RadioimmunoassayfortheinvitroquantitativemeasurementofhumanSomatomedin-C(SM-C)inserumandplasma.

BIOLOGicalactivities

Somatomedin-C(SM-C)orInsulin-likegrowthfactorI(IGF-I)isabasic70aminoacidsinglechainpolypeptide(MW:7649Da)similartoproinsulin(50%sequencehomology),andtotheotherwell-characterizedmemberofthesomatomedinfamily:IGFII(67AA,70%sequencehomologywithIGF-I).SM-Cisthemostimportantfactor,whichmediatesthegrowthpromotingactionsofgrowthhormone,apituitaryhormonewithhighlyfluctuatingbloodlevelsduetopulsatilerelease.ThebloodconcentrationofSM-Cismorestableduetothebindingtocarrierproteins.Theconcentrationofthepredominantbindingprotein(MW53000)aswellastheproductionofSM-C,areregulatedbygrowthhormone.SM-Cisproducedbytheliver,andothertissues,andithasendocrine,paracrineandautocrineactivities.Itstimulatesgrowthandregulatesdifferentiationofvarioustissues,displaysinsulin-likeactivitiesandpromotescartilagegrowth.AlthoughGHisthemostimportantfactorcontrollingSM-Csecretionandconcentration,otherfactorsarealsodeterminant:theage(withapeakatadolescence),thesex,thenutritionalstatus,andotherhormones(oestrogen,thyroxin,prolactin,...).SpecifictrophicstimulimainlycontrolSM-Csecretioninthelocalmicroenvironmentofaparticularorgan(paracrineactivities),whilebloodSM-Cconcentrationisthemostimportantvariableforbalancedsystemicgrowth(endocrineactivities).

Clinicalapplications

Growthretardation

Growthretardationmaybeduetoseveralcauses,amongwhichdeficientGHproduction(hypopituitarism),whichisassociatedwithlowSM-Cbloodlevels.BecauseofthedifficultiestogetinterpretableresultsfromGHmeasurements(bydynamicmultipleorstimulationtests),thedeterminationofthestableSM-Cconcentrationinplasmaisoftenconsideredasasimplescreeningtesttoevaluation"GHimpregnation"ofthepatientbeforedecidingmoreextensiveinvestigations.Inseveralclinicalsituationswithimpairedgrowth,lowSM-ClevelsmaybeobserveddespitenormalorhighGHproduction(i.e.malnutrition,chronicdiseasesstates,somegeneticdwarfslikePygmies,...).Interestingly,childrenwithdiscreteGHneuro-secreterydysfunctionmaydisplaylowSM-CvaluesdespitenormalGHlevelsbyconventionaltesting.TheresultsofSM-CassaymustbeinterpretedcautiouslybyconsideringthenormalvariationsofSM-Cduringchildhoodandadolescence(seeRosenfeldetal).

Acromegaly

SM-Clevelsareelevatedinacromegaly(excessproductionofGH)andmayserveasanindicatorofdiseaseseverity.Resultsaremorereadilyinterpretedbecausethenormalvaluesaremoreeasilydefinedinadults.SM-Cmeasurementsarealsousefultomonitortreatment.

Research

TheSM-CRIAkitisaninvaluabletooltostudythemodificationsofthisgrowthfactorduringphysiologic(i.e.pregnancy)orpathologic(i.e.diabetes)situations,andthelocalregulationofSM-Cproductioninrelationtoitsparacrineandautocrineactivities(woundhealing,organregeneration,neoplasticgrowth,foetaldevelopment,gonadalregulation,etc).