ECU Lecture 10. Endocrine System PDF

MHS1102D: ENDOCRINE S YSTEM  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system.  Name the organs of the endocrine system.  Describe the relationships between the hypothalamus & pituitary gland.  List the...

MHS1102D: ENDOCRINE S YSTEM  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system.  Name the organs of the endocrine system.  Describe the relationships between the hypothalamus & pituitary gland.  List the hormones produced endocrine system, and outline the main targets and functions of each hormone.  Identify the chemical classes to which various hormones belong.  Describe how hormones stimulate their target cells.  Outline the stages of the stress response.  HOMEOSTASIS  stable internal environment  organs, tissues & cells function within certain physiological limits  when homeostatic regulation cannot compensate, disease can result  endocrine system is primary mechanism of homeostatic regulation  keeps physiological variation within normal limits compatible with survival  ignores minor variation & allows values to oscillate within a normal range  OVERVIEW OF THE ENDOCRINE SYSTEM Body has four principal mechanisms of communication between cells  Gap junctions  pores in cell membrane allow signaling molecules, nutrients & electrolytes to move from cell to cell  Neurotransmitters  released from neurons to travel across synaptic cleft to second cell  Paracrine chemicals  substances secreted into tissue fluids to affect nearby cells  Hormones  Chemical messengers that travel via bloodstream to tissues & organs  OVERVIEW OF THE ENDOCRINE SYSTEM  comprises glands, tissues & cells that secrete hormones - chemical messengers  transported by bloodstream & stimulate physiological responses in cells of another tissue or organ ▪ target organs or have receptors for specific hormones & respond to them ▪ some target cells possess enzymes that convert circulating hormones to more active form Figure 17.1  ENDOCRINE & EXOCRINE GLANDS  Exocrine glands  ducts carry secretion to an epithelial surface or mucosa of the GIT  extracellular effects (food digestion)  Endocrine glands  ductless  dense capillary networks which allow uptake of hormones into bloodstream  intracellular effects such as altering target cell metabolism  COMPARISON OF NERVOUS & ENDOCRINE SYSTEMS  both systems serve for internal communication  Speed & persistence of response  nervous: reacts quickly (ms timescale), stops quickly  endocrine: reacts slowly (seconds/days), effect may continue for days or longer  Adaptation to long-term stimuli  nervous: response declines (adapts quickly)  endocrine: response persists (adapts slowly)  Area of effect  nervous: targeted & specific (one organ)  endocrine: general, widespread effects (many organs)  COMPARISON OF NERVOUS & ENDOCRINE SYSTEMS  Several chemicals function as both hormones & neurotransmitters  norepinephrine, dopamine & ADH  Both systems can have similar effects on target cells  norepinephrine & glucagon both cause glycogen hydrolysis in liver  The two systems can regulate each other  neurotransmitters can affect glands, and hormones can affect neurons  Neuroendocrine cells share characteristics with both systems  neuron-like cells that secrete e.g. oxytocin into blood  COMMUNICATION BY NERVOUS & ENDOCRINE SYSTEMS (a) Nervous system (b) Endocrine system Figure 17.2 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system.√  Name the organs of the endocrine system.  Describe the relationships between the hypothalamus & pituitary gland.  List the hormones produced by the endocrine system and outline the main targets and functions of each hormone.  Identify the chemical classes to which various hormones belong.  Describe how hormones stimulate their target cells.  Outline the stages of the stress response.  ANATOMY OF THE ENDOCRINE SYSTEM  major anatomical structures are the hypothalamus & the pituitary gland  hypothalamus is part of diencephalon  regulates wide range of bodily functions Figure 14.2a  ANATOMY OF THE ENDOCRINE SYSTEM  pituitary gland [hypophysis] is suspended from hypothalamus by infundibulum  lies in the sella turcica of sphenoid bone  comprises two lobes of different embryological origins & separate functions  adenohypophysis (anterior pituitary)  neurohypophysis (posterior pituitary)  EMBRYONIC DEVELOPMENT OF THE PITUITARY GLAND Figure 17.3 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  PITUITARY GLAND  Adenohypophysis (anterior lobe) constitutes anterior 3/4 of pituitary gland  linked to hypothalamus by hypophyseal [vascular] portal system  primary capillaries in hypothalamus connected to secondary capillaries in adenohypophysis by portal venules  Hypothalamic hormones regulate adenohypophysis cells  hypothalamic-releasing & inhibiting hormones/factors travel in hypophyseal portal system from hypothalamus to anterior pituitary  factors promote secretion of hormones from anterior pituitary  ANATOMY OF THE PITUITARY GLAND Hypothalamic hormones Gonadotropin-releasing hormone Thyrotropin-releasing hormone Corticotropin-releasing hormone Prolactin-inhibiting hormone Growth hormone-releasing hormone Somatostatin Anterior lobe hormones Follicle-stimulating hormone Luteinizing hormone Thyroid-stimulating hormone (thyrotropin) Adrenocorticotropic hormone Prolactin Growth hormone Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 17.4b  PITUITARY GLAND ▪ Neurohypophysis (posterior lobe) constitutes posterior 1/4 of pituitary gland ▪ nerve tissue ▪ axons of nerve cell bodies in hypothalamus pass down the stalk as the hypothalamo–hypophyseal tract ▪ tract ends in the posterior lobe ▪ hypothalamic neurons secrete hormones that are stored in neurohypophysis until released into blood  POSTERIOR PITUITARY GLAND ANATOMY Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 17.4a  HISTOLOGY OF PITUITARY GLAND Figure 17.5 Copyright © McGraw-Hill Education. Permission required for reproduction or display. (a-b): © Biophoto Associates/Science Source  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system. √  Name the organs of the endocrine system. √  Describe the relationships between the hypothalamus & pituitary gland. √  List the hormones produced by the endocrine system and outline the main targets and functions of each hormone.  Identify the chemical classes to which various hormones belong.  Describe how hormones stimulate their target cells.  Outline the stages of the stress response.  HYPOTHALAMIC HORMONES/FACTORS Hypothalamic hormones Gonadotropin-releasing hormone Thyrotropin-releasing hormone Corticotropin-releasing hormone Prolactin-inhibiting hormone Growth hormone-releasing hormone Somatostatin Anterior lobe hormones Follicle-stimulating hormone Luteinizing hormone Thyroid-stimulating hormone (thyrotropin) Adrenocorticotropic hormone Prolactin Growth hormone Figure 17.4b Copyright © McGraw-Hill Education. Permission required for reproduction or display.  HYPOTHALAMIC HORMONES  oxytocin (OT) & antidiuretic hormone (ADH)  both produced by cells of hypothalamus  stored & released by posterior pituitary  not synthesized by the posterior pituitary  POSTERIOR PITUITARY HORMONES  OT & ADH released when hypothalamic neurons are stimulated  Oxytocin (OT)  stimulates labour contractions during childbirth  stimulates flow of milk during lactation  may promote emotional bonding between lactating mother & infant  promotes feelings of sexual satisfaction & bonding between partners  ADH (antidiuretic hormone)  increases water retention - reduces urine volume & prevents dehydration  also called vasopressin because it can cause vasoconstriction  ANTERIOR PITUITARY HORMONES Six principal hormones  two gonadotropin hormones target gonads  Follicle-stimulating hormone (FSH)  stimulates secretion of ovarian sex hormones, development of ovarian follicles, and sperm production  Luteinizing hormone (LH)  stimulates ovulation, stimulates corpus luteum to secrete progesterone, stimulates testes to secrete testosterone  Thyroid-stimulating hormone (TSH)  stimulates secretion of thyroid hormone  ANTERIOR PITUITARY HORMONES  Adrenocorticotropic hormone (ACTH)  stimulates adrenal cortex to secrete glucocorticoids  Prolactin (PRL)  after birth, stimulates mammary glands to synthesize milk  Growth hormone (GH)  stimulates mitosis & cellular differentiation HYPOTHALAMO–PITUITARY–TARGET ORGAN RELATIONSHIPS Figure 17.6 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  CONTROL OF PITUITARY SECRETION  Rates of secretion are not constant  regulated by hypothalamus, other brain areas & feedback from target organs  Hypothalamic & cerebral control:  brain monitors conditions & influences anterior pituitary  in times of stress, hypothalamus triggers release of ACTH  during pregnancy, hypothalamus triggers prolactin secretion  Posterior pituitary is controlled by neuroendocrine reflexes  hypothalamic osmoreceptors trigger release of ADH when they detect a rise in blood osmolarity  infant suckling triggers hypothalamic response to release oxytocin  CONTROL OF PITUITARY SECRETION Negative feedback  increased target organ hormone levels inhibit release of hypothalamic and/or pituitary hormones  E.g. thyroid hormone inhibits release of TRH by hypothalamus & TSH by anterior pituitary  Positive feedback can also occur - rarer  stretching of uterus increases OT release, causes contractions, causing more stretching of uterus, etc. until delivery  CONTROL OF PITUITARY SECRETION Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 17.7  GROWTH HORMONE  widespread effects on body tissues  cartilage, bone, muscle, and fat  bone growth, thickening & remodeling influenced  especially influential in childhood & adolescence  can peak in response to vigorous exercise Figure 17.25  induces liver to produce growth stimulants  insulin-like growth factors (IGF-I) or somatomedins (IGF-II)  stimulate target cells in diverse tissues  IGF-I prolongs the action of GH Copyright © McGraw-Hill Education. Permission required for reproduction or display.  GROWTH HORMONE  Induces liver to produce growth stimulants:  protein synthesis increases: increases amino acid uptake into cells; suppresses protein catabolism  lipid metabolism increases: stimulates adipocytes to catabolize fats (protein- sparing effect)  carbohydrate metabolism: glucose-sparing effect, mobilizing fatty acids reduces dependence on glucose, freeing more for the brain; stimulates glucose secretion by liver  electrolyte balance: promotes Na+ , K + , and Cl− retention by kidneys, enhances Ca2+ absorption in intestine; electrolytes available to growing tissues  THE PINEAL GLAND  attached to roof of third ventricle beneath posterior end of corpus callosum  after age 7, it undergoes involution (shrinkage) - reduced 75% by end of puberty  may synchronize physiological function with 24-hour circadian rhythms  synthesises melatonin from serotonin during the night  fluctuates seasonally with changes in day length  regulates onset of puberty  THE THYMUS  role in endocrine, lymphatic, & immune systems  bilobed gland in mediastinum above heart  undergoes involution after puberty  site of maturation of T-cells important in immune defense  secretes hormones that stimulate development of other lymphatic organs & activity of T lymphocytes Figure 17.8  ANATOMY OF THE THYROID GLAND  largest gland that is purely endocrine  two lobes & an isthmus below the larynx  dark reddish brown color - rich blood supply Figure 17.26 Goiter: pathological enlargement of thyroid gland ▪ endemic goiter (geographic locality) ▪ dietary iodine deficiency, no TH, no feedback, increased TSH - hypertrophy Figure 17.9a Copyright © McGraw-Hill Education. Permission required for reproduction or display.  THYROID GLAND Thyroid follicles - sacs comprising most of thyroid ▪ contain protein-rich colloid ▪ secretes thyroxine (T4 ) & triiodothyronine (T3 ) Increases metabolic rate ▪ O2 consumption ▪ heat production (calorigenic effect) ▪ appetite, ▪ growth hormone secretion ▪ alertness, reflex speed Parafollicular (C or clear) cells Figure 17.9b ▪ secrete calcitonin with rising blood Ca+ ▪ stimulates osteoblast activity & bone formation in children b: © Biophoto Associates/Science Source Copyright © McGraw-Hill Education. Permission required for reproduction or display.  THE PARATHYROID GLANDS  usually four glands, partially embedded in posterior surface of thyroid gland  secrete parathyroid hormone (PTH)  increases blood Ca2+ levels  promotes synthesis of calcitriol  increases absorption of Ca+  decreases urinary excretion  increases bone resorption Figure 17.10  THE ADRENAL GLANDS  located on upper pole of kidney  two regions  adrenal medulla - inner core, 10% to 20% of gland  cortex surrounds medulla & secretes several corticosteroids (hormones) from three layers of glandular tissue  THE ADRENAL MEDULLA  acts as endocrine gland & a ganglion of sympathetic nervous system  innervated by sympathetic preganglionic fibers  modified sympathetic postganglionic neurons called chromaffin cells  releases epinephrine & norepinephrine directly into the bloodstream  increase alertness & prepare body for physical activity  mobilize high-energy fuels, lactate, fatty acids, and glucose  epinephrine inhibits insulin secretion - glucose-sparing effect  muscles use fatty acids, saving glucose for brain  increase BP, heart rate, blood flow to muscles, pulmonary airflow, and metabolic rate  decrease digestion & urine production  THE ADRENAL GLANDS b: © Victor Eroschenko Figure 17.11 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  THE ADRENAL CORTEX Zona glomerulosa (thin, outer layer)  cells are arranged in rounded clusters  secretes mineralocorticoids - regulate electrolyte balance  Aldosterone stimulates Na+ retention & K + excretion Zona fasciculata (thick, middle layer)  cells arranged in fascicles separated by capillaries  secretes glucocorticoids & androgens Zona reticularis (narrow, inner layer)  cells in branching network  secretes glucocorticoids and sex steroids  THE ADRENAL CORTEX  Glucocorticoids [ACTH]  regulate metabolism of glucose and other fuels  cortisol & corticosterone stimulate fat & protein catabolism, gluconeogenesis (glucose from amino acids & fatty acids) & release of fatty acids & glucose into blood  help body adapt to stress & repair tissues  anti-inflammatory effect becomes immune suppression with long-term use  Cushing syndrome - excess cortisol secretion  hyperglycemia, hypertension, weakness, oedema  rapid muscle & bone loss due to protein catabolism  abnormal fat deposition, moon face  THE ADRENAL CORTEX  sex steroids or androgens: set libido; large role in prenatal male development  estradiol: small quantity from adrenals, but this becomes important after menopause for sustaining adult bone mass Adrenogenital syndrome (AGS) ▪ adrenal androgen hypersecretion ▪ enlargement of external sexual organs in children ▪ early onset of puberty ▪ newborn girls exhibit masculinised genitalia ▪ masculinising effects on women ▪ increased body hair, deeper voice https://www.slideshare.net/MuhammadSGhauri/cut-signs-androgenization  THE PANCREAS  A or alpha (α) cells of pancreatic islets secrete glucagon  released between meals when blood glucose concentration is falling  in liver, stimulates gluconeogenesis & release of glucose into circulation, raising blood glucose level  in adipose tissue, stimulates fat catabolism & release of free fatty acids  glucagon also released to rising amino acid levels in blood, promotes amino acid absorption & provides cells with raw material for gluconeogenesis Figure 17.12  THE PANCREATIC ISLETS  Insulin secreted by B or beta (β) cells  secreted during & after meal when glucose & amino acid blood levels are rising  stimulates cells to absorb these nutrients & store or metabolize them, lowering blood glucose levels  promotes synthesis glycogen, fat & protein  suppresses use of already-stored fuels  brain, liver, kidneys & RBCs absorb glucose without insulin, but other tissues require insulin  insufficiency or inaction is cause of diabetes mellitus  THE PANCREATIC ISLETS  Somatostatin secreted by D or delta (δ) cells  partially suppresses secretion of glucagon and insulin  inhibits nutrient digestion & absorption which prolongs absorption of nutrients  hyperglycemic hormones raise blood glucose concentration (includes hormones from other glands)  glucagon, growth hormone, epinephrine, norepinephrine, cortisol, and corticosterone  hypoglycemic hormones lower blood glucose  ENDOCRINE FUNCTIONS OF OTHER ORGANS  Skin  keratinocytes convert a cholesterol-like steroid into cholecalciferol using UV from sun  Liver - involved in the production of at least five hormones  converts cholecalciferol into calcidiol  secretes angiotensinogen (a prohormone)  precursor of angiotensin II (a regulator of blood pressure)  secretes 15% of erythropoietin (stimulates bone marrow)  source of IGF-I that controls action of growth hormone  hepcidin: promotes intestinal absorption of iron  ENDOCRINE FUNCTIONS OF OTHER ORGANS  Kidneys - play role in production of three hormones  convert calcidiol to calcitriol, the active form of vitamin D  increases Ca2+ absorption by intestine & inhibits loss in the urine  secrete renin that converts angiotensinogen to angiotensin I  Angiotensin II created by converting enzyme in lungs  constricts blood vessels & raises blood pressure  produces 85% of erythropoietin  stimulates bone marrow to produce RBCs  ENDOCRINE FUNCTIONS OF OTHER ORGANS  Heart  natriuretic peptides in response to increase in blood pressure  Stomach & small intestine secrete numerous enteric hormones secreted by enteroendocrine cells  coordinate digestive motility & glandular secretion  cholecystokinin, gastrin, ghrelin  ENDOCRINE FUNCTIONS OF OTHER ORGANS  Adipose tissue secretes leptin - slows appetite  Osseous tissue - osteocalcin secreted by osteoblasts  increases number of pancreatic beta cells, pancreatic output of insulin, and insulin sensitivity of body tissues  inhibits weight gain & onset of type 2 diabetes mellitus  Placenta  secretes estrogen, progesterone  regulate pregnancy, stimulate development of fetus and mammary glands  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system. √  Name the organs of the endocrine system. √  Describe the relationships between the hypothalamus & pituitary gland. √  List the hormones produced by the endocrine system and outline the main targets and functions of each hormone. √  Identify the chemical classes to which various hormones belong.  Describe how hormones stimulate their target cells.  Outline the stages of the stress response.  HORMONE CHEMISTRY  Hormones are derived from macromolecules Three chemical classes: steroids, monoamines, and peptides  Steroids  derived from cholesterol  sex steroids (e.g. oestrogen) from gonads & corticosteroids (e.g. cortisol) from adrenal glands  Monoamines (biogenic amines)  made from amino acids  catecholamines (dopamine, epinephrine, norepinephrine), melatonin, thyroid hormone  HORMONE CHEMISTRY Peptides & glycoproteins  created from chains of amino acids  pituitary hormones & releasing & inhibiting hormones from hypothalamus  insulin - large peptide hormone (c) Peptides Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 17.14c  HORMONE SECRETION  not secreted at steady rates - levels fluctuate throughout the day  some are secreted on daily (circadian) rhythm  some on a monthly rhythm (female ovarian cycle)  others under the influence of stimuli that signify a need for them  Neural stimuli  Hormonal stimuli  Humoral stimuli  HORMONE SECRETION  Neural stimuli  nerve fibers supply some endocrine glands & elicit release of hormones  SNS stimulates adrenal medulla to secrete epinephrine & norepinephrine in situations of stress  in childbirth, nerve signals originate from stretch receptors in uterus, travel up spinal cord & brainstem to hypothalamus - stimulate release of oxytocin  Hormonal stimuli  hormones from hypothalamus regulate secretion by anterior pituitary gland  pituitary hormones stimulate other endocrine glands to release hormones  HORMONE SECRETION  Humoral stimuli  refers to blood-borne stimuli  rising blood glucose concentration stimulates release of insulin  low blood osmolarity stimulates secretion of aldosterone  low blood calcium level stimulates secretion of parathyroid hormone  HORMONE SECRETION  peptide hormones & catecholamines are stored in secretory vesicles of endocrine cells until needed  released by exocytosis when cell receives a stimulus  steroid hormones are released as they are synthesized by diffusion through cell surface  stimuli such as FSH & ACTH can increase synthesis & release of a steroid hormone by several-fold within hours  Thyroid hormone (TH) also diffuses freely through plasma membranes  accumulates in extracellular spaces of gland waiting a stimulus  TSH causes secretion  PLASMA MEMBRANE RECEPTORS  Non-lipid soluble hormones (first messenger) cannot directly influence cell activity  need a messenger inside the cell (second messenger)  second messenger changes the rates of metabolic reactions  Second messengers:  Cyclic AMP (cAMP)  Cyclic GMP (cGMP)  Ca+ ions  PLASMA MEMBRANE RECEPTORS  G protein & cyclic-AMP (a derivative of ATP)  many G proteins achieve effects by changing concentration of secondary messenger [cyclic-AMP]  results in increased cAMP levels - accelerates metabolic activity within the cell  G proteins can  open Ca+ ion channels  release Ca+ ion stores  80% of prescription drugs target G protein-coupled receptors  INTRACELLULAR RECEPTORS  steroid hormones diffuse across lipid part of plasma membrane  bind to receptors in cytoplasm or nucleus  hormone-receptor complexes then bind to DNA - activate or deactivate genes  change DNA transcription in nucleus & thus translation & protein synthesis  INTRACELLULAR RECEPTORS Thyroid hormone  transported across membrane  binds to receptors in nucleus & activate genes  binds to receptors on mitochondria & accelerates ATP production  this influences metabolic rate  HORMONE TRANSPORT  Most monoamines & peptides are hydrophilic  mix easily with blood plasma  Steroids & thyroid hormone are hydrophobic  bind to transport proteins (albumins & globulins synthesized by the liver)  bound hormones have longer half-life  protected from liver enzymes & kidney filtration  only unbound hormone leaves capillaries to reach target cell  transport proteins protect circulating hormones from digestion by enzymes in plasma & liver, and from being filtered out of the blood by the kidneys  HORMONE RECEPTORS & MODE OF ACTION  hormones stimulate only those cells that have receptors for them  receptors are protein or glycoprotein molecules  on plasma membrane, in the cytoplasm, or in the nucleus  receptors ‘turn on’ metabolic pathways when hormone binds to them  each target cell has several thousand receptors for a given hormone  Receptor–hormone interactions exhibit specificity & saturation  specific receptor for each hormone  saturated when all receptor molecules are occupied by hormone molecules  HORMONE RECEPTORS & MODE OF ACTION  Peptide hormones  cannot penetrate target cell  bind to surface receptors & activate intracellular processes through second messengers  Steroid hormones  penetrate plasma membrane & bind to internal receptors (usually in nucleus)  influence expression of genes of target cell  take several hours to days to show effect due to lag for protein synthesis  HORMONE RECEPTORS & MODE OF ACTION Figure 17.18 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  PEPTIDES & CATECHOLAMINES 1) Hormone-receptor binding activates a G protein. 2) G protein activates adenylate cyclase. 3) Adenylate cyclase produces cAMP. 4) cAMP activates protein kinases. 5) Protein kinases phosphorylate enzymes. This activates some enzymes & deactivates others. 6) Activated enzymes catalyze metabolic reactions with a wide range of possible effects on the cell. Figure 17.19 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  PEPTIDES & CATECHOLAMINES Various metabolic effects Hormones Smooth muscle contraction ADH Protein synthesis TRH Secretion OT Mitosis LHRH etc. Catecholamines Figure 17.20 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  PARACRINE SIGNALING  Paracrine - chemical messengers that diffuse short distances & stimulate nearby cells – local effects  Histamine  from mast cells in connective tissue - causes relaxation of blood vessels  Nitric oxide  from endothelium of blood vessels - causes vasodilation  Catecholamines  diffuse from adrenal medulla to cortex  Autocrines - chemical messengers that stimulate same cell that secreted them  single chemical can act as a hormone, paracrine, or even neurotransmitter in different locations  MODULATION OF TARGET-CELL SENSITIVITY  target-cell sensitivity adjusted by changing number of receptors  up-regulation: number of receptors increased  sensitivity is increased Low receptor density Increased receptor density Stronger response Weak response Increased sensitivity (a) Up-regulation  down-regulation reduces number of receptors  cell less sensitive to hormone  occurs with long-term exposure to high hormone concentrations High receptor density Reduced receptor density Diminished response Strong response Reduced sensitivity (b) Down-regulation Copyright © McGraw-Hill Education. Permission required for reproduction or display. Figure 17.22  HORMONE INTERACTIONS  most cells sensitive to more than one hormone & exhibit interactive effects  Synergistic effects  multiple hormones act together for greater effect  synergism between FSH & testosterone on sperm production  Permissive effects  hormone enhances target organ response to a second later hormone  oestrogen prepares uterus for action of progesterone  Antagonistic effects  hormone opposes the action of another  insulin lowers blood glucose & glycogen raises it ANTAGONISTIC EFFECTS OF INSULIN & GLUCAGON ON LIVER Figure 17.23 Copyright © McGraw-Hill Education. Permission required for reproduction or display.  HORMONE CLEARANCE  hormone signals must be turned off when they have served their purpose  most hormones are taken up & degraded by liver & kidney  excreted in bile or urine  Metabolic clearance rate (MCR)  rate of hormone removal from the blood  half-life: time required to clear 50% of hormone from the blood  the faster the MCF, the shorter the half-life  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system. √  Name the organs of the endocrine system. √  Describe the relationships between the hypothalamus & pituitary gland. √  List the hormones produced by the endocrine system and outline the main targets and functions of each hormone. √  Identify the chemical classes to which various hormones belong. √  Describe how hormones stimulate their target cells. √  Outline the stages of the stress response.  STRESS & ADAPTATION Stress - situation that disturbs homeostasis  can threaten physical or emotional well-being  injury, surgery, infection, intense exercise, pain, grief, depression, anger, etc. General adaptation syndrome (GAS)  consistent way the body reacts to stress  typically involves elevated levels of epinephrine & glucocorticoids (especially cortisol)  Occurs in three stages Alarm reaction Stage of resistance Stage of exhaustion  THE ALARM REACTION  Initial response  mediated by norepinephrine from SNS & epinephrine from adrenal medulla  prepares body for fight or flight  stored glycogen is consumed  increases aldosterone & angiotensin levels  Angiotensin helps raise blood pressure  Aldosterone promotes Na+ & H2O conservation  THE STAGE OF RESISTANCE  after a few hours, glycogen reserves gone, but brain still needs glucose  provide alternate fuels for metabolism  stage dominated by cortisol  hypothalamus secretes corticotropin-releasing hormone (CRH)  pituitary secretes ACTH  stimulates the adrenal cortex to secrete cortisol and other glucocorticoids  promotes breakdown of fat & protein into glycerol, fatty acids, and amino acids for gluconeogenesis  THE STAGE OF RESISTANCE Cortisol has glucose-sparing effect  inhibits protein synthesis leaving free amino acids for gluconeogenesis  Adverse effects of excessive cortisol: depresses immune function increases susceptibility to infection and ulcers lymphoid tissues atrophy, antibody levels drop & wounds heal poorly  THE STAGE OF EXHAUSTION  if stress continues over months & fat reserves are gone, homeostasis is overwhelmed  often marked by rapid decline and death  protein breakdown & muscle wasting  loss of glucose homeostasis because adrenal cortex stops producing glucocorticoids  Aldosterone promotes H2O retention & hypertension  conserves Na+ & promotes elimination of K + and H +  hypokalemia & alkalosis can result in death  death can be due to heart & kidney infection or overwhelming infection  ANTI-INFLAMMATORY DRUGS  Cortisol & corticosterone  Steroidal anti-inflammatory drugs (SAIDs)  inhibit inflammation by blocking release of arachidonic acid from plasma membrane & inhibit synthesis of eicosanoids  Disadvantage - produce symptoms of Cushing syndrome  Aspirin, ibuprofen & celecoxib (Celebrex)  Nonsteroidal anti-inflammatory drugs (NSAIDs)  useful in treatment of fever & thrombosis  inhibit prostaglandin & thromboxane synthesis  LEARNING OUTCOMES By the end of this lecture you should be able to:  Define hormone and endocrine system. √  Name the organs of the endocrine system. √  Describe the relationships between the hypothalamus & pituitary gland. √  List the hormones produced by the endocrine system and outline the main targets and functions of each hormone. √  Identify the chemical classes to which various hormones belong. √  Describe how hormones stimulate their target cells. √  Outline the stages of the stress response. √  NEXT LECTURE REPRODUCTIVE SYSTEM 1