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Hypertrophy/Hyperplasia:Stimuli Damage
Carlson,B.M.theregenerationofskeletalmuscleAmJAnat 137:119150,1973
EFFECTOFTRAININGONMUSCLEFIBERSIZE
Maybemorepronouncedwithhighpowermovements
MUSCLESTRUCTURALADAPTATIONSTORT
HYPERTROPHY(INCREASEDCSA)
PROTEINREMODELING SYNTHESISAND/OR DEGRADATION FIBERTYPESPECIFICRESPONSE TypeI:synthesisanddegradation TypeIIsynthesisanddegradation TypeIIfiberstendtorespondatafasterratethanTypeI
Hakkinenetal.JGerontolABiolSciMedSci53(6):B41523,1998 Deschenes,M.R.etal.Enduranceandresistanceexerciseinduces musclefibretype specificrespsonsesinandrogenbindingcapacity.J.SteroidBiochem BiochemMol.Bio 50:175179,1994
TASKSPECIFICHYPERTROPHY
RegionalHypertrophy:
Abe,T.etal.BrJSportsMed37543545,2003.
BasicMechanisms
IncreasedMuscle Tension Stretch MechanicalStress Initialdamage Zdisk streamingandmyofibrillar disruption plasmamembrane disruption
myostatin()
TissueRemodeling
MechanicalStimuliLeadingtoTissueRemodeling
Initiation
ExerciseStimulus
Alteredenzyme/isozyme concentrations
AlteredGeneExpression Transcriptionfactors
Increased translationalactivity Proteinsynthesis
AMPKSignaling
Endurance Exercise, Insulin, TZDs, Metformin Volume Effects, Hypoxia, AICAR, IRS1 [AMP]:[ATP] PI-3 Kinase LKB1 MTORC1 ( ) Muscle Contraction [Ca2+]
LowMuscle Glycogen
AMPK
Fatty Acid Oxidation Mitochondrial Biogenesis
mTORSignaling
Resistance exercise, growth factors, amino acids, rapamycin
IRS1 PI3K PIP3 PDK1
Akt
TSC2
Rheb
mTORC1
Raptor
Deptor mLST8
PRAS40
mTORC1
4E-BP1 eIF4E Cap-dependent translocation mRNA Biogenesis Translation elongation S6K1
Strongrelationbetween mTORC1activation,increased FFMandstrength: TerzisG.etal.resistance exerciseinducedincreasein musclemasscorrelateswith p70S6 kinasephosphoylation inhumansubjects.EuJAppl Physiol102:145152,2007. After14wksofresistance traininginyoungmales(n=6) thephosphorylation activation)ofp70S6k was stronglycorrelatedwith increasedFFMwb (r=0.89), FFMleg(r=0.81),1RMsquat (r=0.84)andTypeIIXsec area(r=0.82). Phosphorylationof p70S6K indicates mTORC1activation
Exercise=simultaneousactivationofdifferentICSpathways
() myostatin
Myostatin (growthdifferentiationfactor8:GDF8):secretedasaTGFbeta proteinfamilymemberthatinhibitsmuscledifferentiationandgrowth. Myostatin:producedprimarilyinskeletalmusclecells,circulatesinthe bloodandactsonmuscletissuebybindingacellboundreceptor(activin typeIIreceptor)andinhibitingtheactionofspecificgrowthfactorsand mitogenssuchasIGF1 Animalslackingmyostatin(oranimalstreatedwithsubstancessuchas follistatinthatblockthebindingofmyostatintoitsreceptor) have substantiallylargermuscles.
Photographsofchildat7 months,6days
a. b. c. d.
Muscle Development
(-)
growth
(-)
Androgen s
Myostatin
Moststudies(notall):ResistanceExercise/Trainingappears to downregulatemyostatinexpression
Exercise
Kvorning,T.etal.SuppressionoftestosteronedoesnotbluntmRNA mRNAexpressionofmyoD, myogenin,IGF,myostatinorandrogenreceptorpoststrengthtraining traininginhumans.JPhysiol578(pt 2):579593,2006
Training
Jeongsu,K.etal.EndocrinologyandMetabolism 288:E1110E1119,2005 Walkeretal.MedicineandScienceinSportsandExercise36:787793,2004 Rothetal.ExperimentalBiologyandMedicine 228:706709,2003 SaremiA.etal.MolecularCellEndocrinology.2010Apr12;317(12):2530,2009(mayinteractwithcreatine) Hulmii,J.J.ResistanceexercisewithwheyproteiningestionaffectsmTORsignaling signalingpathwayandmyostatinin men. JApplPhysiol.106(5):17209,2009.
EndocrineInfluences AcutevsChronic
DirectEffectsofHormones:
Androgens&Estrogens receptorsforbothinskeletalmyofibers possible directeffectstoincreasemuscleproteinsynthesis Androgenshavebeenassociatedwithincreasedsatellitecellnumber numberandincorporation
Insulin Myofibers havemoreinsulinreceptorsthanIGF1receptorsthusinsulinisnecessaryformyofiberhypertrophy thishypertrophyisnecessarytostoreproteininmuscle Restingmuscle needsinsulintoincreaseinsize(i.e.increasenutrientuptake uptakeforstorageandproductionof contractileproteinsecretion);thusfollowingameal,wheninsulin insulinissecreted,excessnutrientscanbestoredin muscle.Ifinsulinislow,musclesatrophyandproteinstoresare aremobilized. Contractingmuscle doesnotneedinsulinforglucoseuptake;thusnutrientsinthe circulationcanentermuscleto supplyenergyforcontractionwithouteatingamealandgettingthesubsequentriseincirculatinginsulin GrowthHormone(GH,somatotropin) Nodirecteffects.ThereisnoevidenceofGHreceptorsonskeletal skeletalmuscle. ThyroidHormones thyroidhormonesrequiredforcontrolofmyofibermaturation :duringdevelopmenttheyincreasemyofibersize andaffectanaerobicmetabolism Glucocorticoids excessiscatabolicinmuscle(myofibers) excessdecreasesproteinsynthesis excessincreasesproteindegradation
AcuteEndocrineinfluences:
Hypothesis: postexercise (lasting 10 40 min) endocrine responses influence hypertrophy (recurrent mechanical stimuli + increased hormone concentrations such as hGH and T result in accentuated hypertrophy hypertrophy responsethatsummatesovertime) large muscle mass exercise elevates hormones to a greater extent than smallmusclemassexercise
Evidence:onlyfourstudiesfound:
Hansen S., Kvorning T., Kjaer M., Sjogaard G. The effect of shortterm strength training on human skeletal muscle: the importance of physiologically elevated hormone levels. Scand J Med Sci Sports 11: 347354, 2001 incorporation of leg work (HH)priortoarmwork(LH)enhancedarmstrengthgains(hypertrophynotdirectlymeasured) Ahtiainen J.P et al. Muscle hypertrophy, hormonal adaptations and strength development during strength training in strength trained and untrained men. Eur J Appl Physiol 89:55563, 2003. Mean acute responses across 21 weeks of training correlated withisometricstrengthandCSA(however,basalandmeanacutewerestronglycorrelated) Beaven CM. et al. Significant strength gains observed in Rugby players after specific resistance exercise protocols based on individual salivary testosterone responses, JSCR 22: 419425, 2008. Longterm effect assumption was that responses made difference nodirectevidence nomeasureofLBM/CSAalterations changesinstrengthwerenotlarge problems? Spiering,B.A.Kraemer,,W.J.,Vingren, J.L., Ratamess, N.A., Anderson, J.M., Armstrong,L.E., Nindl, B.C., Volek, J.S., HkkinenH. and Maresh, C.M.. Elevated endogenous testosterone concentrations potentiate muscle androgen receptor responses to resistance exercise . J Steroid Biochemi Mol Biol 114: 195199, 2009 . incorporation of leg work prior to arm work enhanced androgenreceptorcontent(hypertrophynotdirectlymeasured)
AcuteEndocrineinfluences:
Hypothesis: postexercise endocrine responses influence hypertrophy (recurrent mechanical stimuli + increased hormone concentrations such as hGH hGH and T result in accentuatedhypertrophyresponsethatsummatesovertime) Evidenceagainst:
1.Hypophysectimized, 1.Hypophysectimized, castrated animals can still show considerable hypertrophy when trained however adding T or T +GH chronicallydoesincreaseeffect. 2.Short 2.Shortterm higher intensity aerobic exercise can result in marked increases increases in anabolic hormones however, aerobic exercise resultsinlittleornohypertrophy 3.Increased 3.Increasedhormone(especiallyT)concentrationscanbehigheras aresultofcircadianrhythmsthanpostexercisevalues.(Training timemayinfluencethis) McMillan,J.etal.20hourphysiologicalresponsestoasingleweighttrainingsessionJStrengthCondRes 7:921,1993 Bird, S.P. and Tarpening K.M. Influence of circadian time structure structure on acute responses to a single bout of heavy resistanceexerciseinweighttrainedmen.ChronobiologyInternational21:131146,2004 4. Women have approximately 10 % of the testosterone concentration of men but show the same relative relative hypertrophycomparedwithmen. Cureton, K. J., Collins M.A. HILL D.W. and McElhannon F. M. . Muscle hypertrophy in men and women. Med. Sci. Sports.Exerc,Vol.20,No.4,pp.338344,1988. O'Hagan F.T., Sale D.G., MacDougall .JD., Garner S.H. Response to resistance training in young women and men. Int J SportsMed.16:31421,1995.
AcuteEndocrineinfluences:
Hypothesis: postexercise endocrine responses influence hypertrophy (recurrent mechanical mechanical stimuli + increased hormone concentrations such as hGH and T result result in accentuated hypertrophyresponsethatsummatesovertime) Evidenceagainst: 3.No 3.No correlation or evidence of hypertrophy (or strength) enhancement enhancement as a result of acute hormoneresponses:
Wilkinson, S.B. Hypertrophy with unilateral resistance exercise occurs without increases in endogenous anabolic hormone concentrationEur J ApplPhysiol 98:546555, 2006.Hypertrophyoccurredonly in thetrained leg and occurred independently independently of hormone elevation Kvorning, T. et al. Suppression of testosterone does not blunt mRNA mRNA expression of myoD, myogenin, IGF, myostatin or androgen receptor post strength training in humans. J Physiol 578(pt 2): 579593, 2006 . treatment with goserelin causes lower T placeboshowed increasedpostex T, goserelin group showed decreased T responses; no differences differences between groups in mRNA expression, myoD,myogenin,IGF,myostatinorandrogenreceptorpoststrength strengthtraininginhumans West, D.W., et al. Resistance exerciseinduced increases in putative anabolic hormones do not enhance muscle muscle protein synthesisor intracellular signalingin youngmen. J Physiol. 587(pt2): 52395247, 2009. markers of protein synthesis and markers of mTOR werenotdifferentbetweenarmonly(LH)andarm+leg(HH)resistance resistanceexercise. West, D.W., et al. Elevations in ostensibly anabolic hormones with with resistance exercise enhance neither training induces musclehypertrophynorstrengthoftheelbowflexorsJApplPhysol108:6067,2009.Xsectionalareawasnotdifferentbetween arm only andarm+legresistanceexercise.
AcuteEndocrineinfluences:
Hypothesis: postexercise endocrine responses influence hypertrophy (recurrent mechanical stimuli + increased hormone concentrations such as hGHandTresultinaccentuatedhypertrophyresponsethatsummates summatesover time) Evidenceagainst: 4. Disconnect between postexercise hormone concentrations and hypertrophy response hormone responses to absolute (and likely relative)loadstendtodecreaseaftertraining
Hypertrophy
[Hormone]
Time
EXERCISESTIMULUS
DAMAGE??/TENSION??/ METABOLISM
IMMUNESYSTEM RESPONSE
AUTOCRINE/PARACRINE RESPONSE
ENDOCRINE RESPONSE
Metabolism
MUSCLEREMODELING +
MINOR EFFECT
HYPERTROPHY
AcuteEffectsofPostExerciseHormoneResponses
ChronicEndocrineInfluences
1.Nocontest anabolicsteroidresearch 2.GeneticsandrestingLH,FSHandtestosteroneconcentrations
HarrisJ.A.etal.Theheritabilityoftestosterone:astudyofDutch adolescenttwinsandtheirparents.BehavGenet 28:165171,1998 HoekstraR.A.etal.Heritabilityoftestosteronelevelsin12yearoldtwins anditsrelationtopubertaldevelopment.TwinResHumGenet.9(4):55865,2006 KuijpersE.A.etal.Heritabilityofreproductivehormonesinadultmale twins.HumReprod.:21539,2007 Bogart,G.etal.Heritabilityofbloodconcentrationsofsexsteroidsin relationtobodycompositioninyoungadultmalesiblings.ClinEndocrinol(Oxf). 69:12935.2008
3.Testosterone Heritability+Training
TESTOSTERONE:PRIMARYANDROGEN
PRIMARYANDSECONDARYSEXCHARACTERISTICS