Does the GH/IGF system mediate the effect of water

Does the GH/IGF system mediate the effect
by
Jean-Charles GABILLARD (1), Claudine WEIL (1), Pierre-Yves RESCAN (1),
Isabel NAVARRO (2), Joaquim GUTIERREZ (2) & Pierre-Yves LE BAIL (1)
.-Insh,asinallpoikilotherms,growthisstronglydependentonwatertemperature.GiventhattheGH/IGF
systemregulatesgrowth,itcouldmediatetheeffectsoftemperatureonshgrowth.Indeed,beforehatching,thehigher
embryonicgrowthrateinrainbowtroutathightemperaturesisassociatedwithhigherexpressionoftheIGF2geneinthe
wholeembryo.Furthermore,post-natalgrowthuctuationsdependonwatertemperatureandareassociatedwithvariations
ofplasmaGHandIGF1.AlthoughseasonalparameterssuchasphotoperiodandnutritionalstatuscanalsoaffectGH/IGF
systemactivity,ithasbeenshownthatanincreasedtemperatureledtoaspecicincreaseofplasmaGH.Moreover,this
increaseofplasmaGHleadstohigherplasmaIGF1levelsincorrelationwiththegrowthrate.Bycontrast,plasmaIGF2
levelsaswellasmuscularlevelsofIGF1andIGF2mRNAarenotspecicallymodiedbytemperature.Thus,seasonal
uctuationsofwatertemperatureaffectgrowthratethroughadirectactiononplasmaGHandIGF1levels.Themecha-
nismsofthiseffectarenotyetelucidated,butcouldarisefrommodicationsofmetabolitelevels(glucose,aminoacids,
fattyacids,etc.),whichregulateGHsecretiondirectlyorindirectlythroughsomatostatinofpancreaticorhypothalamic
origin.
.-LesystèmeGH/IGFjoue-t-illerôledemédiateurpourl’effetdelatempératuresurlacroissancedupoisson?
Une revue.
Lespoissons,àl’inversedesmammifères,necontrôlentpasleurtempératurecorporelle(poïkilothermes).Cetteparti-
cularitéfaitquelatempératuredumilieumoduleledéveloppementembryonnaireetlacroissancedel’animal.Étantdonné
quelesystèmeGH/IGFpossèdeunrôlecentraldanslarégulationdesprocessusdecroissance,ilpourraitêtrelerelaisdes
effetsdelatempératuresurlacroissance.Aucoursdudéveloppementembryonnaire,nousavonspumontrerquel’augmen-
tationdelavitessededéveloppementembryonnaireinduiteparlatempératureétaitassociéeàuneaugmentationduniveau
desARNmIGF2.Aucoursdelacroissancepost-larvaire,lesvariationssaisonnièresdetempératureentraînentdesvaria-
tionsdecroissance,elles-mêmesassociéesàdesvariationsduniveauplasmatiquedeGHetd’IGF1.Bienquedesparamè-
tressaisonnierstelsquelaphotopériodeetl’étatnutritionnelpuissentmodulerl’activitédusystèmeGH/IGF,ilaétéconr-
méquelatempératureentraîneuneaugmentationspéciqueduniveaucirculantdelaGH.Deplus,celle-ciconduitàune
augmentationdesniveauxcirculantsdel’IGF1,eux-mêmesassociésàlavitessedecroissance.Parcontre,leniveauplas-
matiqued’IGF2ainsiquel’expressionmusculaired’IGF1etd’IGF2nesontpasmodiésparlatempérature.Ainsi,toute
élévationdelatempératureaugmentedirectementleniveaucirculantdeGHetstimulelaproductionendocrined’IGF1,qui
seraitalorsengrandepartieresponsabledesfortstauxdecroissanceobservés.Lesmécanismessous-tendantceteffetne
sontpasencoreélucidés,maispourraientprovenird’unemodicationdesniveauxcirculantsdecertainsmétabolites(glu-
cose,acidesaminés,…)quiréguleraientdirectementouindirectement(somatostatine)lasécrétiondeGH.
Keywords.-Fishgrowth-Temperature-GH/IGFsystem-Review.
Cybium 2005, 29(2): 107-117.
(1) ÉquipeCroissanceetQualitédelaChairdesPoissons,StationCommunedeRecherchesenIchtyophysiologie,Biodiversitéet
EnvironnementSCRIBE–INRA,CampusBeaulieu,35042Rennesc e d e x ,FRANCE.[[email protected]]
(2) DepartamentdeFisiologia,FacultatdeBiologia,UniversitatdeBarcelona,AvingudaDiagonal645,E-08071Barcelona,SPAIN.
Fishareextremelysensitivetoenvironmentalfactors
suchasoxygenlevels,watersalinity,temperature,etc.(Brett,
1979).Giventhatsharepoikilotherms,watertemperature
isamajordeterminingfactorinshbiology.Themostobvi-
ouseffectofhightemperaturesisanincreaseoftheembry-
onicdevelopmentratewithoutaffectingtherelativetiming
offormationoftheanatomicalstructures(Garside,1966;
Vernier,1969;Petersonet al.,1977).Inaddition,eggsincu-
bationatlowtemperatureleads,athatching,totheformation
ofahighernumberofmusclebres(Sticklandet al.,1988;
Usher et al.,1994;Nathanailideset al.,1995)andvertebrae
(Kwain,1975).Ingrowingfish,anincreasedtemperature
leadstoafasterfishgrowthrate,inparallelwithahigher
foodintake(BrettandGroves,1979).
Growthisacomplexfunctionmostlyregulatedbysever-
alhormonesandgrowthfactors.Amongthese,thyroidhor-
mones(T3andT4)areessentialforanormalgrowthrate
andinjectionofT3canpromoteshgrowth(Higgset al.,
1979).Nevertheless,thisgrowthpromotingeffectisthought
tobedependentonotheranabolichormonesbelongingtothe
somatotropicaxis(GH/IGFsystem)(Donaldsonet al.,1979;
MommsenandMoon,2001).Indeed,theuseofGHinjec-
tionsorGHtransgenicshshowedthestrongpotencyofGH
instimulatingshgrowth(McLeanandDonaldson,1993;

Le Bail et al.,1993).Consistentwiththesedata,thelower
growthrateafterGHimmunodepletionprovedtheneedfor
endogenousGHinnormalgrowth(LeBailet al., 1991). In
addition,IGF1injectionincreasesshgrowth(McCormick
et al.,1992;Chenet al.,2000)andendogenousplasmaIGF1
levelsareoftencorrelatedwithgrowthrate(Beckmanand
Dickhoff,1998;Pierceet al.,2001;Mingarroet al.,2002).
AlltheseobservationsraisethepossibilitythattheGH/IGF
systemcanmediatetheeffectsoftemperatureongrowthand
development.
AfterashortdescriptionoftheGH/IGFsysteminsh,
wewillpresentthecurrentknowledgeconcerningtheeffect
oftemperatureontheGH/IGFsystemduringtheembryonic
andpost-larvalperiods.Hypotheses,explainingtheeffects
oftemperatureonGH/IGFsystemactivity,willalsobedis-
cussed.
ThegeneralorganisationoftheGH/IGFsystemissimi-
larinbothhighervertebratesandsh,andincludesgrowth
hormone(GH),GHreceptor,IGF1,IGF2,IGFreceptors,
andIGFbindingproteins(Plisetskayaet al.,1994;Duan,
1997;Kelleyet al.,2000).
Growthhormoneissynthesizedinthepars distalisofthe
pituitaryandwaspuriedinshforthersttimeintilapia
(Oreochromis mossambica)(Farmeret al.,1976).Itsexpres-
sionandsecretiondependonseveralneuropeptides(GHRH,
NPY,SRIF,GnRH,dopamine,etc.)andhormones(T3,
IGF1,IGF2,etc.)(HollowayandLeatherland,1998;Peng
andPeter,1997;PeterandChang,1999).Incontrasttomam-
mals,endogenousbasalsecretionofGHinshisveryhigh
in vitro (Yada et al.,1991;YadaandHirano,1992;Blaiseet
al.,1995a),givingtheinhibitorsofGHsecretionagreater
impact(SRIF,IGFs,etc.).
TheGHreceptor,belongingtothecytokinereceptor
family,hasbeenmainlycharacterizedbybindingstudies,in
severalshspecies(YaoandLeBail,1999;Hirano,1991;
Gray et al.,1992;Nget al.,1992;Yaoet al.,1991;Zhang
andMarchant,1996).RecentlycDNAfortheGHreceptorin
goldsh(Carassius auratus) (Lee et al.,2001),turbot(Pset-
ta maxima)(Calduch-Gineret al.,2001)andseabream
(Sparus aurata)(Calduch-Gineret al.,2003)werecloned
andsequenced,revealingthewell-conservedmotifcharac-
teristicsoftheGHreceptor.Asobservedinmammals,the
liveristhemainorganexpressingtheGHreceptor(Yaoand
LeBail,1999;Yaoet al.,1991;Hirano,1991;Marti-Palanca
andPérez-Sánchez,1994;Calduch-Gineret al.,2001).
IGFs(IGF1andIGF2)arehighlyconservedbetweensh
andmammals(>70%similarity),underlyingtheimportance
ofthesegrowthfactorsthroughoutevolution(Chenet al.,
1994).Consistentwiththe‘Somatomedin’hypothesis,exog-
enousGHstimulatesIGF1expressionintheshliver(Cao
et al.,1989;Shamblottet al.,1995;Moriyama,1995;Dug-
uay et al.,1996;Guillénet al.,1998),whichisthemajor
sourceofcirculatingIGF1(Leroithet al.,2001).Inrainbow
trout(Oncorhynchus mykiss)butnotinothersspecies,GH
canstimulatehepaticIGF2expressionin vivo and in vitro
(Shamblottet al.,1995;LeBailet al.,1998).AlthoughIGF1
functionappearstobelinkedtogrowthregulation(Chenet
al.,1994;BeckmanandDickhoff,1998;Beckmanet al.,
2001;Mingarroet al.,2002),thespecicroleofIGF2isnot
yetknown.Recently,Gabillardet al.(2003c)reportedthat
plasmaIGF2levelsareassociatedwiththenutritionalstatus
ratherthanwiththegrowthrate.
TheIGFtypeIreceptormediatesthebiologicalactions
oftheIGFs.Thisreceptorisaheterotetramer,withtwoextra-
cellularαsubunitsandtwointracellularβsubunits.Theα
subunitcontainstheligand-bindingdomainandtheβ sub-
unitbearsthetyrosinekinasedomainimplicatedinthesig-
naltransduction.Bindingcharacteristicshavebeenstudied
inseveralshspeciesandtheamino-acidsequencesindicate
awell-conservedstructureinteleosts(Navarroet al.,1999;
Planas et al.,2000).Inmammals,asecondIGFreceptor
bindsIGF2:themannose-6-phosphate/IGF2receptor(M6P/
IGF2receptor).Inamphibianandbirdsthisreceptordoes
notbindIGF2duetoalackofaspecicbindingsite(Can-
fieldandKornfeld,1989;Kiesset al.,1994).Therecent
reportofanIGF2bindingtothisreceptorinrainbowtrout
(Mendezet al.,2001)raisesquestionsaboutitsevolution
andfunction.
Asinmammals,IGFscirculateinbloodboundtospecif-
icbindingproteins(IGFBP).Inseveralshspecies,three
formsofIGFBParepresentinblood(Kelleyet al.,2000;
Kelley et al.,2002)withapparentmolecularmassesof29
kDa(IGFBP1),31kDa(IGFBP2)and40-43kDa(IGFBP3).
Theirnucleotidesequencesarenowavailableinzebrash
(Danio rerio) (Duan et al.,1999;MauresandDuan,2002),
seabream(Funkensteinet al.,2002),tilapia(Chenget al.,
2002)andturbot(Duval,2000)anddataconcerningthe
affinityforIGF1andIGF2aswellastheirregulationhas
beguntobereported(Kajimuraet al.,2003;Shimizuet al.,
2003).
Infish,biologicalfunctionsandexternalfactorsinflu-
encetheGH/IGFsystemactivity.Forinstance,salmonsmol-
tificationleadstoanincreaseinplasmalevelsofGHand
IGF1beforetransfertoseawater(Bœuf,1987a;Bœuf,
1987b;Dickhoffet al.,1997).Inaddition,duringsexual
maturationofseveralshspecies,plasmalevelsofGHand
IGF1increase,leadingtoseasonalvariationsofhormonal
Does the GH/IGF system mediate the effect of water temperature on sh growth? Gabillard e t a l .
108 Cybium 2005, 29(2)

profiles(MarchantandPeter,1986;LeGacet al.,1993;
Gomezet al.,1999;Mingarroet al.,2002;Einarsdottiret al.,
2002;Bhandariet al.,2003).
Externalfactorssuchasphotoperiodincreasetheplasma
levelsofGH,whichmayberesponsibleforthestimulation
ofshgrowth(BœufandLeBail,1999).Nutritionalstatus
alsomodulatesGH/IGFsystemactivity.Fastingleadstoan
increaseinplasmaGHlevels,inseveralshspecies(Sumpt-
er et al.,1991;DuanandPlisetskaya,1993;Pérez-Sánchez
et al.,1995;Marchelidonet al.,1996;WeberandGrau,
1999)andinpituitaryGHcontent(Yao,1993;Marchelidon
et al.,1996;WeberandGrau,1999),whilehepaticGH
receptivitydecreases(Grayet al.,1992;Yao,1993;Pérez-
Sánchezet al.,1995).ThishepaticresistancetoGHpartly
explainsthelowerplasmalevelsofIGF1observedinfasted
fish(DuanandPlisetskaya,1993;Moriyamaet al.,1994;
Pérez-Sánchezet al.,1995;Gentilet al.,1996;Bañoset al.,
1999).Inaddition,arecentstudyonrainbowtrout(Chauvi-
gnéet al.,2003)showedanincreaseofIGF1geneexpres-
sioninmuscleafterrefeeding,suggestinganimplicationof
theautocrineand(or)paracrineproductionofIGF1inmus-
clegrowthrecovery.Nevertheless,incasesofmoderatefood
restriction(abovemaintenanceration),plasmaGHlevelsare
unchanged(Pérez-Sánchezet al.,1995;Pierceet al.,2001)
whilehepaticGHreceptivity(Pérez-Sánchezet al.,1995)
andplasmaIGF1levels(Pierceet al.,2001)decreasesimul-
taneously.
Fromtheseobservations,theGH/IGFsystemactivity
appearstodependonparametersthatuctuatethroughthe
seasonsimultaneouslywithwatertemperature.Inconse-
quence,toelucidatethespecicroleoftemperatureonthe
GH/IGFactivity,thesefactorshavetobetakeninaccount.
Somatotrophcellsappearveryearlyduringtheembry-
onicdevelopmentofsalmonids(Malet al.,1989;Sagaet al.,
1993;Naitoet al.,1993;Yanget al.,1999;Joneset al.,2001;
Gabillard et al.,2003b)andIGFsystemmessengershave
beendetectedearlyinembryosofrainbowtrout(Greeneand
Chen,1997;GreeneandChen,1999;Gabillardet al.,
2003b),giltheadseabream(Funkensteinet al.,1996),and
zebrash(Ayasoet al.,2002;Maureset al.,2002;Maures
andDuan,2002).SincetheGH/IGFsystemisinvolvedin
growthinmammals(Leroithet al.,2001),itistemptingto
speculatethatitcouldmediatetheeffectoftemperatureon
embryonicgrowthrate.
Wehaverecentlyinvestigatedthispointsincenodata
wereavailable(Gabillardet al.,2003c).Weshowedinrain-
bowtroutembryos,thatthesomatotrophcellsappearatstage
24(accordingtoVernier,1969),whatevertherearingtem-
perature(4,8or12°C),andthattemperaturedoesnotchange
thelevelsofGHproteinandtranscriptinhatchedembryos.
Therefore,atleastinthisspecies,GHisunlikelytomediate
theeffectoftemperatureonembryonicgrowthrate(Tab.I).
ConcerningtheIGFsystem,IGF1mRNAlevels,inthe
wholeembryoofrainbowtrout,weresimilarat4,8or12°C
(Gabillard et al.,2003c)andthisprobablyresultsfromthe
absenceofvariationsinGHexpression.Bycontrast,an
increaseintheamountofIGF2mRNAwasobservedwith
increasingtemperatures(Fig.1),andisrelatedtothe
enhancementofembryonicgrowthrate.Giventhat,inrain-
bowtroutandzebrashthereisahigherexpressionofIGF2
thanIGF1geneinthewholeembryo(GreeneandChen,
Ga b i l l a r d e t a l . Does the GH/IGF system mediate the effect of water temperature on sh growth?
Cybium 2005, 29(2) 109
4°C8°C 12°C
Stage22 42 21 14
Stage24 48 24 16
Stage25 52 26 17
Hatching814628
TableI.-Duration(days)ofrainbowtroutembryoincubationat4,
8and12°Ctoreachdifferentstagesofdevelopmentaccordingto
Vernier(1969).Stage22:pigmentonthechoroidperiphery,appear-
anceofthecardinalvein.Stage24:6aorticarches,appearanceof
thecaudalvein.Stage25:analnbud,caudalarteryandveinreach
thetailextremity.[Temps (jours) d’incubation à 4, 8 et 12 °C des
embryons de truite arc-en-ciel pour atteindre les différents stades
de développement selon Vernier (1969). Stade 22 : Pigmentation
périphérique de la choroïde, apparition de la veine cardinale. Stade
24 : 6 arcs aortiques, apparition de la veine cardinale. Stade 25 :
bourgeon de la nageoire anale, artère et veine caudales atteignant
l’extrémité de la queue.]
140
120
100
80
60
40
20
0
Stage22 Stage24 Stage25 Hatching
a
bb
a
a
a
ab
ba
a
a
4°C8°C 12°C
Molecules(x104)/µgoftotalRNA
Figure1.-QuantityofIGF2mRNAdeterminedbyrealtimePCR,
inrainbowtroutembryosatstage22,24,25andathatching.
Differencesweredeterminedbythenon-parametricMann-Whitney
U-Test.Differencesbetweenlettersindicateasignicant(p<0.05)
differencebetweenmeanswithinthesamestage.DatafromGabil-
lard et al.(2003b).[Quantité d’ARNm IGF2 déterminée par PCR
en temps réel, chez des embryons de truite arc en ciel aux stades
22, 24, 25 et à l’éclosion. Les différences signicatives sont déter-
minées par le test non-paramétrique de Mann-Whitney. Deux let-
tres différentes indiquent que les moyennes sont différentes pour un
même stade (p < 0,05). Les données proviennent de Gabillard etal.
(2003b).]

1999;Aysonet al.,2002;Maureset al.,2002;Gabillardet
al.,2003b),IGF2couldbeapredominantgrowthfactordur-
ingdevelopmentandwouldpartlyexplaintheeffectsoftem-
peratureontheembryonicgrowthrate.
Seasonal variations of GH/IGF system activity
Seasonalfluctuationsofpost-larvalgrowth(fromfirst
feedingtomaturesh)areassociatedwithwatertemperature
changes.Asinbrowntrout(Salmo trutta),GHinjection
enhancedgrowthratecomparedtocontrolshinMarchbut
notinJuly(Swift,1954),theauthorshypothesizedthat
endogenousGHlevelcouldbehigherinJulythaninMarch.
Consistentwiththishypothesis,SwiftandPickford(1965),
usingabioassay,observedhigherpituitaryGHcontentin
perch(Perca uviatilisL.)duringsummer.Moreover,ahis-
tologicalstudyshowedthatsomatotrophcellsofthebrown
bullhead (Ictalurus nebulosusLesueur)tendtobelarger
(Farbridgeet al.,1985)insummer.Finally,usingradioim-
munologicalassay,itwasconfirmedinchinooksalmon
(Oncorhynchus tshawystscha)(Silversteinet al.,1998),coho
salmon (Oncorhynchus kisutch) (Duan et al.,1995),goldsh
(MarchantandPeter,1986;Marchantet al.,1986)andsea-
bream(Pérez-Sánchezet al.,1994b;Mingarroet al.,2002)
thatplasmaGH(Fig.2)andalsoIGF1(orIGF-like)levels
increasebytheendofspringandduringsummer.Inthelight
oftheseresults,theseasonalhormonalvariationofGHand
IGF1seemstoparalleltheannualuctuationsoftempera-
ture.Itisthustemptingtospeculatethattemperatureregu-
latesplasmalevelsofGHandIGF1.Nevertheless,inthese
studies,othersparameterssuchasphotoperiod,foodintake,
reproductivestagesorthesmolticationprocess,mayinu-
enceGH/IGFsystemactivityandaccountpartlyforthesea-
sonalvariationsofplasmaGHandIGF1levels.
Severalauthorshaveattemptedtoclarifytheinuenceof
watertemperatureonGH/IGFsystemactivity.Undernatural
photoperiod,ahighertemperatureincreasesthelevelsof
plasmaGHinrainbowtrout(BarrettandMcKeown,1989),
aswellasthelevelsofplasmaIGF1insalmonspecies
(Beckmanet al.,1998;McCormicket al.,2000;Larsenet
al.,2001;McCormicket al.,2002)andincatsh(Silverstein
et al.,2000).GiventhatphotoperiodinuencestheGH/IGF
systemactivity,itisnotpossibletodistinguishthespecic
effectoftemperature.Ontheotherhand,underconstantpho-
toperiod,anincreasedtemperaturealwaysraisesplasmaGH
levelsintilapia(Ricordelet al.,1995),turbot(Bœufet al.,
1999),rainbowtrout(Yao,1993)andAtlanticsalmon(Salmo
salar)(Bjornssonet al.,1989).Therefore,seasonalvaria-
tionsofGH/IGFsystemactivitywouldnotresultsolelyfrom
changesinphotoperiod,reinforcingtheideathattempera-
tureisinvolvedinGH/IGFsystemregulation.Nevertheless,
giventhattemperatureinuencesfoodintake(Brett,1979),
itcannotbeexcludedthatvariationsinGH/IGFsystem
activityresultfromdifferencesofnutritionalstatus.
Specic effects of temperature on GH/IGF system activity
Recently,toassesstheputativeinvolvementofnutrition-
alstatusintheeffectoftemperatureonGH/IGFsystem
activity,weperformedtwotypesofexperimentsinrainbow
trout(Gabillardet al.,2003a;Gabillardet al.,2003d).Inthe
rst,shwererearedat8,12or16°Candwerefedad libi-
tumtoobtainshwithdifferentgrowthrates(Fig.3A)and
similarnutritionalstatus(100%ofthead libitumrationat
eachtemperaturestudied).Inthesecond,shwerefedwith
thesamerationtohavesimilargrowth(Fig.3A)despitedis-
tinctnutritionalstatus(90%,70%,50%ofthead libitum
rationat8,1216°Crespectively).Bycomparingtheresults
frombothexperiments,itwaspossibletohighlightthevaria-
tionsofGH/IGFsystemactivitythatmaybespecicallydue
totemperature.
Inbothexperiments,temperaturedidnotlastinglyaffect
IGF1andIGF2mRNAlevelsinmuscle,suggestingthatdif-
ferencesinmusculargrowth,duetotemperature,donot
involvevariationsinmuscularproductionofIGFpeptides.At
Does the GH/IGF system mediate the effect of water temperature on sh growth? Gabillard e t a l .
110 Cybium 2005, 29(2)
Figure2.-Seasonalvariationsinday-
length,watertemperature,plasmaGH
andspecificgrowthrate(SGR)insea
bream (Sparus aurata).Multiplecom-
parisonsamongmeansweremadewith
theDuncanMultipleRangetest.Values
withthesameletterarenotsignicantly
different(p<0.05).DatafromPérez-
Sanchez(1994).[Variations sai-
sonnières de la photopériode, de la
température de l’eau, de la GH plasma-
tique et du taux de croissance spéci-
que chez la daurade (Sparusaurata).
Les comparaisons multiples entre les
moyennes ont été faites avec le test de
Duncan. Les moyennes avec les mêmes
lettres ne sont pas signicativement dif-
férentes (p < 0,05). Les données pro-
viennent de Pérez-Sanchez (1994).]
Nov. Dec. Jan.Fev.Mar.Apr. MayJuneJulyAug. Sept.Oct.
GH(ng/ml)
2
4
6
8
10
12
14
16
18
SGR(%BW/day)
0.0
0.2
0.4
0.6
0.8
1.0
Temperature(°C)
5
10
15
20
25
30
Daylength(h)
8
10
12
14
16
18
20
GH
SGR
a
a
ab
c
bab
ab
Temperature
Daylenght

theendocrinelevel,plasmaIGF2levelsweresimilarinsh
fedad libitumwhateverthetemperature,whileinrestricted
sh,hightemperaturedecreasedthem(Fig.3D).Thus,tem-
peraturedoesnotseemtodirectlyregulateplasmaIGF2lev-
els,whichinsteadtendtoreectthenutritionalstatusofsh.
ForIGF1,aninversesituationwasobserved,sincetempera-
tureincreasedplasmaIGF1levelsonlyinad libitumfedsh
butnotinrestrictedsh(Fig.3C).Inthiscase,theendocrine
productionofIGF1wasclearlyassociatedwiththegrowth
rate,ashasbeenobservedinseveralshspecies(Pérez-Sán-
chezet al.,1994a;Matthewset al.,1997;Duan,1998;Pierce
et al.,2001;Beckmanet al.,2001).Temperatureincreased
plasmaGHlevelsinshfedad libitumaswellasinrestricted
sh(Fig.3B).Theseresultsdemonstratethattheeffectsof
temperatureonplasmaGHlevelsareindependentofthe
nutritionalstatus.Introutfedad libitum,rearingtemperature
increasedgrowthrateproportionallytoplasmaGHlevels.
Thusat8°C,plasmaGHlevelscouldbealimitingfactorof
growthrate.ThepositivecorrelationbetweenplasmaGHand
IGF1(Pearson’scorrelationcoefcientR2=0.10;p<0.01
calculatedbylinearregressionofPearson)inad libitumfed
shsuggeststhathightemperaturesincreaseendocrinepro-
ductionofGH,whichinturnenhancesIGF1expressionin
theliverandplasmaIGF1levels(Gabillardet al.,2003a).
TheabsenceofcorrelationbetweenplasmaGHandIGF1,in
restrictedfish,suggeststhattheGHreceptorexpressionis
lowered,whichremainstobeshown.
Overallthesedatastronglysuggestthatseasonalvaria-
tionsofwatertemperatureaffectgrowthratethroughan
increaseofplasmaGHandIGF1levels.Nevertheless,the
mechanismbywhichtemperatureregulatesGHsecretionis
notyetelucidated.
Effect of temperature on plasma GH levels: Explicative
hypotheses
Recently,severalworkshavereportedthatlowtempera-
turesincreaseplasmainsulinlevelsinvarioussalmonids
(Larsen et al.,2001;Capillaet al.,2003;Gabillardet al.,
2003d).Interestingly,inourexperiments(Gabillardet al.,
2003d),anegativecorrelationwasfoundbetweeninsulin
andGHplasmalevels(Pearson’scorrelationcoefcientR2 =
0.22;p<0.001).Itisunlikelythatendogenousinsulininhib-
itsGHsecretion,sincein vitro,insulinactsatapharmaco-
logicaldose(100-foldhigherthanthephysiologicallevels)
(Blaise et al.,1995b;Rousseauet al.,1998;Duvalet al.,
2002).Nevertheless,insulinsecretagoguesandinsulin-regu-
latedmetabolites,suchasglucose,aminoacids,fattyacids,
couldbeinvolvedintheeffectoftemperatureonplasmaGH
Ga b i l l a r d e t a l . Does the GH/IGF system mediate the effect of water temperature on sh growth?
Cybium 2005, 29(2) 111
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Ad libitum Restricted
SGR(%bw/day)GH(ng/ml)IGF1(ng/ml)IGF2(ng/ml)
D
8°C12°C16°C
a
a
a
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a
a
a
a
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Figure3.-Specicgrowthrate(),plasmaGH(),plasmaIGF1
()andplasmaIGF2(D)ofrainbowtrout(50-60g)rearedatthree
differenttemperatures(8,12and16°C).Fishwerefedad libitum or
restricted(1.2%/bw),andmaintainedundertheseconditionsuntil
theyreachedtheweightof50-60g.Forthead libitumsh,thetime
toreachthisweightwas6,7and10weeksat16,12and8°Crespec-
tively.Therestrictedshweighted50-60gafter12weeks.Differ-
encesweredeterminedbythenon-parametricMann-Whitney
U-Test.Differentlettersindicatedifferences(p<0.05)between
means.DataGabillardet al.,2003c,2003d.[Taux de croissance
spécique (A), niveaux de GH plasmatique (B), d’IGF1 plasmati-
que (C) et d’IGF2 plasmatique (D) chez la truite arc-en-ciel (50-
60 g) élevée à trois températures différentes (8, 12, 16°C). Les pois-
sons ont été nourris à volonté ou restreints (1,2%/poids corporel),
et maintenus dans ces conditions jusqu’à ce qu’ils atteignent le
poids de 50-60 g. Pour les poissons nourris adlibitum, le temps
nécessaire pour atteindre ce poids a été de 6, 7 et 10 semaines à 16,
12 et 8°C respectivement. Les poissons restreints ont atteint 50-60 g
après 12 semaines. Les différences signicatives ont été détermi-
nées par le test U de Mann-Whitney. Des lettres différentes indi-
quent que les moyennes sont signicativement différentes. Données
d’après Gabillard etal., 2003c, 2003d.]