Upload
others
View
7
Download
0
Embed Size (px)
Citation preview
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