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TheEndocrineSystem:AnOverview

Endocrineglandsareductlessglandsthatproduceandreleasehormonestothebloodthroughdiffusion.
Endocrineglandsmaybestrictlyendocrine,suchasthepituitary,thyroid,parathyroid,adrenal,pinealandthymusor
theymaybeorgansthathavehormoneproductionasoneofmanyfunctions,suchasthepancreas,gonads,
hypothalamus,andothers.

Hormones

ChemistryofHormones

Hormonesarelongdistancechemicalsignalsthataresecretedbythecellstotheextracellularfluidand
regulatethemetabolicfunctionsofothercells.
Mosthormonesareaminoacidbased,butgonadalandadrenocorticalhormonesaresteroids,derivedfrom
cholesterol.
MechanismsofHormoneAction
Hormonestypicallyproducechangesinmembranepermeabilityorpotential,stimulatesynthesisofproteinsor
regulatorymolecules,activateordeactivateenzymes,inducesecretoryactivity,orstimulatemitosis.
Watersolublehormones(allaminoacidbasedhormonesexceptthyroidhormone)exerttheireffectsthroughan
intracellularsecondmessengerthatisactivatedwhenahormonebindstoamembranereceptor.
Secondmessengersystems,activatedwhenahormonebindstoaplasmamembranereceptor,
activateGproteinswithinthecellthatalterenzymeactivity.

Lipidsolublehormones(steroidsandthyroidhormone)diffuseintothecell,wheretheybindtointracellular
receptors,migratetothenucleus,andactivatespecifictargetsequencesofDNA.
Directgeneactivationoccurswhenahormonebindstoanintracellularreceptor,whichactivatesa
specificregionofDNA,causingtheproductionofmRNA,andintitiationofproteinsynthesis.

TargetCellSpecificity
Cellsmusthavespecificmembraneorintracellularreceptorstowhichhormonescanbind.
Targetcellresponsedependsonthreefactors:bloodlevelsofthehormone,relativenumbersoftargetcell
receptors,andaffinityofthereceptorforthehormone.
Targetcellscanchangetheirsensitivitytoahormonebychangingthenumberofreceptors.
HalfLife,Onset,andDurationofHormoneActivity
Theconcentrationofahormonereflectsitsrateofrelease,andtherateofinactivationandremovalfromthe

body.
Thehalflifeofahormoneisthedurationoftimeahormoneremainsintheblood,andisshortestforwater
solublehormones.
Targetorganresponseanddurationofresponsevarywidelyamonghormones.
InteractionofHormonesatTargetCells
Permissivenessoccurswhenonehormonecannotexertitsfulleffectwithoutanotherhormonebeingpresent
(reproductivehormonesneedthyroxinetoproperlystimulatedevelopmentofreproductiveorgans).
Synergismoccurswhenmorethanonehormoneproducesthesameeffectsinatargetcell,andtheircombined
effectsareamplified(glucagon+epinephrinetogetherstimulatemoreglucosereleasefromtheliverthanwhen
eachactsalone).
Antagonismoccurswhenonehormoneopposestheactionofanotherhormone(glucagonantagonizesinsulin).
ControlofHormoneRelease
Mosthormonesynthesisandreleaseisregulatedthroughnegativefeedbackmechanisms.
Endocrineglandstimulimaybehumoral,neural,orhormonal.
Nervoussystemmodulationallowshormonesecretiontobemodifiedbythenervousstimulationinresponseto
changingbodyneeds.

MajorEndocrineOrgans

ThePituitaryGland(Hypophysis)
Thepituitaryglandisconnectedtothehypothalamusviaastalk,theinfundibulum,andconsistsoftwolobes:

theanteriorpituitary,oradenohypophysis,andtheposteriorpituitary,orneurohypophysis.
Twoneurohormonesaresynthesizedbythehypothalamusandsecretedbytheposteriorpituitary.

Oxytocinactsonthesmoothmuscleoftheuterusandbreasttocauseuterinecontractions
duringchildbirthandcontractionofmammarymyoepithelialcells,resultinginmilkexpulsion
(letdownreflex)duringnursing.Oxytocinalsopromotespairbondingbetweenmotherand
child.
Oxytocinisalsoreleasedduringorgasmbutwhetherornotitpromotespairbondingbetween
partnersisdebatable.Thefactthatreleaseisinhibitedbylackofappropriateneuralstimuli
mayspeaktothat.
Antidiuretichormone(ADH)actsonkidneytubulestopromoteincreasedwaterreabsorption
whenbloodvolumeorpressureislow,osmolalityishigh,andsometimespain.Adequate
hydrationinhibitsrelease.
BothoxytocinandADHreleasearealsoinhibitedbyalcohol,whichcanleadtospeculation
aboutdelayingdeliverywithmartinis,rentingbeer,andcoyotelove.

Therearesixadenohypophysealhormonesandoneprohormone.

Growthhormone(GH)indirectly(throughinsulinlikegrowthfactors,IGFs)stimulatesbodycellsto
increaseinsizeanddivide.

Directeffectsareinsulinsparing:mobilizationoffattyacidsforfuel,inhibitionofinsulinactivity,release
ofglucosefromlivertoblood,andstimulationofaminoaciduptakebycells.
GHRH,secretedfromthehypothalamus,isthestimulusforGHrelease.ThestimulusforGHRH
releaseislowbloodlevelsofGHaswellashypoglycemia,lowbloodlevelsoffattyacids,andhigh
bloodlevelsofaminoacids.

HyposecretionofGHresultsinpituitarydwarfisminchildren.HypersecretionofGHinchildhood
resultsingigantisminadulthoodhypersecretionofGHcausesacromegaly(increaseinsizeofflat
bonesafterepiphysealplatesoflongboneshavesealed).

Thyroidstimulatinghormone(TSH)isatropichormonethatstimulatesnormaldevelopmentand
secretionofthethyroidgland.Thryroidreleasinghormone(TRH)fromthehypothalamusstimulates
TSHreleaseThyroidhormone(Thyroxine)exertsnegativefeedbackcontrolofbothTRHandTSH.

Adrenocorticotropichormone(ACTH)isatropichormonestimulatestheadrenalcortextorelease
corticosteroidhormones.
Proopiomelanocortin(POMC)isaprohormonethatisthesourceofadrenocorticotropic
hormone,melanocytestimulatinghormone(which,atnormallevelsactsintheCNS)andtwo
opiates.
Folliclestimulatinghormone(FSH)isatropichormonethatstimulatesgameteproduction.
Leutinizinghormone(LH)isatropichormonethatpromotesovulationinfemalesandproductionof
gonadalhormones.
Prolactinstimulatesmilkproductioninfemales,andmayenhancetestosteroneinmales.

TheThyroidGland
Thethyroidglandconsistsofhollowfollicleswithfolliclecellsthatproducethyroglobulin,and
parafollicularcellsthatproducecalcitonin.

Thyroidhormoneconsistsoftwoaminehormones:thyroxine(T4)andtriiodothyronine(T3),thatacton
allbodycellstoincreasebasalmetabolicrateandbodyheatproduction.

HypothyroidismmayresultfrominadequateTRHrelease,inadequateTSHrelease,dysfunctionofthe
thyroidglanditself,inadequatedietaryiodine,orautoimmunedestruction(Hashimoto'sautoimmune
throiditis).
Fullblownhypothyroidisminadultsisknownasmyxedema(mucousswelling).Ifmyxedema
resultsfromlackofiodinethethyroidglandcontinuestomakethyroglobulinbutiodinateit,
resultinginanenlargedthyroid,orcolloidal/endemicgoiter(figure16a,below).
Treatmenttypicallyinvolvesiodinesupplementation,thyroidhormonesupplementation,and
sometimesablationofthethyroidfollowedbythyroidhormonereplacement.Ablation,which
isalsothetreatmentforGraves'disease,istypicallyaccomplishedbyadministrationof
radioactiveiodine.
Themostcommoncauseofhyperthyroidismisanautoimmunedisease(Graves'disease)inwhich
antiTSHreceptorantibodiesbindtoTSHreceptorsonthethyroidandstimulatecontinuousthyroid
hormonerelease.Thefeedbackmechanismisshortcircuitedbecausetheproductionandreleaseof
thyroidhormoneisnotdependentonTSH.
Exopthalmosmayoccur,indicatingedemaandfibrosisoftissuebehindtheeyes(figure16b,
below).

Calcitonin(producedbyparafollicularor"C"cells)isapeptidehormonethatlowersbloodcalciumby
inhibitingosteoclastactivityandstimulatingCa2+uptakeandincorporationintothebonematrix.

TheParathyroidGlands
Theparathyroidglandscontainchiefcellsthatsecreteparathyroidhormone,orparathormone.

PTHincreasesbloodcalciumlevelsbyaccessingstoredCa++,increasingabsorbtionofCa++,and
inhibitinglossofCa++.
PTHincreasesbloodcalciumlevelsbymobilizingCa++andPO43+frombone,likethefigure
says,butwhatitdoesn'tsayisthatwhenPTHstimulatesCa++reabsorptionatthekidneyit

alsostimulatestheexcretionofPO43+.ThefiguredoespointoutthatPTHincreasesCa++
absorptionbystimulatingrenalactivationofvitaminD3.

TheAdrenal(Suprarenal)Glands
Theadrenalglands,orsuprarenalglands,consistoftworegions:aninneradrenalmedullaandan
outeradrenalcortex.
Theadrenalcortexproducescorticosteroidsfromthreedistinctregions:thezonaglomerulosa,the
zonafasciculata,andthezonareticularis.

Glomerulosa:primarilymineralocorticoids,mostlyaldosterone,areessentialtoregulationof
electrolyteconcentrationsofextracellularfluids(Na+&K+).
Aldosteronesecretionisregulatedbythereninangiotensinmechanism,fluctuating
bloodconcentrationsofsodiumandpotassiumions(increasedsodium
levels/decreasedpotassiumlevels),andsecretionofACTH.

Fasiculata:primarilyglucocorticoidsarereleasedinresponsetostressthroughtheactionof
ACTH.Glucocorticoids,likecortisol,areglucosesparingstressrelatedhormones.
Reticularis:primarilygonadocorticoidsaremostlyweakandrogens,whichareconvertedto
testosteroneandestrogensinthetissuecells.
Cushing'ssyndrome/diseaseiscausedbyanexcessofglucocorticoids.Thediseasemaybecaused
byaglucocorticoidproducingtumorbutinmostcasesadministrationofglucocorticoidsclinically
resultsinthesyndrome.Cushing'ssyndromeischaracterizedbyelevatedbloodglucose,lossof
muscleandproteinfrombone,andhypertensionandedemaduetosaltandwaterretention.Anti
inflammatoryeffectscancauseincreasedsusceptibilitytodiseaseandpoorwoundhealing.

Thesignsinclude"moon"face(duetoedema),andredistributionoffattothebackofthe
neck(buffalohump)andabdomen.

Addison'sdiseaseisadiseaseofcorticalinsufficiency,resultinginweightloss,lowplasmaglucose
andsodiumlevels,andanincreaseinplasmapotassiumlevels.Commonsignsaresevere
dehydrationandhypotension.DisruptionofthefeedbackmechanismthatcontrolsPOMCreleasemay
resultinoverproductionofMSHandageneralbronzing/darkeningoftheskin.
Theadrenalmedullacontainschromaffincellsthatsynthesizeepinephrineandnorepinephrine
(stimulusisacetylcholinereleasedbypreganglionicsympatheticfibers).

ThePancreas
Thepancreasisamixedglandthatcontainsbothendocrineandexocrineglandcells.

Insulinlowersbloodsugarlevelsbyenhancingmembranetransportofglucoseintobody
cells.

Diabetesmellitusisadiseaseofinsulininsufficiency(typeI)orinsulinresistance(typeII),resultinginelevated
bloodglucoselevels.
Glucosespillingintotheurineresultsinosmoticdiuresis,givingrisetodehydrationandincreased
thirst.Inabilityofcellstoutilizeglucoseleadstohunger,allofwhichgiverisetothethreeclassicsigns
ofdiabetes,polyuria,polydipsia,andpolyphagia.
Tomeetenergyneedsofthebodyfatsaremobilizedandproteinsbrokendowntoutilizeaminoacids
forfuel,resultinginmetabolicacidosis.
Longtermcomplicationsincludedecreasedcirculatoryefficiency,peripheralneuropathy,
hypertension,andaccelerationofatherosclerosis.

TypeIdiabetesresultsfromdestructionofpancreaticbetacellsandsubsequentlossofinsulin
production.
Autoimmunedestructionofpancreaticbetacellsappearstobelinkedtocertainviral
infectionsandcorrelateswithHLAhaplotypes(moreintheimmunesystemchapter).
TypeIIdiabetesresultsfrominsulinresistanceandisassociatedwithobesityandgeneticfactors.
Adipocytederivedadiponectinisaninsulinsensitizingandantiatherosclerotichormone,and
recentstudieshavedemonstratedthatadiponectinlevelisagoodpredictorofdeveloping
type2diabetesandcoronaryarterydisease.Decreasingadiponectinlevelsarelinkedtoan
interactionbetweengeneticfactors,suchasmutationsintheadiponectingene,and
environmentalfactors,suchashighfatdiet.
OthercandidatesforinvolvementincludePC1,whichinhibitsphosphorylationoftheinsulin
receptor,andinhibitionormutationsinglucosetransporterproteins(glut4forexample).
TheGonads
Theovariesproduceestrogensandprogesterone.
Thetestesproducetestosterone.
ThePinealGland
Secretesmelatonin,ahormonederivedfromserotonin,inadiurnalcycle.
Indirectlyreceivesinputfromthevisualpathwaysinordertodeterminethetimingofdayandnight.
Lowerlightlevels(onsetofnight)stimulatemelatoninsecretion,whichresultsindrowsiness.Bright
lightstimulatesthebreakdownofmelatonin(levelsarelowestaroundmidday)andhelpsregulateour
diurnalcycle.
Melatoninsecretionisalsoaffectedbythelengthofnightandday,withlevelsbeinghigherinthe
wintermonthsandshorterinthesummer.
Insomeanimalsmatingbehaviorismediatedbymelatoninlevels(howeversexual

response/activityinhumansisacomplexprocess...)andisresponsibleforthe"winterblues"
(SeasonalAffectiveDisorder,S.A.D.)somepeopleexperience.
TheThymus
Thethymusproducesthymopoietin,thymicfactor,andthymosin,whichareessentialforthe
developmentofTlymphocytesandtheimmuneresponse.
ThymopoietingrowthfactorforimmatureTcells
Thymicfactor(thymulin)TcelldifferentiationandenhancementofTandNKcellactions,
neuroendocrineactivity(positivecorrelationbetweenthymulinplasmalevelsandACTHlevels),and
seemstohaveaneffectonproinflammatorycytokines.Analgesicandantiinflammatoryeffectsinthe
CNS.
ThymosinpromotesdifferentiationofT0cellstoT1andlateT2differentiation,accelerates
proliferationofmatureandimmaturelymphoidcells.
OtherHormoneProducingStructures

Theatriaoftheheartcontainspecializedcellsthatsecreteatrialnatriureticpeptide(orfactor,orhormoneANP
orANForANH,dependingonthetext)resultingindecreasedbloodvolume,bloodpressure,andbloodsodium
concentration.
ANPinhibitsaldosteronesecretionandantagonizesitsactivityatthekidney.
Thegastrointestinaltractcontainsenteroendocrinecellsthroughoutthemucosathatsecretehormonesto
regulatedigestivefunctions.
Theplacentasecretesestrogens,progesterone,andhumanchorionicgonadotropin,whichactontheuterusto
influencepregnancy.
Thekidneysproduceerythropoietin,whichsignalsthebonemarrowtoproduceredbloodcells.
Theskinproducescholecalciferol,aninactiveformofvitaminD3.
Adiposetissueproducesleptin,whichactsontheCNStoproduceafeelingofsatiety,andresistin,aninsulin
antagonist.


DevelopmentalAspectsOfTheEndocrineSystem

Endocrineglandsderivedfrommesodermproducesteroidhormonesthosederivedfromectodermor
endodermproduceamines,peptides,orproteinhormones.
Environmentalpollutantshavebeendemonstratedtohaveeffectsonsexhormones,thyroidhormone,and
glucocorticoids.
Oldagemaybringaboutchangesinrateofhormonesecretion,breakdown,excretion,andtargetcell

sensitivity.