EndocrineSystemHumanPhysiologyUnit3

EndocrineSystem

• Variousglandslocatedthroughoutthebody• Someorgansmayalsohaveendocrinefunctions• Endocrineglands/organssynthesizeandreleasehormones• Hormonestravelinplasmatotargetcells

FunctionsoftheEndocrineSystem

• Differentiationofnervousandreproductivesystemduringfetaldevelopment• Regulationofgrowthanddevelopment• Regulationofthereproductivesystem• Maintainshomeostasis• Respondstochangesfromrestingstate

MechanismsofHormoneRegulation

• Hormoneshavedifferentratesandrhythmsofsecretion

• Hormonesareregulatedbyfeedbacksystemstomaintainhomeostasis

• Receptorsforhormonesareonlyonspecificeffectorcells

• Excretionofhormonesvaryforsteroidhormonesandpeptidehormones

RegulationofHormoneSecretion

• Releaseofhormonesoccursinresponseto• A changefromrestingconditions• Maintainingaregulatedlevelofhormonesorsubstances

• Hormonereleaseisregulatedby• Chemicalfactors(glucose,calcium)• Endocrinefactors(tropichormones,HPA)• Neuralcontrols(sympatheticactivation)

HPA =Hypothalamic-PituitaryAxis

HormoneFeedbackSystems

Negativefeedbackmaintainshormoneconcentrationswithinphysiologicalranges

• Negativefeedback• Feedbacktoonelevel

• Long-loopNegativeFeedback• Feedbacktotwolevels• Hypothalamus-Pituitary-GlandAxis

Lossoffeedback

controloftenleadstopathology

NegativeFeedbackShort-LoopNegativeFeedback Long-LoopNegativeFeedback

HormoneTransportPeptide/ProteinHormones

• Circulateinfreeforms(unbound)• Shorthalflife• Degradedbycirculatingenzymes

• Examples• Insulin:t ½ =3-5minutes• Hypolthalamic hormones• Pituitaryhormones• ParathyroidHormone(PTH)

LipidSolubleHormones

• Circulateboundtocarrierortransportproteins(albumins)• Remaininbloodfromhourstodays• Examples

• Androgens• Estrogen,progesterone• Glucocorticoids• Mineralcorticoids• VitaminD• Thyroidhormone• Arachidonicacidderivatives

HormoneReceptors

• Ahormonereleasedintoplasmacirculatesthroughouttheentirebody• Onlycellswiththereceptorsforthosehormonescanrespond• Cellreceptorshave2functions• Recognizeandbindtohormonewithhighaffinity• Initiateasignaltointracellulareffectors

HormoneReceptors

• Sensitivityisrelatedtothenumberofreceptors• Plasmamembranereceptorsareconstantlybeingsynthesizedanddegraded

• Regulationasaresponse• Changesin[receptor]mayoccurwithinhours

• Physiologicalconditionsaffectreceptornumberandaffinity• pH• Temperature• Ionconcentration• Diet• Otherchemicals(drugs)

PlasmaMembraneReceptorsSignalTransduction

2nd Messenger AssociatedHormonescAMP Adrenocorticotropic Hormone(ACTH)

LuteinizingHormone(LH)HumanChorionicGonadotropin(hCG)Follicle-stimulatingHormone(FSH)ThyroidStimulatingHormone(TSH)AntidiureticHormone(ADH)ThyrotropinReleasingHormone(TRH)ParathyroidHormone(PTH)Glucagon

cGMP AtrialNatriureticPeptide(ANP)

2nd Messenger AssociatedHormones

Calcium AngiotensinIIGonadotropin-Releasing Hormone(GnRH)AntidiureticHormone(ADH)

IP3 andDAG AngiotensinIIAntidiureticHormone(ADH)

TyrosineKinaseJAK

InsulinGrowthHormone(GH)LeptinProlactin

HormoneEffects

• Bindingofhormonesttheirreceptorstrigger3typesofresponses1. Actsonpre-existingchannel-formingproteinstochangemembranepermeability2. Activatingpre-existingproteinsbya2nd messenger3. Activatinggenesresultinginproteinsynthesis

• DirectEffects• Changesincellfunctionresultfromhormonebinding• Insulin causescellularglucose/aminoaciduptake

• PermissiveEffects• Hormoneinducedchangesthatfacilitatethemaximalresponseofacell• Insulin hasapermissiveeffectonmammaryglandcells,facilitatingtheirresponsetoprolactin

HormoneExcretion

• SteroidHormoneExcretion• Excreteddirectlybythekidneys• Metabolized(conjugated)bytheliverwhichinactivatesthemandmakesthemmorewatersoluble

• PeptideHormoneExcretion• Deactivatedbyenzymesandexcretedinurineorfeces

Hypothalamic-PituitaryAxisAnteriorPituitary

• Neurosecretorycellsinthehypothalamuscommunicatewithendocrinecellsintheanteriorpituitary• Hypothalamo-pituitaryportalvessels• Endocrinecellsoftheanteriorpituitarysecretetheirhormonesintogeneralcirculation

PosteriorPituitary

• Hypothalamicneuronsextendintotheposteriorpituitary• Hypothalamohypophysial nervetract

• NeuronsoftheSupraoptic NucleusandParaventricularNucleus• Hormonesarestoredandreleasedfromtheposteriorpituitaryintogeneralcirculation

Hypothalamic-PituitaryAxis

Hypothalamo-pituitaryportalvessels

CapillariesinInfundibulum↓

Venule↓

CapillariesinAnteriorLobe↓

Venule↓

GeneralCirculation

Hypothalamohypophysial NerveTract

Hypothalamus

• Neuralinputtotheneurosecretorycellsofthehypothalamuscontroltheiractions• Neuronsfromotherpartsofthebrain• Sensoryfeedbacktothehypothalamus

• Neurosecretorycellssecretereleasingandinhibitinghormones

• Hypophysiotropic Hormones• Tropichormonescauseotherhormonestobeproduced• TropicHormonesreleasedbythehypothalamusthatcausehormonestobereleasedbytheanteriorpituitary

Hypothalamus

HypothalamusHormone TargetTissue Actions

Thyrotropin-Releasing Hormone(TRH) AnteriorPituitary (+)ThyroidstimulatingHormone(TSH)

Gonadotropin-ReleasingHormone(GnRH) AnteriorPituitary (+)FollicleStimulatingHormone(FSH)(+)LuteinizingHormone(LH)

GrowthHormoneReleasingHormone(GHRH)Somatocrinin

AnteriorPituitary (+)GrowthHormone(GH)

Somatostatin AnteriorPituitary (-)GrowthHormone(GH)(-)ThyroidStimulatingHormone(TSH)

Corticotropin-ReleasingHormone(CRH) AnteriorPituitary (+)Adrenocorticotropic Hormone (ACTH)(+)βendorphin

SubstanceP AnteriorPituitary (+)GrowthHormone (GH)(+)FollicleStimulatingHormone(FSH)(+)LuteinizingHormone(+)Prolactin(-)AdrenocorticotropicHormone(ACTH)

Prolactin-Releasing Factor(PRF) AnteriorPituitary (+)Prolactin

Dopamine(DA) AnteriorPituitary (-)Prolactin

Hypothalamus

AnteriorPituitary

• Alsocalledadenohypophysis• Chromophils arethesecretorycellsoftheanteriorpituitary• 7differentsub-types

• Secretestropichormones• Causestargetglandstosecretehormones

• Regulationoftheanteriorpituitary• Feedbackofthereleasing/inhibitinghormones• Feedbackfromtargetglandhormones• Directeffectsofneurotransmitters

Anterior Pituitary

AnteriorPituitaryHormone TargetOrgan Actions

Adrenocorticotropic Hormone(ACTH) AdrenalCortex (+)Cortisol,DHEA

MelanocyteStimulatingHormone (MSH) AnteriorPituitary (+)Secretion ofmelatonin

GrowthHormone(GH) Liver(andMuscle,Bone) (+)Insulin-Like GrowthFactor(IGF-1)

Prolactin MammaryGlands (+)production ofmilk

Thyroid-StimulatingHormone(TSH) ThyroidGland (+)ThyroidHormone(T3,T4)(+)iodideuptake

LuteinizingHormone(LH) GonadsWomen – granulosacellsMen– Leydig cells

(+) progesteroneOvulation(+)testosteroneTesticulargrowth

FollicleStimulatingHormone (FSH) GonadsWomen– granulosacellsMen– Sertoli cells

(+)estrogenFollicledevelopmentSpermatogenesis

β-Lipotropin Adipocytes Lipolysis

β-Endorphins Adipocytes(Brainopioid receptors)

Analgesia, foodandwaterintake,bodytemperatureregulation

Anterior Pituitary

PosteriorPituitary

• Alsocalledneurohypophysis• Secretes2peptidehormones• Oxytocin• AntidiureticHormone(ADH)

• Secretedfromthehypothalamus• Supraoptic nucleus• Paraventricularnucleus

Posterior Pituitary

PosteriorPituitaryHormone TargetGland Actions

Oxytocin UterinesmoothmuscleMammaryGlands

CausesuterinecontractionCausesthe“milkejection”reflex

AntidiureticHormone (ADH) Kidney tubules Controlsplasmaosmolality

Posterior Pituitary

PinealGland

• ContainsphotoreceptorcellsthatsecreteMelatonin• Synthesizedfromtryptophan• tryptophan→serotonin→melatonin

• Melatoninrelease:• Stimulatedbyexposuretodark• Inhibitedbyexposuretolight

• Melatoninregulatescircadianrhythmsandreproductivesystems

Pineal Gland

ThyroidGland

• NeuronsoftheANS terminateonbloodvesselsofthethyroid• ACh• Catecholamines

• Thyroidglandsecretes2hormones• Thyroidhormone• Calcitonin

ActionsofTSH ontheThyroid1. Immediatereleaseofstoredthyroid

hormone2. Increasediodideuptakeandoxidation3. Increaseinthyroidhormonesynthesis4. Increaseinthesynthesisandsecretionof

prostaglandinsbythethyroid5. Stimulatesthegrowthandmaintenance

ofthethyroid

Thyroid Gland

ThyroidGlandFeedback

• Regulationofthyroidhormonebylong-loopnegativefeedback• StimulusforsecretionofTRHfromthehypothalamus• Sleep• Extremecold• Exercise• Stress• Lowplasmaglucose

Thyroxine(T4)ismonitoredinplasmaforfeedback

Thyroid Gland

ThyroidHormoneSynthesis

• Follicularcellsformthyroidfollicles• ThyroidHormoneissynthesizedinsidethefollicles• Triiodothyronine(T3)• Thyroxine(T4)

• Iodideisattachedtotyrosineringsboundtothyroglobulininsidethefollicle• MIT+DIT =T3• DIT+DIT =T4

MCT:Thyroidhormonetransporter

ThyroidHormoneproduced:90%T410%T3

Thyroid Gland

ThyroidHormoneTHReceptors

• Inthetissues,T4 isconvertedtoT3 whichbindstonuclearhormonereceptors• Thyroidbetareceptor(THβ1,THβ2)• Liver,brain• Modulatescholesterolandtriglyceridelevels

• Thyroidalphareceptor(THα1)• Heart• Modulatesheartrate,contraction

Thyroid Gland

ThyroidHormoneDirectActions

• Regulatescellmetabolism• Proteinmetabolism• Triglyceridemetabolism• Glucosemetabolism

• Increasedcellularmetabolismincreases• Oxygenconsumption• Heatproduction

• Maintains• Healthymetabolicprocesses• Normalgrowthandmaturation• ActivityofNa+/K+/ATPasepumps

PermissiveActions

• Stimulatesboneresorption• Fetalneurologicdevelopment• Neurologicfunctioninginadults• Growthhormonesecretion• Skeletalmaturation• Andmore………

Thyroid Gland

ThyroidHormonePathologies

• Withinphysiologicalranges,thepermissiveeffectsaremodest• ThepermissiveeffectsofTHbecomepronouncedwhentherearehigh/lowcirculatinglevels• Hyperthyroidism• Hypothyroidism

Thyroid Gland

Calcitonin

• Parafollicular Cells(CCells)• SecreteCalcitonin• Causesserumcalciumlevelstodecrease• Inhibitsosteoclasts

• Usedtotreat• Osteoporosis• Osteoarthritis• Pagetbonedisease• Hypercalcemia• Metastaticbonecancer

Thyroid Gland

ParathyroidGland

• ProduceParathyroidHormone(PTH)• WorkswithvitaminDtoincreaseserumCalciumlevels• Concomitantdecreaseinserumphosphatelevels

• Watersolublehormone• GPCR +cAMPreceptors

• Actsonbone• Osteoclastactivity,proliferation

• Actsonkidneys• ActsonDCT toincreasecalciumreabsorption

Parathyroid Gland

Pancreas

• IsletsofLangerhanshave4secretorycelltypes• Pancreatichormonesregulatecarbohydrate,fatandproteinmetabolism• Alphacells

• Glucagon• Betacells

• Insulin• Deltacells

• Somatostatin• Fcells

• Polypeptideregulatingdigestion

Pancreas

Insulin

• Apeptidehormone• Secretionisregulatedby• Chemicalcontrol:serumglucose,aminoacids• Neuralcontrol:ANS• Hormonalcontrol:GIhormones

• Insulin(feedback)• Glucagon• Gastrin• Cholecystokinin• Secretin

ActionsofInsulin

• Facilitatestherateofglucoseandaminoaciduptake• Cellularglucoseuptakebyglucosetransporters• GLUTtransporters• Primarytransporter:GLUT4

• Cellularaminoaciduptakebyaminoacidtransporters

Pancreas

InsulinReceptors

• TyrosineKinasereceptor• Receptorsonliver,muscle,adipocytes• Receptoractivationleadstotheinsertionofglucosetransportersinthecellmembrane• Celltakesinglucose• Promotesalloftheactionsonglucose

Pancreas

InsulinActions

Actions LiverCells MuscleCells Adipocytes

Glucoseuptake Increased Increased Increased

Glycogenesis Increased Increased ------

Glycogenolysis Decreased Decreased ------

Glycolysis Increased Increased Increased

Gluconeogenesis Increased ------ ------

Other ↑ fattyacidsynthesis↓ketogenesis↓ureacycleactivity

↑aminoaciduptake↑proteinsynthesis↓proteolysis

↑fatesterification↓lipolysis↑fatstorage

Pancreas

Glucagon

• ProducedbypancreaticαcellsandcellsliningtheGItract• Stimulusforglucagonrelease• Lowserumglucose• Sympatheticstimulation• Someaminoacids• Proteinrichmeal

• Inhibitionofglucagonrelease• Highserumglucose

ActionsofGlucagon

• Liver• ↑glycogenolysis• ↑gluconeogenesis

• Adipocytes• ↑lipolysis

Pancreas

Somatostatin

• Essentialincarbohydrate,fatandproteinmetabolism• Homeostasisofingestednutrients• Regulatespancreaticalphaandbetacells

• NOTthesameashypothalamicsomatostatin

Pancreas

AdrenalGlands

RegionofAdrenalCortex %ofCortex HormonesReleased Example

ZonaGlomerulosa 15% MineralCorticoids Aldosterone*ZonaFasciculata 78% Glucocorticoids Cortisol

ZonaReticularis7%

Mineral CorticoidsAndrogensGlucocorticoids

Aldosterone*Adrenalandrogens*Estrogens*

Adrenal Glands

*Wewilldiscussthesehormoneswhenwediscussrenalandreproductivephysiology

StimulatedbyACTH

Derivedfrom

Cholesterol

AdrenalGlandsGlucocorticoids

• Glucocorticoids• Directeffectoncarbohydratemetabolism

• Glucocorticoidshavevariouseffects:• Metabolicactions• Neurologicactions• Anti-inflammatoryactions• Growth-suppressingactions

RegulationofACTH• Serumcortisollevels• Diurnalrhythms• People.Withregularsleep/wakepatterns,ACTHpeaks3-5hoursaftersleepbeginsanddeclinesthroughouttheday

• Psychologicandphysiologicstress

Adrenal Glands

AdrenalGlandsCortisol

• Mostpotentglucocorticoid• Mainsecretoryproductoftheadrenalglands• Necessaryforthemaintenanceoflifeandforprotectionfromstress• Halflifeof90minutes• Deactivatedbytheliver

ActionsofCortisol• Increasebloodglucoselevels

• Promotegluconeogenesisintheliver• Decreasinguptakeofglucosebymuscleandlymphaticcells

• Ultimateeffectonthebodyisproteinbreakdown

• Suppressionofimmunesystem• (-)boneformation• (-)ADH secretion• (+)gastricacidsecretion• Depressnervecellfunction

Adrenal Glands

AdrenalGlandsCortisol

Adrenal Glands

AdrenalGlandsCortisol– StressResponse

Adrenal Glands

OrgansThatHaveEndocrineFunction

• Someorganshaveendocrinefunctioninadditiontotheirroleaspartofanorgansystem

Organ Hormone Hormone Actions

Liver Insulin-likeGrowthFactor (IGF1)Thrombopoietin (THPO)Hepcidin

Postnatal growthPlateletproductionIron homeostasis

GastrointestinalOrgans(Entetric endocrinesystem)

MANYHormones Regulationofmotility

Kidneys ErythropoietinCalcitriol

RBCproductionVitaminDactivation

Heart AtrialNatriureticPeptide (ANP) Decreasesbloodpressure

Adipocytes Leptin Energybalance