11

Chapter 18Chapter 18The Endocrine SystemThe Endocrine System

Endocrine and nervous systems work Endocrine and nervous systems work togethertogether

Endocrine systemEndocrine system hormones released into the bloodstream hormones released into the bloodstream

travel throughout the bodytravel throughout the body results may take hours, but last longerresults may take hours, but last longer

Nervous systemNervous system certain parts release hormones into bloodcertain parts release hormones into blood rest releases neurotransmitters excite or rest releases neurotransmitters excite or

inhibit nerve, muscle & gland cellsinhibit nerve, muscle & gland cells results in milliseconds, brief duration of results in milliseconds, brief duration of

effectseffects

22

General Functions of General Functions of HormonesHormones

Help regulate:Help regulate: extracellular fluidextracellular fluid metabolismmetabolism biological clockbiological clock contraction of cardiac & contraction of cardiac &

smooth musclesmooth muscle glandular secretionglandular secretion some immune functionssome immune functions

Growth & developmentGrowth & development ReproductionReproduction

33

Endocrine Glands DefinedEndocrine Glands Defined Exocrine glandsExocrine glands

secrete products into ducts which empty into secrete products into ducts which empty into body cavities or body surfacebody cavities or body surface

sweat, oil, mucous, & digestive glandssweat, oil, mucous, & digestive glands Endocrine glandsEndocrine glands

secrete products (hormones) into bloodstreamsecrete products (hormones) into bloodstream pituitary, thyroid, parathyroid, adrenal, pinealpituitary, thyroid, parathyroid, adrenal, pineal other organs secrete hormones as a 2nd other organs secrete hormones as a 2nd

functionfunction hypothalamus, thymus, pancreas,ovaries,testes, hypothalamus, thymus, pancreas,ovaries,testes,

kidneys, stomach, liver, small intestine, skin, heart kidneys, stomach, liver, small intestine, skin, heart & placenta& placenta

44

Hormone ReceptorsHormone Receptors

Hormones only affect target cells with specific Hormones only affect target cells with specific membrane proteins called receptorsmembrane proteins called receptors

55

Role of Hormone Role of Hormone ReceptorsReceptors

Constantly being synthesized & broken Constantly being synthesized & broken downdown

A range of 2000-100,000 receptors / A range of 2000-100,000 receptors / target celltarget cell

Down-regulationDown-regulation excess hormone, produces a decrease in excess hormone, produces a decrease in

number of receptorsnumber of receptors receptors undergo endocytosis and are degradedreceptors undergo endocytosis and are degraded

decreases sensitivity of target cell to hormonedecreases sensitivity of target cell to hormone Up-regulationUp-regulation

deficiency of hormone, produces an increase deficiency of hormone, produces an increase in the number of receptorsin the number of receptors

target tissue more sensitive to the hormonetarget tissue more sensitive to the hormone

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Blocking Hormone Blocking Hormone ReceptorsReceptors

Synthetic hormones that block Synthetic hormones that block receptors for naturally occurring receptors for naturally occurring hormoneshormones RU486 (mifepristone) binds to the RU486 (mifepristone) binds to the

receptors for progesterone preventing it receptors for progesterone preventing it from maintaining the uterus in a pregnant from maintaining the uterus in a pregnant womanwoman

used to induce abortionused to induce abortion brings on menstrual cyclebrings on menstrual cycle

Hormone is prevented from interacting Hormone is prevented from interacting with its receptors and can not perform with its receptors and can not perform its normal functionsits normal functions

77

Circulating & Local HormonesCirculating & Local Hormones

Circulating hormonesCirculating hormones act on distant targetsact on distant targets travel in bloodtravel in blood

Local hormonesLocal hormones paracrines act on paracrines act on

neighboring cellsneighboring cells autocrines act on autocrines act on

same cell that same cell that secreted themsecreted them

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Lipid-soluble HormonesLipid-soluble Hormones SteroidsSteroids

lipids derived from lipids derived from cholesterol on SERcholesterol on SER

different functional different functional groups attached to groups attached to core of structure core of structure provide uniquenessprovide uniqueness

Thyroid hormonesThyroid hormones tyrosine ring plus tyrosine ring plus

attached iodines are attached iodines are lipid-solublelipid-soluble

Nitric oxide is gasNitric oxide is gas

99

Water-soluble HormonesWater-soluble Hormones Amine, peptide and Amine, peptide and

protein hormonesprotein hormones modified amino modified amino

acids or amino acids acids or amino acids put togetherput together

serotonin, serotonin, melatonin, melatonin, histamine, histamine, epinephrineepinephrine

some glycoproteinssome glycoproteins EicosanoidsEicosanoids

prostaglandins prostaglandins

1010

Hormone Transport in Hormone Transport in BloodBlood

Protein hormones circulate in free Protein hormones circulate in free form in bloodform in blood

Steroid (lipid) & thyroid hormones Steroid (lipid) & thyroid hormones must attach to transport proteins must attach to transport proteins synthesized by liversynthesized by liver

1111

General Mechanisms of Hormone General Mechanisms of Hormone ActionAction

Hormone binds to cell surface or receptor Hormone binds to cell surface or receptor inside target cellinside target cell

Cell may thenCell may then synthesize new moleculessynthesize new molecules change permeability of membranechange permeability of membrane alter rates of reactionsalter rates of reactions

Each target cell responds to hormone Each target cell responds to hormone differentlydifferently liver cells---insulin stimulates glycogen synthesisliver cells---insulin stimulates glycogen synthesis adipose---insulin stimulates triglyceride synthesisadipose---insulin stimulates triglyceride synthesis

1212

Action of Lipid-Soluble Action of Lipid-Soluble HormonesHormones

Hormone diffuses Hormone diffuses through phospholipid through phospholipid bilayer & into cell bilayer & into cell

Binds to receptor Binds to receptor turning on/off turning on/off specific genesspecific genes

New mRNA is formed New mRNA is formed & directs synthesis & directs synthesis of new proteinsof new proteins

New protein alters New protein alters cell’s activitycell’s activity

1313

Action of Water-Soluble Action of Water-Soluble HormonesHormones

Can not diffuse Can not diffuse through plasma through plasma membranemembrane

Hormone receptors Hormone receptors are integral are integral membrane proteins membrane proteins act as first messengeract as first messenger

1414

Amplification of Hormone Amplification of Hormone EffectsEffects

Single molecule of hormone binds to Single molecule of hormone binds to receptorreceptor

One molecule of epinephrine may One molecule of epinephrine may result in breakdown of millions of result in breakdown of millions of glycogen molecules into glucose glycogen molecules into glucose moleculesmolecules

1515

Hormonal InteractionsHormonal Interactions Permissive effectPermissive effect

a second hormone, strengthens the effects of the a second hormone, strengthens the effects of the firstfirst

thyroid strengthens epinephrine’s effect upon thyroid strengthens epinephrine’s effect upon lipolysislipolysis

Synergistic effectSynergistic effect two hormones acting together for greater effecttwo hormones acting together for greater effect estrogen & LH are both needed for oocyte estrogen & LH are both needed for oocyte

productionproduction Antagonistic effectsAntagonistic effects

two hormones with opposite effectstwo hormones with opposite effects insulin promotes glycogen formation & glucagon insulin promotes glycogen formation & glucagon

stimulates glycogen breakdownstimulates glycogen breakdown

1616

Control of Hormone Control of Hormone SecretionSecretion

Regulated by signals from nervous Regulated by signals from nervous system, chemical changes in the blood system, chemical changes in the blood or by other hormonesor by other hormones

Negative feedback control (most Negative feedback control (most common)common) decrease/increase in blood level is decrease/increase in blood level is

reversedreversed Positive feedback controlPositive feedback control

the change produced by the hormone the change produced by the hormone causes more hormone to be releasedcauses more hormone to be released

Disorders involve either hyposecretion Disorders involve either hyposecretion or hypersecretion of a hormoneor hypersecretion of a hormone

1717

Negative Feedback SystemsNegative Feedback Systems

Decrease in blood Decrease in blood levelslevels

Receptors in Receptors in hypothalamus & hypothalamus & thyroidthyroid

Cells activated to Cells activated to secrete more TSH secrete more TSH or more T3 & T4or more T3 & T4

Blood levels Blood levels increaseincrease

1818

Positive FeedbackPositive Feedback

Oxytocin stimulates Oxytocin stimulates uterine contractionsuterine contractions

Uterine contractions Uterine contractions stimulate oxytocin stimulate oxytocin releaserelease

1919

Hypothalamus and Pituitary Hypothalamus and Pituitary GlandGland

Both are master endocrine glands since their Both are master endocrine glands since their hormones control other endocrine glandshormones control other endocrine glands

Hypothalamus is a section of brain above Hypothalamus is a section of brain above where pituitary gland is suspended from stalkwhere pituitary gland is suspended from stalk

Hypothalamus receives input from cortex, Hypothalamus receives input from cortex, thalamus, limbic system & internal organsthalamus, limbic system & internal organs

Hypothalamus controls pituitary gland with 9 Hypothalamus controls pituitary gland with 9 different releasing & inhibiting hormonesdifferent releasing & inhibiting hormones

2020

Pea-shaped, 1/2 inch gland found in Pea-shaped, 1/2 inch gland found in sella turcica of sphenoidsella turcica of sphenoid

Anterior lobe = 75% Anterior lobe = 75% Posterior lobe = 25%Posterior lobe = 25% ends of axons of 10,000 neurons found in ends of axons of 10,000 neurons found in

hypothalamushypothalamus

Anatomy of Pituitary GlandAnatomy of Pituitary Gland

2121

Flow of Blood to Anterior Flow of Blood to Anterior PituitaryPituitary

Controlling hormones enter bloodControlling hormones enter blood Travel through portal veinsTravel through portal veins Enter anterior pituitary at capillariesEnter anterior pituitary at capillaries

2222

Human Growth HormoneHuman Growth Hormone Produced by somatotrophsProduced by somatotrophs Within target cells increases synthesis of Within target cells increases synthesis of

insulinlike growth factors that act locally insulinlike growth factors that act locally or enter bloodstreamor enter bloodstream common target cells are liver, skeletal common target cells are liver, skeletal

muscle, cartilage and bonemuscle, cartilage and bone increases cell growth & cell division by increases cell growth & cell division by

increasing their uptake of amino acids & increasing their uptake of amino acids & synthesis of proteinssynthesis of proteins

stimulate lipolysis in adipose so fatty acids stimulate lipolysis in adipose so fatty acids used for ATPused for ATP

retard use of glucose for ATP production so retard use of glucose for ATP production so blood glucose levels remain high enough to blood glucose levels remain high enough to supply brainsupply brain

2323

Regulation of hGHRegulation of hGH Low blood sugar Low blood sugar

stimulates release of stimulates release of GNRH from GNRH from hypothalamushypothalamus anterior pituitary releases anterior pituitary releases

more hGH, more glycogen more hGH, more glycogen broken down into glucose broken down into glucose by liver cellsby liver cells

High blood sugar High blood sugar stimulates release of stimulates release of GHIH from GHIH from hypothalamushypothalamus less hGH from anterior less hGH from anterior

pituitary, glycogen does pituitary, glycogen does not breakdown into not breakdown into glucoseglucose

2424

Diabetogenic Effect of Diabetogenic Effect of Human Growth HormoneHuman Growth Hormone

Excess of growth hormoneExcess of growth hormone raises blood glucose concentrationraises blood glucose concentration pancreas releases insulin continuallypancreas releases insulin continually beta-cell burnoutbeta-cell burnout

Diabetogenic effectDiabetogenic effect causes diabetes mellitis if no insulin causes diabetes mellitis if no insulin

activity can occur eventuallyactivity can occur eventually

2525

Thyroid Stimulating Hormone Thyroid Stimulating Hormone (TSH)(TSH)

Hypothalamus regulates thyrotroph Hypothalamus regulates thyrotroph cellscells

Thyrotroph cells produce TSHThyrotroph cells produce TSH TSH stimulates the synthesis & TSH stimulates the synthesis &

secretion of T3 and T4secretion of T3 and T4 Metabolic rate stimulatedMetabolic rate stimulated

2626

Follicle Stimulating Hormone Follicle Stimulating Hormone (FSH)(FSH)

Releasing hormone from Releasing hormone from hypothalamus controls hypothalamus controls gonadotrophsgonadotrophs

Gonadotrophs release Gonadotrophs release follicle stimulating hormone follicle stimulating hormone

FSH functions FSH functions initiates the formation of follicles within the initiates the formation of follicles within the

ovaryovary stimulates follicle cells to secrete estrogenstimulates follicle cells to secrete estrogen stimulates sperm production in testesstimulates sperm production in testes

2727

Luteinizing Hormone (LH)Luteinizing Hormone (LH)

Releasing hormones from hypothalamus Releasing hormones from hypothalamus stimulate gonadotrophsstimulate gonadotrophs

Gonadotrophs produce LHGonadotrophs produce LH In females, LH stimulatesIn females, LH stimulates

secretion of estrogensecretion of estrogen ovulation of 2nd oocyte from ovaryovulation of 2nd oocyte from ovary formation of corpus luteumformation of corpus luteum secretion of progesteronesecretion of progesterone

In males, stimulates interstitial cells In males, stimulates interstitial cells to secrete testosterone to secrete testosterone

2828

Prolactin (PRL)Prolactin (PRL) Hypothalamus regulates Hypothalamus regulates

lactotroph cellslactotroph cells Lactotrophs produce prolactinLactotrophs produce prolactin Under right conditions, prolactin Under right conditions, prolactin

causes milk production causes milk production Suckling reduces levels of Suckling reduces levels of

hypothalamic inhibition and hypothalamic inhibition and prolactin levels rise along with prolactin levels rise along with milk productionmilk production

Nursing ceases & milk production Nursing ceases & milk production slowsslows

2929

Adrenocorticotrophic Adrenocorticotrophic HormoneHormone

Hypothalamus Hypothalamus releasing hormones releasing hormones stimulate corticotrophsstimulate corticotrophs

Corticotrophs secrete Corticotrophs secrete ACTH & MSHACTH & MSH

ACTH stimulates cells ACTH stimulates cells of the adrenal cortex of the adrenal cortex that produce that produce glucocorticoidsglucocorticoids

3030

Melanocyte-Stimulating Melanocyte-Stimulating HormoneHormone

Secreted by corticotroph cellsSecreted by corticotroph cells Releasing hormone from Releasing hormone from

hypothalamus increases its release hypothalamus increases its release From the anterior pituitaryFrom the anterior pituitary

Function not certain in humans Function not certain in humans (increase skin pigmentation in frogs )(increase skin pigmentation in frogs )

3131

Posterior Pituitary Gland Posterior Pituitary Gland (Neurohypophysis)(Neurohypophysis)

Does not synthesize Does not synthesize hormoneshormones

Consists of axon Consists of axon terminals of terminals of hypothalamic hypothalamic neurons neurons

Neurons release two Neurons release two neurotransmitters neurotransmitters that enter capillariesthat enter capillaries antidiuretic hormoneantidiuretic hormone oxytocinoxytocin

3232

OxytocinOxytocin Two target tissues both involved in Two target tissues both involved in

neuroendocrine reflexesneuroendocrine reflexes During deliveryDuring delivery

baby’s head stretches cervixbaby’s head stretches cervix hormone release enhances hormone release enhances

uterine muscle contractionuterine muscle contraction baby & placenta are deliveredbaby & placenta are delivered

After deliveryAfter delivery suckling & hearing baby’s cry stimulates milk suckling & hearing baby’s cry stimulates milk

ejectionejection hormone causes muscle contraction & milk ejectionhormone causes muscle contraction & milk ejection

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Oxytocin during Oxytocin during Labor Labor

Stimulation of uterus by babyStimulation of uterus by baby Hormone release from Hormone release from

posterior pituitaryposterior pituitary Uterine smooth muscle Uterine smooth muscle

contracts until birth of babycontracts until birth of baby Baby pushed into cervix, Baby pushed into cervix,

increase hormone releaseincrease hormone release More muscle contraction More muscle contraction

occursoccurs When baby is born, positive When baby is born, positive

feedback ceasesfeedback ceases

3434

Antidiuretic Hormone Antidiuretic Hormone (ADH)(ADH)

Known as Known as vasopressinvasopressin

FunctionsFunctions decrease urine decrease urine

productionproduction decrease sweatingdecrease sweating increase BPincrease BP

3535

Regulation Regulation of ADHof ADH

DehydrationDehydration ADH releasedADH released

OverhydrationOverhydration ADH inhibitedADH inhibited

3636

Thyroid GlandThyroid Gland

On each side of trachea is lobe of thyroidOn each side of trachea is lobe of thyroid Weighs 1 oz & has rich blood supplyWeighs 1 oz & has rich blood supply

3737

Photomicrograph of Thyroid Photomicrograph of Thyroid GlandGland

3838

Actions of Thyroid Actions of Thyroid HormonesHormones

T3 & T4 = thyroid T3 & T4 = thyroid hormones responsible for hormones responsible for our metabolic rate, our metabolic rate, synthesis of protein, synthesis of protein, breakdown of fats, use of breakdown of fats, use of glucose for ATP glucose for ATP productionproduction

Calcitonin = responsible Calcitonin = responsible for building of bone & for building of bone & stops reabsorption of stops reabsorption of bone (lower blood levels bone (lower blood levels of Calcium)of Calcium)

3939

Control of T3 & Control of T3 & T4 SecretionT4 Secretion

Negative feedback Negative feedback systemsystem

Low blood levels of Low blood levels of hormones stimulate hormones stimulate hypothalamushypothalamus

It stimulates It stimulates pituitary to release pituitary to release TSHTSH

TSH stimulates gland TSH stimulates gland to raise blood levelsto raise blood levels

4040

Parathyroid GlandsParathyroid Glands

4 pea-sized glands found on back of thyroid 4 pea-sized glands found on back of thyroid glandgland

4141

Parathyroid HormoneParathyroid Hormone

Raise blood calcium levelsRaise blood calcium levels increase activity of osteoclastsincrease activity of osteoclasts increases reabsorption of Ca+2 by kidneyincreases reabsorption of Ca+2 by kidney promote formation of calcitriol (vitamin promote formation of calcitriol (vitamin

D3) by kidney which increases absorption D3) by kidney which increases absorption of Ca+2 and Mg+2 by intestinal tractof Ca+2 and Mg+2 by intestinal tract

Opposite function of calcitoninOpposite function of calcitonin

4242

Regulation of Calcium Blood Regulation of Calcium Blood LevelsLevels

High or low blood levels of Ca+2 stimulate the High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CTrelease of different hormones --- PTH or CT

4343

Adrenal GlandsAdrenal Glands

One on top of each kidneyOne on top of each kidney 3 x 3 x 1 cm in size and weighs 5 grams3 x 3 x 1 cm in size and weighs 5 grams Cortex produces 3 different types of hormones Cortex produces 3 different types of hormones

from 3 zones of cortexfrom 3 zones of cortex Medulla produces epinephrine & norepinephrineMedulla produces epinephrine & norepinephrine

4444

Structure of Adrenal GlandStructure of Adrenal Gland

Cortex derived from mesodermCortex derived from mesoderm Medulla derived from ectodermMedulla derived from ectoderm

4545

Regulation of AldosteroneRegulation of Aldosterone

4646

GlucocorticoidsGlucocorticoids 95% of hormonal activity is due to 95% of hormonal activity is due to

cortisolcortisol Functions = help regulate metabolism Functions = help regulate metabolism

increase rate of protein catabolism & increase rate of protein catabolism & lipolysislipolysis

conversion of amino acids to glucoseconversion of amino acids to glucose stimulate lipolysisstimulate lipolysis provide resistance to stress by making provide resistance to stress by making

nutrients available for ATP productionnutrients available for ATP production raise BP by vasoconstrictionraise BP by vasoconstriction anti-inflammatory effects reduced (skin anti-inflammatory effects reduced (skin

cream)cream) reduce release of histamine from mast cellsreduce release of histamine from mast cells decrease capillary permeabilitydecrease capillary permeability depress phagocytosisdepress phagocytosis

4747

Regulation of Regulation of GlucocorticoiGlucocorticoi

dsds Negative feedbackNegative feedback

4848

Androgens from Zona Androgens from Zona ReticularisReticularis

Small amount of male hormone Small amount of male hormone producedproduced insignificant in malesinsignificant in males may contribute to sex drive in femalesmay contribute to sex drive in females is converted to estrogen in is converted to estrogen in

postmenopausal femalespostmenopausal females

4949

Adrenal MedullaAdrenal Medulla

Chromaffin cells receive direct Chromaffin cells receive direct innervation from sympathetic nervous innervation from sympathetic nervous systemsystem develop from same tissue as postganglionic develop from same tissue as postganglionic

neuronsneurons Produce epinephrine & norepinephrineProduce epinephrine & norepinephrine Hormones are sympathomimeticHormones are sympathomimetic

effects mimic those of sympathetic NSeffects mimic those of sympathetic NS cause fight-flight behaviorcause fight-flight behavior

Acetylcholine increase hormone Acetylcholine increase hormone secretion by adrenal medullasecretion by adrenal medulla

5050

Anatomy of PancreasAnatomy of Pancreas

Organ (5 inches) consists of head, body & tailOrgan (5 inches) consists of head, body & tail Cells (99%) in acini produce digestive enzymesCells (99%) in acini produce digestive enzymes Endocrine cells in pancreatic islets produce hormonesEndocrine cells in pancreatic islets produce hormones

5151

Cell Types in the Pancreatic Cell Types in the Pancreatic IsletsIslets

Alpha cells (20%) produce Alpha cells (20%) produce glucagonglucagon

Beta cells (70%) produce insulinBeta cells (70%) produce insulin Delta cells (5%) produce Delta cells (5%) produce

somatostatinsomatostatin F cells produce pancreatic F cells produce pancreatic

polypeptidepolypeptide

5252

Regulation of Glucagon & Insulin Regulation of Glucagon & Insulin SecretionSecretion

Low blood glucose Low blood glucose stimulates release stimulates release of glucagonof glucagon

High blood glucose High blood glucose stimulates stimulates secretion of insulinsecretion of insulin

5353

Ovaries and TestesOvaries and Testes

OvariesOvaries estrogen, progesterone, relaxin & inhibinestrogen, progesterone, relaxin & inhibin regulate reproductive cycle, maintain regulate reproductive cycle, maintain

pregnancy & prepare mammary glands for pregnancy & prepare mammary glands for lactationlactation

TestesTestes produce testosteroneproduce testosterone regulate sperm production & 2nd sexual regulate sperm production & 2nd sexual

characteristicscharacteristics

5454

Pineal GlandPineal Gland

Small gland attached to 3rd ventricle of brainSmall gland attached to 3rd ventricle of brain Melatonin responsible for setting of biological Melatonin responsible for setting of biological

clockclock Jet lag & SAD treatment is bright lightJet lag & SAD treatment is bright light

5555

Effect of Light on Pineal Effect of Light on Pineal GlandGland

Melatonin secretion producing sleepiness Melatonin secretion producing sleepiness occurs during darkness due to lack of occurs during darkness due to lack of stimulation from sympathetic ganglionstimulation from sympathetic ganglion

5656

Seasonal Affective Disorder and Jet Seasonal Affective Disorder and Jet LagLag

Depression that occurs during winter Depression that occurs during winter months when day length is shortmonths when day length is short

Due to overproduction of melatoninDue to overproduction of melatonin TherapyTherapy

exposure to several hours per day of exposure to several hours per day of artificial light as bright as sunlightartificial light as bright as sunlight

speeds recovery from jet lagspeeds recovery from jet lag

5757

Thymus GlandThymus Gland

Important role in maturation of T cellsImportant role in maturation of T cells Hormones produced by gland promote Hormones produced by gland promote

the proliferation & maturation of T cellsthe proliferation & maturation of T cells thymosinthymosin thymic humoral factorthymic humoral factor thymic factorthymic factor thymopoietinthymopoietin

5858

Miscellaneous Hormones Miscellaneous Hormones EicosanoidsEicosanoids

Local hormones released by all body cellsLocal hormones released by all body cells Leukotrienes influence WBCs & inflammationLeukotrienes influence WBCs & inflammation Prostaglandins alterProstaglandins alter

smooth muscle contraction, glandular secretion, smooth muscle contraction, glandular secretion, blood flow, platelet function, nerve transmission, blood flow, platelet function, nerve transmission, metabolism etc.metabolism etc.

Ibuprofen & other nonsteroidal anti-Ibuprofen & other nonsteroidal anti-inflammatory drugs treat pain, fever & inflammatory drugs treat pain, fever & inflammation by inhibiting prostaglandin inflammation by inhibiting prostaglandin synthesissynthesis

5959

Nonsteroidal Anti-inflammatory Nonsteroidal Anti-inflammatory DrugsDrugs

Answer to how aspirin or ibuprofen works Answer to how aspirin or ibuprofen works was discovered in 1971was discovered in 1971 inhibit a key enzyme in prostaglandin synthesis inhibit a key enzyme in prostaglandin synthesis

without affecting the synthesis of leukotrieneswithout affecting the synthesis of leukotrienes Treat a variety of inflammatory disordersTreat a variety of inflammatory disorders

rheumatoid arthritisrheumatoid arthritis Usefulness of aspirin to treat fever & pain Usefulness of aspirin to treat fever & pain

implies prostaglandins are responsible for implies prostaglandins are responsible for those symptomsthose symptoms

6060

Growth FactorsGrowth Factors Substances with mitogenic qualitiesSubstances with mitogenic qualities

cause cell growth from cell divisioncause cell growth from cell division Many act locally as autocrines or paracrinesMany act locally as autocrines or paracrines Selected list of growth factors (Table 18.12)Selected list of growth factors (Table 18.12)

epidermal growth factorepidermal growth factor platelet-derived growth factorplatelet-derived growth factor fibroblast growth factorfibroblast growth factor nerve growth factornerve growth factor tumor angiogenesis factorstumor angiogenesis factors transforming growth factorstransforming growth factors

6161

Stress & General Adaptation Stress & General Adaptation SyndromeSyndrome

Stress response is set of bodily changes Stress response is set of bodily changes called general adaptation syndrome (GAS)called general adaptation syndrome (GAS)

Any stimulus that produces a stress response Any stimulus that produces a stress response is called a stressoris called a stressor

Stress resets the body to meet an emergencyStress resets the body to meet an emergency eustress is productive stress & helps us prepare eustress is productive stress & helps us prepare

for certain challengesfor certain challenges distress type levels of stress are harmfuldistress type levels of stress are harmful

lower our resistance to infectionlower our resistance to infection

6262

Alarm Reaction (Fight-or-Flight)Alarm Reaction (Fight-or-Flight)

Initiated by hypothalamic stimulation Initiated by hypothalamic stimulation of sympathetic portion of the ANS & of sympathetic portion of the ANS & adrenal medullaadrenal medulla

Dog attackDog attack increases circulationincreases circulation promotes ATP synthesispromotes ATP synthesis nonessential body functions are inhibitednonessential body functions are inhibited

digestive, urinary & reproductivedigestive, urinary & reproductive

6363

Resistance ReactionResistance Reaction Initiated by hypothalamic releasing Initiated by hypothalamic releasing

hormones (long-term reaction to stress)hormones (long-term reaction to stress) corticotropin, growth hormone & thyrotropin corticotropin, growth hormone & thyrotropin

releasing hormonesreleasing hormones ResultsResults

increased secretion of aldosterone acts to increased secretion of aldosterone acts to conserve Na+ (increases blood pressure) and conserve Na+ (increases blood pressure) and eliminate H+eliminate H+

increased secretion of cortisol so protein increased secretion of cortisol so protein catabolism is increased & other sources of catabolism is increased & other sources of glucose are foundglucose are found

increase thyroid hormone to increase increase thyroid hormone to increase metabolismmetabolism

Allow body to continue to fight a stressorAllow body to continue to fight a stressor

6464

ExhaustionExhaustion

Resources of the body have become Resources of the body have become depleteddepleted

Resistance stage can not be maintainedResistance stage can not be maintained Prolonged exposure to resistance reaction Prolonged exposure to resistance reaction

hormoneshormones wasting of musclewasting of muscle suppression of immune systemsuppression of immune system ulceration of the GI tractulceration of the GI tract failure of the pancreatic beta cellsfailure of the pancreatic beta cells

6565

Stress and DiseaseStress and Disease

Stress can lead to disease by inhibiting the Stress can lead to disease by inhibiting the immune systemimmune system hypertension, asthma, migraine, gastritis, hypertension, asthma, migraine, gastritis,

colitis, and depressioncolitis, and depression Interleukin - 1 is secreted by macrophagesInterleukin - 1 is secreted by macrophages

link between stress and immunitylink between stress and immunity stimulates production of immune substancesstimulates production of immune substances feedback control since immune substance feedback control since immune substance

suppress the formation of interleukin-1suppress the formation of interleukin-1

6666

Aging and the Endocrine Aging and the Endocrine SystemSystem

Production of human growth hormone decreasesProduction of human growth hormone decreases muscle atrophymuscle atrophy

Production of TSH increase with age to try and stimulate Production of TSH increase with age to try and stimulate thyroid thyroid decrease in metabolic rate, increase in body fat & decrease in metabolic rate, increase in body fat &

hypothyroidismhypothyroidism Thymus after puberty is replaced with adiposeThymus after puberty is replaced with adipose Adrenal glands produce less cortisol & aldosteroneAdrenal glands produce less cortisol & aldosterone Receptor sensitivity to glucose declinesReceptor sensitivity to glucose declines Ovaries no longer respond to gonadotropinsOvaries no longer respond to gonadotropins

decreased output of estrogen (osteoporosis & atherosclerosis)decreased output of estrogen (osteoporosis & atherosclerosis)

6767

Pituitary Gland DisordersPituitary Gland Disorders

Hyposecretion during childhood = pituitary Hyposecretion during childhood = pituitary dwarfism (proportional, childlike body)dwarfism (proportional, childlike body)

Hypersecretion during childhood = giantismHypersecretion during childhood = giantism very tall, normal proportionsvery tall, normal proportions

Hypersecretion as adult = acromegalyHypersecretion as adult = acromegaly growth of hands, feet, facial features & growth of hands, feet, facial features &

thickening of skinthickening of skin

6868

Thyroid Gland DisordersThyroid Gland Disorders Hyposecretion during infancy Hyposecretion during infancy

results in dwarfism & retardation results in dwarfism & retardation called cretinismcalled cretinism

Hypothyroidism in adult produces Hypothyroidism in adult produces sensitivity to cold, low body temp. sensitivity to cold, low body temp. weight gain & mental dullnessweight gain & mental dullness

Hyperthyroidism (Grave’s disease)Hyperthyroidism (Grave’s disease) weight loss, nervousness, tremor & weight loss, nervousness, tremor &

exophthalmos (edema behind eyes)exophthalmos (edema behind eyes) Goiter = enlarged thyroid (dietary)Goiter = enlarged thyroid (dietary)

6969

Cushing’s SyndromeCushing’s Syndrome

Hypersecretion of glucocorticoidsHypersecretion of glucocorticoids Redistribution of fat, spindly arms & legs due to Redistribution of fat, spindly arms & legs due to

muscle lossmuscle loss Wound healing is poor, bruise easilyWound healing is poor, bruise easily

7070

Addison’s diseaseAddison’s disease

Hypersecretion of glucocorticoidsHypersecretion of glucocorticoids hypoglycemia, muscle weakness, low hypoglycemia, muscle weakness, low

BP, dehydration due to decreased Na+ BP, dehydration due to decreased Na+ in bloodin blood

mimics skin darkening effects of MSHmimics skin darkening effects of MSH potential cardiac arrestpotential cardiac arrest

7171

Diabetes Mellitus & Diabetes Mellitus & HyperinsulinismHyperinsulinism

Diabetes mellitus marked by hyperglycemiaDiabetes mellitus marked by hyperglycemia excessive urine production (polyuria)excessive urine production (polyuria) excessive thirst (polydipsia)excessive thirst (polydipsia) excessive eating (polyphagia)excessive eating (polyphagia)

Type I----deficiency of insulin (under 20)Type I----deficiency of insulin (under 20) Type II---adult onsetType II---adult onset

drug stimulates secretion of insulin by beta cellsdrug stimulates secretion of insulin by beta cells cells may be less sensitive to hormonecells may be less sensitive to hormone