Download Ch 5 Cell Signaling and the Hormonal Responses to Exercise

ExercisePhysiology:TheoryandApplicationtoFitnessandPerformance
ByScottPowers&EdwardHowley
Ch5CellSignalingandtheHormonalResponsesto
Exercise
SummaryCreatedbyDanHechler
ClassLectureExercisePhysiologyIDr.LaurieMilliken,UMassBoston,Fall2015
Neuroendocrinology
1.Neuroendocrine
-EndocrineSystemreleaseshormones(chemicalmessengers)
-NervousSystemusesneurotransmitters
2.EndocrineGlands
-Ductlessglandsthatreleasehormonesdirectlyintotheblood
3.Exocrineglands
-Releaseproductsintoducts(sweatglands,digestiveglands)
4.Pancreas
-BothExocrine(digestiveenzymes)andEndocrine(insulinandglucagon)
Hormones
1.
-Travelinbloodtotheirspecifictargetorgans
-Receptorsarespecifictohormonessuchthatonlythecorrecthormonewillfit.
-Eachcellhas2,000to10,000specificreceptors
2.Severalclassesbasedonchemicalmakeup
-Aminoacidderivatives
-Peptides/Protein
-Steroids
BloodHormoneConcentration
Theeffectahormonehasonatissueisdeterminedbyplasmaconcentration
Determineby:
1.Rateofsecretionofhormonefromendocrinegland
-Magnitudeofinput
-Stimulatoryversusinhibitoryinput
2.Rateofmetabolismorexcretionofhormone
-Atreceptorandbytheliverandkidneys
3.Quantityoftransportprotein
-Ex.Steroidhormones
4.Changesinplasmavolume
ExampleofFactorsThatInfluenceSecretionofHormones
HormoneReceptorInteractions
1.Hormonesonlyaffecttissuewithspecificreceptors
2.Magnitudeofeffectdependenton:
-Concentrationofhormone
-Numberofreceptorsoncell
-Affinityofreceptorforhormone
3.Downregulation
-Decreaseinreceptornumberinresponsetohighconcentrationofhormone
4.Upregulation
-Increaseinreceptornumberinresponsetolowconcentrationofhormone
MechanismsofHormoneAction
1.Alteringmembranetransport
-Ex.Insulin
2.AlteringactivityofDNAtomodifyproteinsynthesis
-SteroidHormones(OnlyHormonetoDIRECTLYmodifyDNA)
3.ActivatingsecondmessengersviaGprotein
-CyclicAMP
-Ca+2
-InositolTriphosphate
-Diacylglycerol
4.TyrosineKinase
-InsulinandGrowthHormone
MechanismofSteroidHormoneAction
1.Mustbecarriedthroughcarrierprotein(duetobeingfatandnotsolubleinblood)butcan
diffuseacrosslipidbilayer(bothfat)andthenattachestoreceptorproteintobecarriedinto
thenucleustointeractwithDNA
CyclicAMP“SecondMessenger”Mechanism
1.HormoneattachestoreceptorwhichgoesthroughcellmembraneandactivatesGprotein
whichactivatesAdenlylateCyclasewhichproducesATPresultinginCyclicAMPwhichwill
activateaproteinkinasewhichcanactivatespecificcellularresponses.ThePhosphodiesterase
breaksdowntheCyclicAMPtoinhibitthisprocess.
CalciumandPhospholipaseCSecondMessengerMechanisms
InsulinReceptor
Hormones:RegulationandAction
1.Hormonesaresecretedfromendocrineglands
-Hypothalamusandpituitaryglands
-Thyroidandparathyroid
-AdrenalGlands
-Pancreas
-Testesandovaries
HypothalamusandPituitaryGland
1.Hypothalamus
-Controlssecretionsfrompituitarygland
-Releaseshormonesorfactors
2.AnteriorPituitaryGland(EndocrineConnectiontoHypothalamus)
-Adrenocorticotropichormone(ACTH)
-Follicle-stimulatinghormone(FSH)
-Luteinizinghormone(LH)
-Melanocyte-stimulatinghormone(MSH)
-Thyroid-stimulatinghormone(TSH)
-GrowthHormone(GH)
-Prolactin
3.PosteriorPituitaryGland(DirectNeuralConnectiontoHypothalamus)
-Oxytocin
-AntidiureticHormone(ADH)
HormonesoftheAnteriorPituitaryGland
InfluencesonGrowthHormoneRelease
1.Stimulatesreleaseofinsulin-likegrowthfactors(IGFs)
-IGF-1inmuscleresponsibleformusclegrowth
2.Essentialgrowthofalltissues
-AminoAciduptakeandproteinsynthesis
-Promoteslongbonegrowth(femur)
3.Sparesplasmaglucose
-Reducesuseofplasmaglucose(opposesactionofinsulin)
-Increasesgluconeogenesis(creationofnewglucosethroughnon-CHOcarbonsubstratessuch
aspyruvate,lactate,glycerol,andglycogenicaminoacids)(increasesynthesisofglucoseinliver)
-Mobilizesfattyacidsfromadiposetissues
4.Sideeffectsareacromegaly(toomuchgrowthhormone)anddiabetes
5.Respondsvianegativefeedbackloop
GrowthHormoneandPerformance
1.GHincreasesproteinsynthesisinmuscleandlongbonegrowth
-Usedtotreatchildhooddwarfismandusedbyathletesandelderly
2.Moreadverseeffectsthanbenefits
3.NoevidenceGHpromotesstrengthgains
-Proteinsynthesisiscollagen,notcontractileprotein
4.Difficulttodetectusagebyathletes
GrowthHormone
PosteriorPituitaryHormones
-PosteriorPituitary(Neurohypophysis)storeshormonesandreleasesthemasneededvia
neuralstimulation(thesehormonesareproducedinhypothalamusandsecretedtothe
neurohypophysis
-Hormones
1.Oxytocin
-Stimulatorofsmoothmuscle
-Involvedwithreleaseofbreastmilk
2.Antidiuretichormone(ADH)orvasopressin
-Stimulatedbyexercise
-Reduceswaterlossfrombodytomaintainplasmavolumeviareabsorptionofwaterfrom
kidneytubulestocapillaries
-Releasestimulatedbyhighplasmaosmolalityandlowplasmavolume(duetosweatloss
withoutwaterreplacement)
-Increasesduringexercise>60%VO2max(tomaintainplasmavolume)
ThyroidGland
1.StimulatedbyThyroidStimulatingHormone(TSH)
2.Triiodothyronine(T3)andThyroxin(T4)
-Establishmentofmetabolicrate
-Permissivehormones(Permitfulleffectofotherhormones)
3.Calcitonin
-RegulationofplasmaCa+2(minorrole)
-HighCa+2leveltriggersrelease
-Blocksreleasefrombone,stimulatesexcretionbykidneys
ParathyroidGland
1.ParathyroidHormone
-PrimaryhormoneinplasmaCa+2regulation
-StimulatesCa+2releasefrombone
-StimulatesCa+2reabsorptionbykidneys
-ConvertsVitaminD3intohormonethatincreasesCa+2absorptionfromGItract
AdrenalMedulla(LocatedOntopofKidney)
1.Secretsthecatecholamine’s
-Epinephrine(E)andNorepinephrine(NE)
-PrimarysecretionisE(80%)andispartofthe“fightorflight”response
2.Bindtoadrenergicreceptors
-Alpha
-Beta
-Effectsdependonhormoneusedandreceptortype
AdrenalCortex(OuterLayer)
1.Secretessteroidhormones
-Derivedfromcholesterol
2.Mineralocorticoids
-Aldosterone
-MaintenanceofplasmaNa+andK+
3.Glucocorticoids
-Cortisol
-Regulationofplasmaglucose
4.SexSteroids
-Androgensandestrogens
-Supportprepubescentgrowth
Aldosterone(AdrenalCortex)
1.ControlofNa+reabsorptionandK+secretion
-Maintainelectrolyte(Na+andK+)balanceinextracellularfluids
2.Regulationofbloodvolumeandbloodpressure
-Partofrenin-angiotensin-aldosteronesystem
-Vasoconstrictor(offsetslowbloodpressurewhenplasmabloodvolumedecreasesand
stimulatesaldosteronereleasewhichincreasessodiumreabsorption)
-Allthreehormonesincreaseduringexercise
3.Stimulatedby
-IncreasedK+concentration
-Decreasedplasmavolume
Cortisol(AdrenalCortex)
1.Maintenanceofplasmaglucose
-Promotesproteinbreakdownforgluconeogenesis
-StimulatesFFAmobilizationandincreaseslipolysis
-Stimulatesglucosesynthesis
-Bluntstheeffectsofinsulin(decreaseglucoseuse)
• Blocksuptakeofglucoseintocells
• PromotestheuseofFFAasfuel
-Neteffect=mobilizationoffuel
2.Stimulatedby:
-StressviaACTHPartofGeneralAdaptationSyndrome
-Exercise
3.Anti-inflammatoryagent
-Trainedrunnersareinahypercortisolismstate
-Remainselevatedpostexercise(tissuerecoveryandrepair)
Cortisol
AdiposeTissueIsanEndocrineOrgan
1.Additiontostoringtriglycerides,adiposetissuealsosecreteshormones
-Leptin
• Influencesappetitivethroughhypothalamus(decreasedleptinincreaseseating)
• Enhancesinsulinsensitivityandfattyacidoxidation
-Adiponectin
• Increasesinsulinsensitivityandfattyacidoxidation
2.Withincreasedfatmass(obesity)
-HigherLeptinlevelsandloweradiponectin
• Leptinresistance
-Leadstotype2diabetes(insulinresistance)andlow-gradeinflammation
MuscleAsAnEndocrineGland
1.Skeletalmuscleproducesmyokineswhenitcontracts
-Stimulateglucoseuptakeandfattyacidoxidation
-Promotebloodvesselgrowthinmuscle
-Promoteliverglucoseproductionandtriglyceridebreakdown
2.Interleukin6(IL-6)
• Bothpro-inflammatoryandanti-inflammatory
• IL-6producedduringexercisepromotesanti-inflammatoryeffect
• InhibitsproductionofTNF-alpha
3.Regularexercisepromotesanti-inflammatory
• Reductioninchronicinflammationandreducedriskofheartdisease,type2diabetes,
andcertaincancers
Pancreas(BothExocrineandEndocrineFunctions)
1.Secretes:
-Insulin(BetaCells)
• Promotesthestorageofglucose,aminoacids,andfats(anabolicfunctions)
• Lackofinsuliniscalleddiabetesmellitus(TypeI)
-Glucagon(AlphaCells)
• Promotesthemobilizationoffattyacidsandglucose
-Somatostatin(GammaCells)
• Controlsrateofentryofnutrientsintothecirculation
-Digestiveenzymesandbicarbonate
• Intothesmallintestine
Kidneys
1.Hormoneerythropoietinwhichregulatesredbloodcellproduction
• EPOimportantinadaptingtotrainingandaltitude
2.KidneysalsoreleasereninwhichisahormoneandenzymeinvolvedinBPcontrolandfluid
andelectrolytebalance.
TestesandOvaries
1.Testosterone
-Releasedfromtestes
-Anabolic
• Promotestissuebuilding
• Performanceenhancement
Androgenicsteroid
• Promotesmasculinecharacteristics
2.EstrogenandProgesterone
-Releasedfromovaries
-Establishandmaintainreproductivefunction
-Levelsvarythroughoutthemenstrualcycle
Table5.2Pg.107-108OverallSummaryOfHormones
HormonalControlofSubstrateMobilizationDuringExercise
1.Systemsworktomaintainnormalbloodglucoselevelsduringexercise
-Liverhas80gramsofglucosebeforeexercise
-Oxidationratesofglucosecanreach1g/mininheavyorprolongedactivity
MuscleGlycogenUtilization
1.Glycogenolysis(splittingofglycogenintoglucose)isrelatedtoexerciseintensity
-HighIntensity=greateruseofglycogenresultingindepletion
2.Plasmaepinephrinepowerfulstimulatorofglycogenolysis
-HighIntensity=increasedplasmaepinephrine
3.Evenwithepinephrineblockedviapropranololmuscleglycogenwasstillmobilized
ControlofMuscleGlycogenUtilization
1.BreakdownofmuscleglycogenisunderDualcontrol
-Epinephrine-cyclicAMP
• Viabeta-adrenergicreceptors
-Ca+2-calmodulin
• EnhancedduringexerciseduetoCa+2releasefromsarcoplasmicreticulum
2.EvidenceforroleofCa+2-calmodulininglycogenolysisfromthepropranololstudy
BloodGlucoseHomeostasisDuringExercise
PlasmaglucosemaintainedthroughFOURProcesses
1.Mobilizationofglucosefromliverglycogenstores
2.MobilizationofFFAfromadiposetissue
• Sparesbloodglucose
3.Gluconeogenesisfromaminoacids,lactate,andglycerol
4.Blockingtheentryofglucoseintocells
• ForcesuseofFFAasfuel
ControlledbyTWOTypesofHormones
1.Permissiveorslowacting
• Thyroxin,cortisol,growthhormone
2.Fasting-Acting
• Epinephrine,norepinephrine,insulin,glucagon
SlowActingHormones(Permissive)
1.ThyroidHormones(PermissiveManner)
-T3enhanceseffectofepinephrinetomobilizefreefattyacidsfromadiposetissue
-NOREALCHANGEinT3andT4duringexercise
2.Cortisol(PermissiveManner)
-StimulateFFAmobilizationfromadiposetissue
-Enhancegluconeogenesisinliver
-Decreaserateofglucoseutilizationbycells(forcingmoreFFA)
EffectsofExercise
-Decreaseduringlow-intensityexercise
-Increaseduringhighintensityexercise
• Aboveapprox.60%VO2Max
Changesincortisolmayberelatedtorepairofexercise-inducedtissuedamage
GrowthHormone(PermissiveManner)
Effects:
-Supportstheactionofcortisol
• Decreasesglucoseuptakebytissues
• IncreasesFFAmobilization
• Enhancesgluconeogenesisintheliver
ExerciseEffect
-IncreaseinplasmaGHwithincreasedintensity
-Greaterresponseintrainedrunnerscomparedtountrained
FastActingHormones
EpinephrineandNorepinephrine
1.Fastingacting
2.Maintainbloodglucoseduringexercise
• Muscleglycogenmobilization
• Increasingliverglucosemobilization
• IncreasingFFAmobilization
• Interferewithglucoseuptakeforcells
3.PlasmaEandNEINCREASEduringexercise
-Relatedtoincreasedheartrateandbloodpressureduringexercise(NEbiggerrole)
4.DecreasedplasmaEandNEfollowingtraining
DecreasedplasmaEandNEfollowingtraining;Graphbelowshowssubmaximaltrainingand
adaptationstoEandNEreleasefollowingweeksoftrainingatthatlevel.
InsulinandGlucagon(FastActingHormones)
1.Insulin
-UptakeandstorageofglucoseandFFA
-PlasmaconcentrationDECREASESduringexercise
-Decreasedinsulinresponsefollowingtraining
2.Glucagon
-MobilizationofglucoseandFFAfuels
-Plasmaconcentrationincreases
-Decreasedresponsefollowingtraining
InsulinandGlucagonsecretioninfluencedbycatecholamine’s(EandNE)
ChangesinPlasmaInsulinDURINGEXERCISE
-Decreaseduringexercise(duetoitbeinganabolichormone)
ChangesinPlasmaGlucagonDURINGEXERCISE
-Increasesduringexerciseandmoreintrainedindividuals
BloodglucoselevelsDONOTchangeduringexercisesolevelofbloodglucoseCANNOTbethe
stimulusofchangeofInsulinandGlucagonSOEpinephrineandNorepinephrinecontrolthe
releaseofGlucagonandInsulin.
SummaryofHormonalResponseDuringExercise
1.
2.
3.
4.
HormonesIncreasingGlucoseMetabolism
Glucagon(increasesglycogenolysisandgluconeogenesis)
Epinephrine(increasesglycogenolysis)
Norepinephrine(increaseglycogenolysis)
Cortisol(increasesgluconeogenesis)
1.Cortisol
2.Glucagon
3.Epinephrine
4.GrowthHormone
HormonesIncreasingFatMetabolism
SummaryofPlasmaGlucoseDuringExercise
1.Plasmaglucoseismaintainedduringexercisebyincreasingliverglycogenmobilization,using
moreplasmaFFA,increasinggluconeogenesis,decreasingglucoseuptakebytissues.
2.DecreaseinplasmainsulinandincreaseinplasmaE,NE,GH,glucagon,andcortisolduring
exercisecontrolthesemechanismstomaintainglucoseconcentration.
3.GlucoseistakenupseventotwentytimesfasterduringexercisethanatrestEVENwitha
decreaseinplasmainsulin.
4.TrainingcausesareductioninE,NE,Glucagon,andinsulinresponsestoexercise.
FreeFattyAcid&Exercise
1.FFAmobilizationdependentonhormonesensitivelipase(HSL)
2.FFAmobilizationDECREASESduringheavyexercise
-OccursinspiteofpersistinghormonalstimulationforFFAmobilization
3.Maybedueto:
-Highlevelsoflactate
• Promotesresynthesisoftriglycerides
-ElevatedH+inhibitsHSL(hormonesensitivelipase)
-Inadequatebloodflowtoadiposetissue
-InsufficientalbumintotransportFFAinplasma
EffectofLactateonFFAMobilization