Mechanisms and Biological Significance of Pulsatile Hormone Secretion: Novartis Foundation Symposium 227

278 Pages·2000·2.391 MB·English

by  Novartis Foundation(eds.)

MechanismsandBiologicalSignificanceofPulsatileHormoneSecretion:NovartisFoundation
Symposium227.Volume227
EditedbyDerekJ.ChadwickandJamieA.Goode
CopyrightNovartisFoundation2000.ISBN:0-471-99918-0
MECHANISMS AND
BIOLOGICAL
SIGNIFICANCE OF
PULSATILE
HORMONE SECRETION
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Novartis Foundation Symposium 227
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NovartisFoundationSymposium227
ix+269pages,70¢gures,11tables
LibraryofCongressCataloging-in-PublicationData
Mechanismsandbiologicalsigni¢canceofpulsatilehormonerelease/editors,DerekJ.
ChadwickandJamieA.Goode.
p.cm.^(NovartisFoundationsymposium;227)
SymposiumonMechanismsandBiologicalSigni¢canceofPulsatileHormone
Secretion,heldattheNovartisFoundation,London,2^4March1999.
Includesbibliographicalreferencesandindex.
ISBN0-471-99918-0(hc:alk.paper)
1.Hormones^Secretion^Congresses. 2.Biologicalrhythms^Molecular
aspects^Congresses. I.Chadwick,Derek. II.Goode,Jamie. III.Symposiumon
MechanismsandBiologicalSigni¢canceofPulsatileHormoneSecretion(1999:
London,England)IV.Series.
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Contents
SymposiumonMechanismsandbiologicalsigni¢canceofpulsatilehormonesecretion,heldatthe
NovartisFoundation,London,2^4March1999
Editors:DerekJ.Chadwick(Organizer)andJamieA.Goode
ThissymposiumisbasedonaproposalmadebyFranzSchaeferandJohannesD.Veldhuis
JohannesD.Veldhuis Introduction 1
NicholasS.Foulkes,NicolasCermakian,DavidWhitmoreand
PaoloSassone-Corsi Rhythmictranscription:themolecularbasisof
oscillatorymelatoninsynthesis 5
Discussion 15
AlbertGoldbeter,Genevie'veDupontandJose¤ Halloy Thefrequencyencoding
ofpulsatility 19
Discussion 36
PierreDeMeytsandRonaldM.Shymko Timing-dependentmodulationof
insulinmitogenicversusmetabolicsignalling 46
Discussion 57
DavidJ.Waxman Growthhormonepulse-activatedSTAT5signalling:aunique
regulatorymechanismgoverningsexualdimorphismoflivergeneexpression 61
Discussion 75
StevenM.Pincus Orderlinessofhormonerelease 82
Discussion 96
G.BrabantandK.Prank Predictionandsigni¢canceofthetemporalpatternof
hormonesecretionindiseasestates 105
Discussion 114
FrancisLe¤vi Therapeuticimplicationsofcircadianrhythmsincancerpatients 119
Discussion 136
v
vi CONTENTS
GeorgesCopinschi,KarineSpiegel,RachelLeproultandEveVanCauter
Pathophysiologyofhumancircadianrhythms 143
Discussion 157
JohannesD.Veldhuis Natureofalteredpulsatilehormonereleaseand
neuroendocrinenetworksignallinginhumanageing:clinicalstudiesofthe
somatotropic,gonadotropic,corticotropicandinsulinaxes 163
Discussion 185
PeterButler Pulsatileinsulinsecretion 190
Discussion 199
IainC.A.F.Robinson Controlofgrowthhormone(GH)releasebyGH
secretagogues 206
Discussion 220
FranzSchaefer Pulsatileparathyroidhormonesecretioninhealthanddisease 225
Discussion 239
S.L.Lightman,R.J.Windle,M.D.Julian,M.S.Harbuz,N.Shanks,S.A.Wood,
Y.M.KershawandC.D.Ingram Signi¢canceofpulsatilityintheHPA
axis 244
Discussion 257
JohannesD.Veldhuis Closingremarks 261
Indexofcontributors 263
Subjectindex 265
Participants
GeorgBrabant Abt.KlinischeEndokrinologie,MedizinischeHochschule
Hannover,Carl-Neubergstr.1,D-30623Hannover,Germany
DavidBrown LaboratoryofComputationalNeuroscience,TheBabraham
Institute,CambridgeCB24AT,UK
PeterButler* DepartmentofMedicine,UniversityofEdinburgh,Western
GeneralHospital,EdinburghEH42XU,UK
IainJ.Clarke PrinceHenry’sInstituteofMedicalResearch,POBox5152,
Clayton,VIC3168,Australia
GeorgesCopinschi CentrefortheStudyofBiologicalRhythmsandLaboratory
ofExperimentalMedicine,Universite¤ LibredeBruxelles,808RoutedeLennik,
B-1070Brussels,Belgium
PierreDeMeyts DepartmentofReceptorBiology,HagedornResearch
Institute,NielsSteensensVej6,DK-2820Gentofte,Denmark
Sta¡anEde¤n DepartmentofPhysiology,UniversityofG˛teborg,
Medicinaregatan11,41390Go«teborg,Sweden
AlbertGoldbeter Unite¤ deChronobiologieThe¤orique,Faculte¤ desSciences,
Universite¤ LibredeBruxelles,CampusPlaine,CP231,B-1050Brussels,Belgium
AllanE.Herbison LaboratoryofNeuroendocrinology,TheBabraham
Institute,CambridgeCB24AT,UK
LiseLundKjems(Bursar) DepartmentofMedicine,TheUniversityof
Edinburgh,WesternGeneralHospital,EdinburghEH42XU,UK
*Present address: Division of Endocrinology and Diabetes, Department of Medicine,
UniversityofSouthernCalifornia,1333SanPabloStreet,BMT-B11,LosAngeles,CA90089-
9113,USA
vii
viii PARTICIPANTS
GarethLeng DepartmentofPhysiology,UniversityMedicalSchool,Teviot
Place,EdinburghEH89AG,UK
FrancisLe¤vi LaboratoireRythmesBiologiquesetChronothe¤rapeutique,
InstitutduCanceretd’Immunoge¤ne¤tique.Ho“pitalPaulBrousse,94800
Villejuif,France
JulioLicinio ClinicalNeuroendocrinologyBranch,NationalInstitutesof
MentalHealth,Bldg10,Room2D46,10CenterDrive,Bethesda,
MD20892-1284,USA
Sta¡ordL.Lightman DorothyCrowfootHodgkinLaboratories,Universityof
Bristol,DivisonofMedicine,BristolRoyalIn¢rmary,BristolBS28HW,UK
JohnC.Marshall DepartmentofInternalMedicine,UniversityofVirginia
MedicalCenter,(Box612),Charlottesville,VA22908,USA
DavidR.Matthews Chairman,OxfordCentreforDiabetesEndocrinologyand
Metabolism,TheRadcli¡eIn¢rmary,WoodstockRoad,OxfordOX26HE,UK
AgnetaMode DepartmentofMedicalNutrition,KarolinskaInstitute,Novum,
HuddingeS-14186,Sweden
StevenM.Pincus 990MooseHillRoad,Guilford,CT06437,USA
IainC.A.F.Robinson DivisionofNeurophysiology,NationalInstituteof
MedicalResearch,TheRidgeway,MillHill,LondonNW71AA,UK
PaoloSassone-Corsi InstitutdeGe¤ne¤tiqueetdeBiologieMole¤culaireet
Cellulaire,CNRS-INSERM-ULP,1rueLaurentFries,67404Illkirch-
Strasbourg,France
FranzSchaefer DivisionofPediatricNephrology,UniversityChildren’s
Hospital,ImNeuenheimerFeld150,D-69120Heidelberg,Germany
JohannesD.Veldhuis(Chair) DivisionofEndocrinologyandMetabolism,
DepartmentofInternalMedicineGeneralClinicalResearchCenter,Centerfor
BiomathematicalTechnolgy,UniversityofVirginia,Charlottesville,VA22908,
USA
PARTICIPANTS ix
DavidJ.Waxman DivisionofCellandMolecularBiology,Departmentof
Biology,BostonUniversity,Boston,MA02215,USA
FrederickC.W.Wu DepartmentofEndocrinology,ManchesterRoyal
In¢rmary,OxfordRoad,ManchesterM129WL,UK
MechanismsandBiologicalSignificanceofPulsatileHormoneSecretion:NovartisFoundation
Symposium227.Volume227
EditedbyDerekJ.ChadwickandJamieA.Goode
CopyrightNovartisFoundation2000.ISBN:0-471-99918-0
Introduction
JohannesD.Veldhuis
DivisionofEndocrinologyandMetabolism,DepartmentofInternalMedicineGeneralClinical
Research Center, Center for Biomathematical Technology, University of Virginia,
Charlottesville,VA22908,USA
One of my favourite de¢nitions from the Oxford English Dictionary is that of
wisdom. At this Symposium our assignment is to address the ‘wisdom’ of the
neuroendocrine axis(cid:1)that is, to assess ‘aptness in the choice of ends and the
pursuit of means’ of these pulsatile signalling systems. I take this challenge to
include discussion of the mechanisms by which neuroendocrine signals are
generated, communicated, transduced and fed back. Because of the broad range
of time-scalesinherent in di¡erentbiological signalling systems, the challengeis
particularlycomplex.
By way of an overview, a prototypical signalling axis functions as a well
integrated homeostatic unit. Exactly how this is accomplished in any given
signalling system is not yet well understood. Indeed, whereas one’s research
focus is often directed toward understanding a gene, an enzyme, a structural
feature of a cell or a collection of cells, the physiological merit of homeostatic
signalling is the dynamic ability of the axis to make minute and frequent
adjustments,asnecessary,tomaintainthelifeoftheorganismasawhole.Given
thehierarchicalcontrolswithinanaxis,itwillbeaformidabletaskintheimmediate
futuretoassemblethedetailsofanygivensignallingsystemintoacoherent,well
articulated and comprehensive ensemble. Because most available data consist of
successive measurements of output from only a single signalling element in the
system over time, I believe that success in this lofty aim will require the broad
and concerted interdisciplinary contributions of biomedical, computational and
mathematicalcolleagues.
One proximate goal of this colloquium is to examine critically the more
plausible, and experimentally tractable, hypotheses that predict the biological
relevanceofpulsatilesignallingmechanisms.Mostofourcurrentnotionsabout
signal regulation are not complete, and undoubtedly some are incorrect.
Discussionsinthiscolloquiumshouldchallengeill-supportedviewsandpropose
others,whenappropriate.
Many feedback systems show dominant frequency and/or amplitude control.
Indeed,signalvariationisahallmarkofallaxes.However,theexactsigni¢cance
oftheindividualandmultiplemechanismsofsignalvariationisnotalwaysclear.
1