ControlofSecretionRate

Mosthormonescontrolledbynegativefeedback
systems
Mosthormonesarenotsecretedatconstantrate,
buttheirsecretionisregulatedbythreedifferent
methods
1. Theactionofasubstanceotherthanahormoneonan
endocrinegland.
2. Neuralcontrolofendocrinegland.
3. Controlofsecretoryactivityofoneendocrinegland
byhormoneorneurohormonesecretedbyanother
endocrinegland
1. Humoralstimulus:ActionofSubstance
OtherThanHormone
Anincreasedbloodglucose
concentrationstimulates
increasedinsulinsecretionfrom
thepancreas
Insulinincreasesglucose
uptakebytissues,which
decreasesbloodglucoselevels.
Autonomicnervoussystemalso
influencesinsulinsecretion
HypocalcemiastimulatesPTH
secretionfromparathyroids
Hypersecretionstimulates
calcitoninfromparafollicular
cells
2. NervousSystemRegulation
Stimulisuchasstressor
exerciseactivatethe
sympatheticdivisionofthe
autonomicnervoussystem
Sympatheticneuronsstimulate
thereleaseofepinephrineand
smalleramountsof
norepinephrinefromtheadrenal
medulla.Epinephrineand
norepinephrinepreparethe
bodytorespondtostressful
conditions.
Oncethestressfulstimuliare
removed,lessepinephrineis
releasedasaresultofdecreased
stimulationfromtheautonomic
nervoussystem.
 3. HormonalRegulation
Secretionoftropic
homonesfromhypotha
lamusstimulatessecre
tionofanteriorpituitary
homrones.
ExampleshowsTRH
(thyrotropicreleasing
hormone)fromhypotha
lamusstimulatingsecre
tionofTSHfromanterior
pituitary.
Note:TSHitselfisa
tropichormoneinthatit
stimulatesT3/T4secretion.
 PositiveandNegativeFeedback
POSITIVE
Duringthemenstrualcycle,before
ovulation,smallamountsof
estrogenaresecretedfromthe
ovary.
Estrogenstimulatesthereleaseof
gonadotropinreleasinghormone
(GnRH)fromthehypothalamus
andluteinizinghormone(LH)from
theanteriorpituitary
GnRHalsostimulatestherelease
ofLHfromtheanteriorpituitary
LHcausesthereleaseofadditional
estrogenfromtheovary.The
GnRHandLHlevelsintheblood
increasebecauseofthispositive
feedbackeffect.
PositiveandNegativeFeedback
NEGATIVE
Duringthemenstrualcycle,
afterovulation,theovary
beginstosecrete
progesteroneinresponseto
LH.
Progesteroneinhibitsthe
releaseofGnRHfromthe
hypothalamusandLHfrom
theanteriorpituitary.
DecreasedGnRHrelease
fromthehypothalamus
reducesLHsecretionfrom
theanteriorpituitary.GnRH
andLHlevelsintheblood
decreasebecauseofthis
negativefeedbackeffect.
ChangesinHormoneSecretion
ThroughTime
a) Chronichormoneregulation.
Maintenanceofrelatively
constantconcentrationof
hormone.Thyroidhormone.
b) Acutehormoneregulation.
Epinephrineinresponseto
stress.
c) Cyclichormoneregulation.
Femalereproductive
hormones.
 Transportand
Hormonesdissolveinbloodplasmaand
aretransportedinfreeformorare
Distribution
reversiblyboundtoplasmaproteins
Freeformcandiffusefromplasmainto
interstitialfluidandaffectcells
Asconcentrationoffreehormone
moleculesincrease,morehormones
moleculesdiffusefromcapillariesinto
interstitialspacestobindtotargetcells
Lipidsolublehormonesdiffusethrough
capillarycells.Watersolublehormones
diffusethroughporesincapillariescalled
fenestrae.
Alargedecreaseinplasmaprotein
concentrationcanresultinlossofa
hormonefromthebloodbecausefree
hormonesarerapidlyeliminatedfrom
circulationthroughkidneyorliver
Hormonesaredistributedquicklybecause
theycirculateintheblood
 MetabolismandExcretion
Halflife:Thelengthof
timeittakesforhalfa
doseofsubstancetobe
eliminatedfrom
circulatorysystem
Longhalflife:regulate
activitiesthatremainata
constantratethrough
time.Usuallylipid
solubleandtravelin
plasmaattachedto
proteins
Shorthalflife:water
solublehormonesas
proteins,epinephrine,
norepinephrine.Havea
rapidonsetandshort
duration
Hormone(Ligand)InteractionwithTarget
Tissues
Portionofmoleculewhereligand
bindsiscalledbindingsite.
Ifthemoleculeisareceptor(likein
acellmembrane)thebindingsiteis
calledareceptorsite
Ligand/receptorsiteisspecific;e.g.,
epinephrinecannotbindtothe
receptorsiteforinsulin.
Thepurposeofbindingtotarget
tissueistoelicitaresponsebythe
targetcell.
 Down Normally,receptormoleculesare
degradedandreplacedonaregular
Regulation basis.
Downregulation
Rateatwhichreceptorsaresynthesized
decreasesinsomecellsafterthecells
areexposedtoaligand.
Combinationofligandsandreceptors
canincreasetherateatwhichreceptor
moleculesaredegraded.This
combinedformistakenintothecellby
phagocytosisandthenbrokendown.
Tissuesthatexhibitdown
regulationareadaptedtoshortterm
increasesinhormoneconcentration.

Tissuesthatrespondtohormones
maintainedatconstantlevels
normallydonotexhibitdown
regulation.
 UpRegulation
Somestimuluscausesincrease
insynthesisofreceptorsfora
hormone,thusincreases
sensitivitytothathormone
Forexample,FSHstimulation
oftheovarycausesanincrease
ofLHreceptors.Ovariancells
arenowmoresensitivetoLH,
eveniftheconcentrationofLH
doesnotchange.Thiscauses
ovulation.
MembraneBoundReceptors
Receptor:integralproteinswithreceptor
siteatextracellularsurface.Interactwith
ligandsthatcannotpassthroughthe
plasmamembrane.
Ligands
Watersolubleorlargemolecular
weighthormones.Attachmentof
ligandcausesintracellularreaction.
Largeproteins,glycoproteins,
polypeptides;smallermoleculeslike
epinephrineandnorepinephrine
IntracellularReceptors
Receptors:inthecytoplasmor
inthenucleus
Ligands
Lipidsolubleand
relativelysmallmolecules;
passthroughtheplasma
membrane.
Reacteitherwithenzymes
inthecytoplasmorwith
DNAtocause
transcriptionand
translation
Thyroidhormones,
testosterone,estrogen,
progesterone,aldosterone,
andcortisol
 MembraneBoundReceptors
Proteinsorglycoproteinsthathavepolypeptidechains
foldedtocrosscellmembraneseveraltimes
Ligandbindsreversiblytoreceptorsiteonreceptorprotein
Threedifferentresultsofligandbinding
1. Alterationofmembranepermeability.Example:
acetylcholine
2. ActivationofGproteinsassociatedwiththe
membrane,causesproductionofintracellularmediator
suchascyclicAMP,leadstoactivationofintracellular
enzymes.Example:LH
3. Receptorslinkedtointracellularenzymesthrough
intracellularmediators.Mediatorsalteractivityof
intracellularenzymes.Examples:nitricoxide,
cyclicGMP,Caions.
 IntracellularReceptors
Proteinsincytoplasmornucleus
Hormonesbindwithintracellularreceptorand
receptorhormonecomplexactivatecertaingenes,
causestranscriptionofmRNAandtranslation.These
proteins(enzymes)producetheresponseofthetarget
celltothehormone
Latentperiodofseveralhoursbecausetimeisrequired
toproducemRNAandprotein
Processeslimitedbybreakdownofreceptorhormone
complex
Estrogenandtestosteroneproducedifferentproteinsin
cellsthatcausethedifferingsecondarysexual
characteristicsoffemalesandmales.
 Anatomy and Physiology, Seventh Edition
RodR.Seeley
IdahoStateUniversity
TrentD.Stephens
IdahoStateUniversity
PhilipTate
PhoenixCollege

Chapter 18
Lecture Outline*
*See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.

CopyrightTheMcGrawHillCompanies,Inc.Permissionrequiredforreproductionordisplay.
 EndocrineSystemFunctions

Metabolismandtissuematuration
Ionregulation
Waterbalance
Immunesystemregulation
Heartrateandbloodpressureregulation
Controlofbloodglucoseandothernutrients
Controlofreproductivefunctions
Uterinecontractionsandmilkrelease
PituitaryGlandand
Hypothalamus
Wherenervousand
endocrinesystemsinteract
Hypothalamusregulates
secretionsofanterior
pituitary
Posteriorpituitaryisan
extensionofthe
hypothalamus
Anteriorpituitaryproduces
ninemajorhormonesthat
Regulatebodyfunctions
Regulatethesecretionsof
otherendocrineglands
PituitaryGlandStructure
Posteriorpituitary
(neurohypophysis):extension
ofthenervoussystemviathe
infundibulum
Secretesneurohormones
Anteriorpituitary
(adenohypophysis)
Consistsofthreeareaswith
indistinctboundaries:pars
distalis,parsintermedia,pars
tuberalis
Hypothalamus,AnteriorPituitary,andTargetTissues
 ReleasingandInhibitingHormones
Tropinsortropichormones:hormonesthatregulatethehormonesecretions
oftargetendocrinetissues.Allanteriorpituitaryhormonesaretropins.
Releasinghormonessecretedbythehypothalamus:
GHRH.Growthhormonereleasinghormone.Causestheanterior
pituitarytoreleasegrowthhormone.
TRH.Thyroidreleasinghormone.Causestheanteriorpituitaryto
releasethyroidstimulatinghormone(TSH).
CRH.Corticotropinreleasinghormone.Causesanteriorpituitaryto
produceadrenocorticotropichormone(ACTH)
GnRH.Gonadotropinreleasinghormone.Causesanteriorpituitaryto
produceFSH(folliclestimulatinghormone)andLH(luteinizing
hormone).
PRH.Prolactinreleasinghormone.Causestheanteriorpituitaryto
releaseprolactin.
Inhibitinghormones:
GHIH.Growthhormoneinhibitinghormone,somatostatin.Causes
theanteriorpituitarytodecreasereleaseofgrowthhormone.
PIH.Prolactininhibitinghormone.Causestheanteriorpituitaryto
decreasereleaseofprolactin.
 Hypothalamus,PosteriorPituitaryandTarget
Tissues
Hypothalamicneurons
syntheiszeADHand
oxytocin.
Latterhormonestravel
topost.pituitaryvia
axonsofhypothalamic
neurons.
ADHandoxytocin
entercirculationinpost.
pituitary.
 HormonesofPosteriorPituitary:ADH
Antidiuretichormone(ADH).Alsocalledvasopressin.
A. Osmoreceptors(specializedneuronsof
hypothalamusmonitorchangesinintercellular
osmolality(relativeconcentrationsofelectrolytesand
water).Iftheconcentrationofelectrolytesincreases
oriftheconcentrationofwaterdecreases,thenADH
secretionisstimulated.
B. Baroreceptors(specializedneuronsfoundinwallsof
atriaofheart,largeveins,carotidarteries,aorticarch)
sensechangesinbloodpressure(BP).IfBP
decreases,thenADHsecretionisstimulated.
ControlofADHSecretion
ControlofOxytocinSecretion
 AnteriorPituitaryHormones
Growthhormone(GH)orsomatotropin
Thyroidstimulatinghormone(TSH)
Adrenocorticotropichormone(ACTH)
Melanocytestimulatinghormone(MSH)
Betaendorphins
Lipotropins
Luteinizinghormone(LH)
Folliclestimulatinghormone(FSH)
Prolactin
 GrowthHormone(GHorsomatotropin)
Stimulatesuptakeofaminoacids;protein
synthesis;growthinmosttissues.
Stimulatesbreakdownoffatstobeusedas
anenergysourcebutstimulatessynthesisof
glycogen:glucosesparing
Promotesboneandcartilagegrowth
Regulatesbloodlevelsofnutrientsaftera
mealandduringperiodsoffasting
Stimulatesglucosesynthesisbyliver
MetabolicActionofGrowth
Hormone

Figure 16.6
GrowthHormoneStimulation:functionsin
regulatinggrowth,tissuemaintenance,metabolism
GHRHfromhypothalamuscausesreleaseof
Growthhormonefromanteriorpituitaryeffects
Targettissues:mosttissuesofthebody
Directeffect:GHbindstoreceptorsoncellsandcauses
changeswithinthecells.Increasedlipolysisanddecreased
useofglucoseforenergy
Indirecteffect:causesliverandskeletalmuscletoproduce
somatomedins;e.g.,insulinlikegrowthfactors(IGFs)
Insulinlikegrowthfactors:bindtoreceptorson
membranesoftargetcells.Stimulategrowthin
cartilage,bone;increasedsynthesisofproteinsin
skeletalmuscle.
 RegulationofGHSecretion
1.Stressanddecreasedglucose
levelsincreasereleaseofGHRH
anddecreasereleaseofGHIH.
2.GHRHandGHINtravelvia
thehypothalamohypophyseal
portalsystemtoant.pituitary
3.IncreasedGHRHandreduced
GHIHactonAPandresultin
increasedGHsecretion.
4.GHactsontargettissues.
5.IncreasingGHlevelshaveneg
feedbackeffectonhypothala.
 GrowthHormone:Inhibition
Hypothalamusproducesgrowthhormoneinhibitinghormone
(GHIH=somatostatin)
InhibitsproductionofGHbyanteriorpituitary.
GHRHsecretioninresponsetolowbloodglucose,stress,
increaseincertaina.a.
GHIHsecretionsinresponsetohighbloodglucose.
PeakGHlevelsduringdeepsleep;levelsloweratothertimes
ofday.
HyposecretionofGHmayresultindwarfism
Hypersecretionmayresultingiantismoracromegalyde
pendingonossificationofepiphysealplates
 TSHandThyroidHormones
TRHfromhypothalamuscausestherelease
ofTSHfromanteriorpituitarywhich
causessecretionandstorageofhormones
T3andT4fromandwithinthethyroidgland
TSHincreasesactivityofphospholipase
thatopensCa2+channels,increasingCa2+
concentrationincellsofthethyroidgland
T3andT4inhibitTRHandTSHsecretion
AdrenocorticotrophicHormone(ACTH)

CRHfromhypothalamuscausesreleaseof
ACTHfromanteriorpituitarywhich
Causescortisolsecretionfromtheadrenal
cortex(aglucocorticoidfromthezona
fasciculata)
Causesaldosteronesecretionfromthe
adrenalcortex(amineralocorticoidfrom
thezonaglomerulosa)
Bindsdirectlytomelanocytesoftheskin;
causesincreaseinproductionofmelanin.
 MelanocyteStimulatingHormone,
Endorphins,andLipotropins
ACTH,MSH,endorphinsandlipotropinsallderived
fromthesamelargeprecursormoleculewhenstimulated
byCRH
MSHcausesmelanocytestoproducemoremelanin
Endorphinsactasananalgesic;producedduringtimesof
stress.
Lipotropinscauseadiposecellstocatabolizefat
 LH,FSH,Prolactin
Gonadotrophs:glycoproteinhormonesthatpromote
growthandfunctionofthegonads
LHandFSH
Bothhormonesregulateproductionofgametesand
reproductivehormones
Testosteroneinmales
Estrogenandprogesteroneinfemales
GnRHfromhypothalamusstimulatesLHandFSH
secretion
Prolactin:roleinmilkproduction
Regulationofsecretion:prolactinreleasinghormone(PRH)
andprolactininhibitinghormones(PIH)
Thyroid Oneoflargestendocrineglands;Highly
vascular.Iodineentersfollicularcellsbyactive
Gland
transport.Onlyglandthatstoreshormone.
Histology
Composedoffollicles:follicularcells
surroundingthyroglobulin/thyroid
hormones
Parafollicularcells:betweenfollicles
Physiology
Follicularcellssecretethyroglobulininto
lumenoffollicle.Iodineanda.a.tyrosine
necessaryforproductionofT3andT4.
Hormonesstoredhereattachedtothe
thyroglobulinthenabsorbedintofollicular
cells;hormonesdisattachedfrom
thyroglobulinandreleasedintocirculation.
Parafollicularcells.Secretecalcitonin
whichreduces[Ca2+]inbodyfluidswhen
Calevelsareelevated.
BiosynthesisofThyroid
Hormones
 ThyroidHormones
Producedbyfollicularcells
TriiodothyronineorT3lessproduced
TetraiodothyronineorT4orthyroxinemore
99.6%ofthyroxineinthebloodisboundtothyroxine
bindingglobulin(TBG)fromtheliver.Restisfree.
TBGhasahigheraffinityforT4thanforT3;amtoffree
unboundT3inplasmais10xsgreaterthanfreeT 4.
OnlyfreethyroxineandT3canentercells;bound
thyroxineservesasareservoirofthishormone
3340%ofT4convertedtoT3incells:T3morepotent
Bindwithintracellularreceptormoleculesandinitiate
newproteinsynthesis
Increaserateofglucose,fat,proteinmetabolisminmany
tissuesthusincreasingbodytemperature
Normalgrowthofmanytissuesdependentonpresenceof
thyroidhormones.
EffectsofT3andT4
1.Maintainnormalrateofmetabolism.
2.Increasetherateatwhichglucose,fat,andproteinaremeta
bolized.
3.IncreasetheactivityofNa+K+pumpwhichincreasesbody
temperature.
4.Canalterthenumberandactivityofmitochondriaresultingin
greaterATPsynthesisandheatproduction.
5.Normalgrowthandmaturationofbone,hair,teeth,c.t.,and
nervoustissuerequirethyroidhormone.
6.BothT3andT4playapermissiveroleforGHandGHdoesnot
haveitsnormaleffectontissuesifT3andT4arelacking.
7.SeeTable18.4foreffectsofhypoandhypersecretion
RegulationofT3andT4Secretion

 RegulationofCalcitoninSecretion

Producedbyparafollicularcells
SecretiontriggeredbyhighCa 2+
concentrationinblood;actstodecrease
Ca2+concentration
Primarytargettissue:bone.Decreases
osteoclastactivity,lengthenslifespan
ofosteoblasts.
ParathyroidGlands
Embeddedinthyroid
Twoglandsoneachside
SecretePTH:targettissuesare
bone,kidneysandintestines.
Increasesbloodcalciumand
phosphatelevels
Stimulatesosteoclasts
Promotescalciumreabsorptionby
kidneysandPO4excretion
IncreasessynthesisofvitaminD
which,inturn,increasesabsorption
ofCaandPO4byintestines.Net
lossofPO4underinfluenceof
PTH.
Regulationdependsoncalcium
levels.
EffectsofParathyroidHormone

Figure 16.11
AdrenalGlands
Nearsuperiorpolesof
kidneys;retroperitoneal
Innermedulla;outer
cortex
Medulla:formedfrom
neuralcrest;sympathetic.
Secretesepinephrineand
norepinephrine
Cortex:threezonesfrom
superficialtodeep
Zonaglomerulosa
Zonafasciculata
Zonareticularis
 AdrenalMedulla
Secretoryproductsareneurohormones:epinephrineandnorepinephrine
Combinewithadrenergicmembraneboundreceptors
AllfunctionthroughGproteinmechanisms
Secretionofhormonespreparesbodyforphysicalactivity
Effectsareshortlived;hormonesrapidlymetabolized
Epinephrine
Increasesbloodlevelsofglucose
Increasesfatbreakdowninadiposetissue
Causesdilationofbloodvesselsinskeletalmusclesandcardiacmuscles.
Epinephrineandnorepinephrineincreaseheartrateandforceofcontraction;
causebloodvesselstoconstrictinskin,kidneys,gastrointestinaltract,and
otherviscera
 HormonesofAdrenalCortex
Mineralocorticoids:Zonaglomerulosa
Aldosteroneproducedingreatestamounts.Increases
rateofsodiumreabsorptionbykidneysincreasing
sodiumbloodlevels
Glucocorticoids:Zonafasciculata
Cortisolismajorhormone.Increasesfatandprotein
breakdown,increasesglucosesynthesis,decreases
inflammatoryresponse
Androgens:Zonareticularis
Weakandrogenssecretedthenconvertedto
testosteronebyperipheraltissues.Stimulatepubicand
axillaryhairgrowthandsexualdriveinfemales
RegulationofCortisolSecretion
 Glucocorticoids(Cortisol)

Helpthebodyresiststressby:
Keepingbloodsugarlevelsrelativelyconstant
Maintainingbloodvolumeandpreventingwatershift
intotissue
Cortisolprovokes:
Gluconeogenesis(formationofglucosefrom
noncarbohydrates)
Risesinbloodglucose,fattyacids,andaminoacids
StressandtheAdrenalGland

Figure 16.15
Pancreas
Locatedalongsmallintestineand
stomach;retroperitoneal
Exocrinegland
Producespancreaticdigestive
juices
Endocrinegland
Consistsofpancreaticislets
Composedof
Alphacells;secreteglucagon
Betacells;secreteinsulin
Deltacells;secretesomatostatin
 Glucagon

A29aminoacidpolypeptidehormonethatisa
potenthyperglycemicagent
Itsmajortargetistheliver,whereitpromotes:
Glycogenolysisthebreakdownofglycogento
glucose
Gluconeogenesissynthesisofglucosefromlacticacid
andnoncarbohydrates
Releaseofglucosetothebloodfromlivercells
 Insulin
Targettissueistheliver,adiposetissue,muscle,
andsatietycenterofhypothalamus
A51aminoacidproteinconsistingoftwoamino
acidchainslinkedbydisulfidebonds
Synthesizedaspartofproinsulinandthenexcised
byenzymes,releasingfunctionalinsulin
Insulin:
Lowersbloodglucoselevels
Enhancestransportofglucoseintobodycells
Countersmetabolicactivitythatwouldenhanceblood
glucoselevels
 RegulationofBloodGlucoseLevels

The
hyperglycemic
effectsof
glucagonand
the
hypoglycemic
effectsof
insulin
Figure 16.17
 DiabetesMellitus(DM)

Resultsfromhyposecretionorhypoactivityof
insulin
ThethreecardinalsignsofDMare:
Polyuriahugeurineoutput
Polydipsiaexcessivethirst
Polyphagiaexcessivehungerandfoodconsumption
Hyperinsulinismexcessiveinsulinsecretion,
resultinginhypoglycemia
DiabetesMellitus(DM)

Figure 16.18
RegulationofInsulinSecretion
RegulationofBloodNutrientLevels
RegulationofBloodNutrientLevels
DuringExercise
HormonesoftheReproductiveSystem
Male:Testes
Testosterone
Regulatesproductionofsperm
cellsanddevelopmentand
maintenanceofmale
reproductiveorgansand
secondarysexcharacteristics
Inhibin
InhibitsFSHsecretion
Female:Ovaries
EstrogenandProgesterone
Uterineandmammarygland
developmentandfunction,
externalgenitaliastructure,
secondarysexcharacteristics,
menstrualcycle
Inhibin
InhibitsFSHsecretion
Relaxin
Increasesflexibilityof
symphysispubis
 PinealBody
Inepithalamus;producesmelatoninandarginine
vasotocin
 ThymusGland,GITract,Kidneys
Thymosin.Developmentoftheimmune
system.
GItract:severalhormonesregulate
digestionandenzymesecretion.Studied
withdigestivesystem.
Kidneyssecreteerythropoietin,which
signalstheproductionofredbloodcells
Adiposetissuereleasesleptin,whichis
involvedinthesensationofsatiety,and
stimulatesincreasedenergyexpenditure
 HormonelikeSubstances
Autocrines:chemicalsignalsreleasedbyacellandthe
substanceaffectsthatsamecell.
Chemicalmediatorsofinflammationwhichare
modifiedfattyacids:eicosanoidssuchas
prostaglandins,thromboxanes,prostacyclins,and
leukotrienes
Paracrines:chemicalsignalsreleasedintointercellular
fluidandaffectingnearbycells.
Endorphinsandenkephalinsmodulatesensationofpain
Severalgrowthfactors
 EffectsofAgingon
EndocrineSystem
Gradualdecreaseinsecretoryactivityofsomeglands
GHaspeopleageexceptinpeoplewhoexerciseregularly
Melatonin
Thyroidhormones
Kidneyssecretelessrenin
FamilialtendencytodeveloptypeIIdiabetes