLOOD  Hormone clearance (metabolic clearance rate) from the blood is the rate of removal of the hormone from the blood.  usually expressed as number of milliliters of plasma cleared of the hormone per minute.  Metabolic clearance rate =  Hormones are “cleared” from the plasma in several ways,  (1) metabolic destruction by the tissues, (2) binding with the tissues, (3) excretion by the liver into the bile, (4) excretion by the kidneys into the urine, (5). destruction at the target by enzymatic processes after endocytosis of the cell membrane hormone-receptor complex. The receptor is usually recycled  CLEARANCE OF HORMONES FROM THE BLOOD  Water soluble hormones are usually degraded by enzymes in the blood and tissues and rapidly excreted by the kidneys and liver, thus remaining in the blood for only a short time.  Hormones that are bound to plasma proteins are cleared from the blood at much slower rates and may remain in the circulation for several hours or even days.  A decreased metabolic clearance rate may cause an excessively high concentration of the hormone in the circulating body fluids.  GENERAL HormonePRINCIPLE secretionOFoccurs in response ENDOCRINE to specific signals and FUNCTIONS is subject to feedback regulation (often negative feedback regulation).  Hormones bind to surface or intracellular receptors on the target cells causing immediate and long-term effects.  Lipid soluble hormones bind to intracellular receptors  Some hormones affect many different types of cells of the body.  growth hormone and thyroxine.  Other hormones have specific target cell. E.g., ACTH, sex hormones.  Many hormones work together to regulate body functions.  A cell can be target structure for many hormones – has  MECHANISM OF HORMONE ACTION  After reaching the target cells, hormones act on their receptors  in/on cell membrane: peptide and catecholamine  in the cytoplasm: steroid hormones  in the nucleus: thyroid hormones.  The receptor will process the message by initiating other signaling events or cellular mechanisms that result in the target cell’s response.  Number of hormones receptors vary at different times/conditions.  That is, the receptors are subjected to  A. Downregulation due to: (1) inactivation of some of their molecules; (2) inactivation of some of the intracellular signaling molecules; (3) temporary sequestration of the receptor to the inside of the cell; (4) destruction of the receptors by lysosomes after they are internalized; or (5) decreased production of the receptors. Down-regulation decreases the  B. upregulation target tissue’s responsiveness to ASSIGNMENT  State the similarities between nervous and endocrine.  State the difference between the nervous and endocrine system  Explain the methods of measuring hormone levels.  Explain the mechanisms of insulin secretion. GENERAL REGULATION OF HORMONES -ve feedback +ve feedback Shuts off the original stimulus or reduces Increases the original stimulus to push the its intensity. variable farther Values remain within a range. Values go out of range. Common in the body. Uncommon Initiated by a stimulus that disturbs the Also initiated by a stimulus such as labor body homeostasis. E.g. change in body contraction, lactation, blood clotting. temp, glucose, metab etc. THANKS THE ENDOCRINE PANCREAS THE ENDOCRINE PANCREAS  Pancreas consists of:  exocrine part – acini (~99%)  endocrine part – Islets of Langerhans.  The endocrine pancreas secretes:  2 major hormones –insulin & glucagon  Other hormones - amylin, somatostatin, and pancreatic polypeptide  ISLETS OF LANGERHANS  Irregularly shaped patches of endocrine tissue located within the pancreas.  ~1-2 million in pancreas.  Major cells are:  alpha (α), beta (β), and delta (δ) cells.  Other cells are pancreatic polypeptide (pp) cells  ISLET CELLS Alpha Beta Delta F (PP) % ~25 ~60 ~10 Secretion Glucagon Insulin & Somatosta Pancreatic Amylin (no tin polypeptid well e understoo d function) The cells are closely interrelated. Thus, they exhibit cell-to-cell communication and direct control of secretion of some of the hormones by other hormones. For example, insulin inhibits glucagon secretion, & somatostatin inhibits the secretion of both insulin & glucagon.  exocytosis MECHANISM OF INSULIN  Primary regulator is ↑SECRETION IN BETA blood glucose. CELLS  Amino- THE ENERGY ABUNDANCE acid metabolism by β cells also ↑ intracellular ATP levels & stimulate secretion.  Glucagon, glucagon-like peptide-1(GLP- Rate- 1), glucose-dependent insulinotropic limiting step peptide (gastric inhibitory peptide), & Secretory acetylcholine granules  ↑ intracellular Ca through other signaling pathways and enhance the effect of glucose.  Somatostatin & norepinephrine (by activating α-adrenergic receptors) ↓ exocytosis of insulin.  Sulfonylurea drugs (for T2DM) ↑ insulin ATP- Voltage- sensitive sensitive FACTORS AFFECTING INSULIN SECRETION Increase Insulin Secretion Decrease Insulin Secretion ↑ blood glucose Decreased blood ↑ blood free fatty acids glucose ↑ blood amino acids Fasting Gastrointestinal (GI) hormones called Somatostatin incretins (gastrin, CCK, secretin, α-Adrenergic activity glucose-dependent insulinotropic Leptin peptide, GLP-1) Glucagon, growth hormone, cortisol Parasympathetic stimulation; acetylcholine β-Adrenergic stimulation Incretins Insulin are released resistance; obesityfrom GIT to cause an “anticipatory” ↑ in blood insulin Sulfonylurea drugsin preparation for the glucose and amino (glyburide, tolbutamide) GENERAL INSULIN ACTION AT TARGET RECEPTOR  Binding to α subunits of membrane-bound receptor.  The insulin receptor: the combination of 4 subunits held together by disulfide linkages (2 α subunits & 2 β subunits).  Regulation of carbohydrate, protein and fat metabolism.  GLUT4 translocation from the intracellular environment to the cell membrane ↑ glucose uptake in insulin- sensitive tissues.  GLUT2 works in beta cells and the liver. FUNCTIONS OF INSULIN  DIABETES MELLITUS (DM)  Diabetes mellitus is a syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin.  There are two general types of diabetes mellitus:  Type 1 diabetes: insulin-dependent diabetes mellitus (IDDM), caused by lack of insulin secretion by beta cells.  Type 2 diabetes: non–insulin-dependent diabetes mellitus (NIDDM) caused by decreased sensitivity of target tissues to the metabolic effect of insulin. This reduced sensitivity to insulin is often called insulin resistance. GLANDS HYPERSECRETION UNDERSECRETION 1. ACTH Adrenal hyperplasia ( Cushing’s Secondary adrenocortical insufficiency disease if Pituitary tumour is the sources 2. GH Acromegaly (in adults) Dwarfism Gigantism (in children) 3. TSH Secondary hyperthyroidism Secondary Hypothyroidism 4. PRL Hyperprolactinemia Hypoprolactinemia 5. ADH Syndrome of inappropriate ADH Diabetes insipidus (SIADH) secretion 6. Testosterone Hyperandrogenism, weight gain Erectile dysfunction 7. Insulin Hyperinsulinemia Hypoinsulinemia, diabetes mellitus