Dr. Dicky (Endocrine Fk Regulatory)

8/6/2019 Dr. Dicky (Endocrine Fk Regulatory)

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Endocrine Physiology :Endocrine Physiology :regulation and actionregulation and action

[email protected]@yahoo.com


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Claude Bernard: the father of endocrinology

More than 100 years ago

Claude Bernard stated that

the endocrine system

regulates the internal

milieu of an animal. The

internal secretions or

hormones were liberated

by one part of the body,

traveled via the

bloodstream to distant

targets cells.


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Endocrine system maintainsEndocrine system maintains

homeostasishomeostasis

The concept that hormones acting onThe concept that hormones acting ondistant target cells to maintain thedistant target cells to maintain thestability of the internal milieu was astability of the internal milieu was a

major advance in physiologicalmajor advance in physiologicalunderstanding. The secretion of theunderstanding. The secretion of thehormone was evoked by a change inhormone was evoked by a change inthe milieu and the resulting action onthe milieu and the resulting action onthe target cell restored the milieu tothe target cell restored the milieu tonormal.normal.The desired return to the status quoThe desired return to the status quoresults in the maintenance ofresults in the maintenance ofhomeostasishomeostasis


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Sensing and signalingSensing and signaling

Endocrine glands

synthesize and store

hormones. These glandshave a sensing and

signaling system which

regulate the duration and

magnitude of hormonerelease via feedback from

the target cell.


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Endocrine vs. Nervous SystemEndocrine vs. Nervous System

Major communication systems in theMajor communication systems in thebodybody

Integrate stimuli and responses toIntegrate stimuli and responses tochanges in external and internalchanges in external and internalenvironmentenvironment

Both are crucial to coordinatedBoth are crucial to coordinated

functions of highly differentiatedfunctions of highly differentiatedcells, tissues and organscells, tissues and organs

Unlike the nervous system, theUnlike the nervous system, theendocrine system is anatomicallyendocrine system is anatomically

discontinuous.discontinuous.


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Principal functions of thePrincipal functions of the

endocrine systemendocrine system

MaintenanceMaintenance ofof thethe internalinternal environmentenvironmentinin thethe bodybody (maintaining(maintaining thethe optimumoptimumbiochemicalbiochemical environment)environment)..

IntegrationIntegration andand regulationregulation ofof growthgrowth andanddevelopmentdevelopment..

Control,Control, maintenancemaintenance andand instigationinstigation ofof

sexualsexual reproduction,reproduction, includingincludinggametogenesis,gametogenesis, coitus,coitus, fertilization,fertilization, fetalfetalgrowthgrowth andand developmentdevelopment andand nourishmentnourishmentofof thethe newbornnewborn..


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Hormones travel via theHormones travel via the

bloodstream to target cellsbloodstream to target cells


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Types of cellTypes of cell--toto--cell signalingcell signaling

Classic endocrinehormones travel viabloodstream to targetcells; neurohormones are

released via synapsesand travel via thebloostream; paracrinehormones act on adjacentcells and autocrine

hormones are releasedand act on the cell thatsecreted them. Also,intracrine hormones act

within the cell thatroduces them.


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a specific receptor for thea specific receptor for the

hormonehormone


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Major hormones and systemsMajor hormones and systems

Top down organization of endocrineTop down organization of endocrinesystem.system.

Hypothalamus produces releasing factorsHypothalamus produces releasing factors

that stimulate production of anteriorthat stimulate production of anteriorpituitary hormone which act on peripheralpituitary hormone which act on peripheralendocrine gland to stimulate release ofendocrine gland to stimulate release ofthird hormonethird hormone

Specific examples to followSpecific examples to followPosterior pituitary hormones arePosterior pituitary hormones aresynthesized in neuronal cell bodies in thesynthesized in neuronal cell bodies in thehypothalamus and are released viahypothalamus and are released viasynapses in posterior pituitary.synapses in posterior pituitary. Oxytocin and antidiuretic hormone (ADH)Oxytocin and antidiuretic hormone (ADH)


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Classes of hormonesClasses of hormones

TheThe hormoneshormones fallfall intointo twotwo generalgeneralclassesclasses basedbased onon theirtheir solubilitysolubility ininwaterwater..

TheThe water solublewater soluble hormones are thehormones are thecatecholamines (epinephrine andcatecholamines (epinephrine andnorepinephrine) and peptide/proteinnorepinephrine) and peptide/protein

hormones.hormones.TheThe lipid solublelipid soluble hormones includehormones include

thyroid hormone, steroid hormones andthyroid hormone, steroid hormones andVitamin D3Vitamin D3


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Water soluble hormonesWater soluble hormones

WaterWater solublesoluble hormoneshormones areare synthesizedsynthesized ininendocrineendocrine cellscells andand packagedpackaged intointo secretorysecretorygranulesgranules.. TheseThese granulesgranules fusefuse withwith thethe plasmaplasma membranemembrane inin anan

energyenergy dependentdependent processprocess calledcalled exocytosisexocytosis andand arearereleasedreleased intointo thethe extracellularextracellular fluidfluid surroundingsurrounding thethe cellcell..

WaterWater solublesoluble hormoneshormones areare freelyfreely solublesoluble inin thethebloodstreambloodstream andand cancan traveltravel toto theirtheir targetstargetswithoutwithout beingbeing boundbound toto bloodblood proteinsproteins however,however,

manymany areare associatedassociated withwith bindingbinding proteinsproteins thatthatmodulatemodulate theirtheir bioavailabilitybioavailability


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Lipid soluble hormonesLipid soluble hormones

LipidLipid solublesoluble hormoneshormones areare synthesizedsynthesized ininendocrineendocrine cellscells butbut areare notnot packagedpackaged inin secretorysecretorygranulesgranules..

LipidLipid solublesoluble hormoneshormones passivelypassively diffusediffuse outout ofof

thethe endocrineendocrine cellcell andand becomebecome complexedcomplexed withwithbloodblood proteinsproteins calledcalled globulinsglobulins..

TheThe hormonehormone proteinprotein complexcomplex isis carriedcarried byby thethebloodblood streamstream toto thethe targettarget cellscells wherewhere thethehormonehormone isis releasedreleased fromfrom thethe proteinprotein whichwhichenablesenables itit toto bindbind toto thethe targettarget cellcell receptorreceptor..

SomeSome lipidlipid solublesoluble proteinsproteins dontdont havehave bindingbindingproteins,proteins, forfor example,example, aldosteronealdosterone..


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Types of receptorsTypes of receptors

Receptors for theReceptors for the water soluble hormoneswater soluble hormonesare found on the surface of the target cell,are found on the surface of the target cell,on the plasma membrane.on the plasma membrane.These types of receptors are coupled toThese types of receptors are coupled to

various second messenger systems whichvarious second messenger systems whichmediate the action of the hormone in themediate the action of the hormone in thetarget cell.target cell.

Receptors for theReceptors for the lipid soluble hormoneslipid soluble hormonesreside in the nucleus (and sometimes thereside in the nucleus (and sometimes the

cytoplasm) of the target cell.cytoplasm) of the target cell.Because these hormones can diffuse throughBecause these hormones can diffuse through

the lipid bilayer of the plasma membrane, theirthe lipid bilayer of the plasma membrane, theirreceptors are located on the interior of thereceptors are located on the interior of thetarget celltarget cell


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Hormones and their receptorsHormones and their receptors

Hormone Class of hormone

Location

Amine

(epinephrine)

Water-soluble Cell surface

Amine (thyroidhormone)

Lipid soluble Intracellular

Peptide/protein Water solube Cell surface

Steroids andVitamin D

Lipid Soluble Intracellular


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Second messenger systemsSecond messenger systems

Receptors for the water solubleReceptors for the water solublehormones are found on thehormones are found on the surfacesurfaceof the target cellof the target cell, on the plasma, on the plasmamembrane. These types of receptorsmembrane. These types of receptorsareare coupled to various secondcoupled to various secondmessenger systemsmessenger systems which mediatewhich mediate

the action of the hormone in thethe action of the hormone in thetarget celltarget cell


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Second messengers for cellSecond messengers for cell--

surface receptorssurface receptorsSecondSecond messengermessenger systemssystems includeinclude::

AdenylateAdenylate cyclasecyclase whichwhich catalyzescatalyzes thetheconversionconversion ofof ATPATP toto cycliccyclic AMPAMP;;

GuanylateGuanylate cyclasecyclase whichwhich catalyzescatalyzes thetheconversionconversion ofof GMPGMP toto cycliccyclic GMPGMP (cyclic(cyclic AMPAMPandand cycliccyclic GMPGMP areare knownknown collectivelycollectively asas cycliccyclicnucleotides)nucleotides);;

CalciumCalcium andand calmodulincalmodulin;; phospholipasephospholipase CCwhichwhich catalyzescatalyzes phosphoinositidephosphoinositide turnoverturnoverproducingproducing inositolinositol phosphatesphosphates andand diacyldiacylglycerolglycerol..


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EachEach ofof thesethese secondsecond messengermessenger systemssystemsactivatesactivates aa specificspecific proteinprotein kinasekinase enzymeenzyme..

TheseThese includeinclude cycliccyclic nucleotidenucleotide--dependentdependent

proteinprotein kinaseskinasesCalcium/calmodulinCalcium/calmodulin--dependentdependent proteinprotein kinase,kinase,

andand proteinprotein kinasekinase CC whichwhich dependsdepends onon diacyldiacylglycerolglycerol bindingbinding forfor activationactivation..

ProteinProtein kinasekinase CC activityactivity isis furtherfurther increasedincreased bybycalciumcalcium whichwhich isis releasedreleased byby thethe actionaction ofof inositolinositolphosphatesphosphates..


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The generation of second messengers andThe generation of second messengers andactivation of specific protein kinasesactivation of specific protein kinasesresults in changes in the activity of theresults in changes in the activity of the

target cell which characterizes thetarget cell which characterizes theresponse that the hormone evokes.response that the hormone evokes.

Changes evoked byChanges evoked by the actions of secondthe actions of secondmessengers are usually rapidmessengers are usually rapid


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Cell surface receptor actionCell surface receptor action


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Receptors for lipidReceptors for lipid--solublesolublehormones reside within the cellhormones reside within the cell

Because these hormones can diffuse through theBecause these hormones can diffuse through thelipid bilayer of the plasma membrane, theirlipid bilayer of the plasma membrane, theirreceptors are located on the interior of the targetreceptors are located on the interior of the targetcell.cell.

The lipid soluble hormone diffuses into the cellThe lipid soluble hormone diffuses into the celland binds to the receptor which undergoes aand binds to the receptor which undergoes aconformational change. The receptorconformational change. The receptor--hormonehormonecomplex is then binds to specific DNA sequencescomplex is then binds to specific DNA sequences

called response elements.called response elements. These DNA sequences are in the regulatoryThese DNA sequences are in the regulatory

regions of genes.regions of genes.


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The receptorThe receptor--hormone complex binds to thehormone complex binds to theregulatory region of the gene and changes theregulatory region of the gene and changes theexpression of that gene.expression of that gene.

In most cases binding of receptorIn most cases binding of receptor--hormonehormonecomplex to the gene stimulating the transcriptioncomplex to the gene stimulating the transcriptionof messenger RNA.of messenger RNA.

The messenger RNA travels to the cytoplasmThe messenger RNA travels to the cytoplasmwhere it is translated into protein. The translatedwhere it is translated into protein. The translated

proteins that are produced participate in theproteins that are produced participate in theresponse that is evoked by the hormone in theresponse that is evoked by the hormone in thetarget ctarget cellell

Receptors for lipidReceptors for lipid--solublesolublehormones reside within the cellhormones reside within the cell


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Types of hormonesTypes of hormones--11

AmineAmine hormoneshormones::HormonesHormones derivedderived fromfrom thethe aminoamino acidacid

tyrosinetyrosine..

TheseThese includeinclude epinephrine,epinephrine,norepinephrinenorepinephrine andand thyroidthyroid hormonehormone..EpinephrineEpinephrine andand norepinephrinenorepinephrine areare

producedproduced byby thethe adrenaladrenal medullamedulla waterwatersolublesoluble

ThyroidThyroid hormonehormone isis producedproduced byby thethethyroidthyroid glandgland lipidlipid solublesoluble


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Peptide/proteinPeptide/protein hormoneshormones::RangeRange fromfrom 33 aminoamino acidsacids toto hundredshundreds

ofof aminoamino acidsacids inin sizesize..

OftenOften producedproduced asas largerlarger molecularmolecularweightweight precursorsprecursors thatthat areareproteolyticallyproteolytically cleavedcleaved toto thethe activeactiveformform ofof thethe hormonehormone..

Peptide/proteinPeptide/protein hormoneshormones areare waterwatersolublesoluble..

CompriseComprise thethe largestlargest numbernumber of ofhormoneshormones perhapsperhaps inin thousandsthousands

Types of hormonesTypes of hormones --22


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SteroidSteroid hormoneshormones::

AllAll steroidsteroid hormoneshormones areare derivedderived fromfromcholesterolcholesterol andand differdiffer onlyonly inin thethe ringringstructurestructure andand sideside chainschains attachedattached toto itit..

AllAll steroidsteroid hormoneshormones areare lipidlipid solublesoluble

11,,2525--dihydroxydihydroxy VitaminVitamin DD33 isis alsoalso

derivedderived fromfrom cholesterolcholesterol andand isis lipidlipidsolublesoluble

Types of hormonesTypes of hormones--33


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Peptide/protein hormonesPeptide/protein hormones

AreAre encodedencoded byby aa specificspecific genegene whichwhich isistranscribedtranscribed intointo mRNAmRNA andand translatedtranslated intointo aaproteinprotein precursorprecursor calledcalled aa preprohormonepreprohormone

PreprohormonesPreprohormones areare oftenoften postpost--translationallytranslationallymodifiedmodified inin thethe ERER toto containcontain carbohydratescarbohydrates(glycosylation)(glycosylation)

PreprohormonesPreprohormones containcontain signalsignal peptidespeptides(hydrophobic(hydrophobic aminoamino acids)acids) whichwhich targetstargets themthem toto

thethe golgigolgi wherewhere signalsignal sequencesequence isis removedremoved totoformform prohormoneprohormone

ProhormoneProhormone isis processedprocessed intointo activeactive hormonehormoneandand packagedpackaged intointo secretorysecretory vessiclesvessicles


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Peptide/protein hormonesPeptide/protein hormones

SecretorySecretory vessiclesvessicles movemove toto plasmaplasma membranemembranewherewhere theythey awaitawait aa signalsignal.. ThenThen theythey areareexocytosedexocytosed andand secretedsecreted intointo bloodblood streamstream

In some cases the prohormone is secreted andIn some cases the prohormone is secreted andcoverted in the extracellular fluid into the activecoverted in the extracellular fluid into the activehormone: an example is angiotensin is secretedhormone: an example is angiotensin is secretedby liver and converted into active form byby liver and converted into active form byenzymes secreted by kidney and lungenzymes secreted by kidney and lung


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Peptide/protein hormonePeptide/protein hormone

synthesissynthesis


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Steroid hormonesSteroid hormones

AreAre notnot packaged,packaged, butbut synthesizedsynthesized andandimmediatelyimmediately releasedreleased

Are all derived from the same parent compound:Are all derived from the same parent compound:

CholesterolCholesterolEnzymes which produce steroid hormones fromEnzymes which produce steroid hormones fromcholesterol are located in mitochondria andcholesterol are located in mitochondria andsmooth ERsmooth ER

Steroids are lipid soluble and thus are freelySteroids are lipid soluble and thus are freelypermeable to membranes so are not stored inpermeable to membranes so are not stored incellscells


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Steroid hormonesSteroid hormones

Steroid hormones are not water soluble soSteroid hormones are not water soluble sohave to be carried in the blood complexedhave to be carried in the blood complexedto specific binding globulins.to specific binding globulins.Corticosteroid binding globulin carriesCorticosteroid binding globulin carriescortisolcortisolsex steroid binding globulin carriessex steroid binding globulin carriestestosterone and estradioltestosterone and estradiolIn some cases a steroid is secreted by oneIn some cases a steroid is secreted by one

cell and is converted to the active steroidcell and is converted to the active steroidby the target cell: an example is androgenby the target cell: an example is androgenwhich secreted by the gonad andwhich secreted by the gonad andconverted into estrogen in the brainconverted into estrogen in the brain


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Steroid hormone synthesisSteroid hormone synthesis

All steroid hormones are

derived from cholesterol. A

series of enzymatic steps in the

mitochondria and ER of

steroidogenic tissues convertcholesterol into all of the other

steroid hormones and

intermediates. 1,25-dihydroxy

Vitamin D3 is also derived

from cholesterol


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Steroids can be transformed toSteroids can be transformed to

active steroid in target cellactive steroid in target cell


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Amine hormones:Amine hormones:

derived from tyrosinederived from tyrosine

Epinephrine,Epinephrine, norepinephrinenorepinephrine andanddopaminedopamine areare waterwater solublesoluble andand arearesynthesizedsynthesized andand secretedsecreted likelike peptidepeptidehormoneshormones

ThyroidThyroid hormoneshormones areare producedproduced bybymodificationmodification ofof aa tyrosinetyrosine residueresiduecontainedcontained inin thyroglobulin,thyroglobulin, postpost--translationallytranslationally modifiedmodified toto bindbind iodine,iodine,thenthen proteolyticallyproteolytically cleavedcleaved andand releasedreleasedasas TT44 andand TT33.. TT33 andand TT44 thenthen bindbind totothyroxinthyroxin bindingbinding globulinglobulin forfor transporttransport ininthethe bloodblood


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Synthesis of catecholaminesSynthesis of catecholamines


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Thyroid hormonesThyroid hormones


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Regulation of hormoneRegulation of hormone

secretionsecretion

SensingSensing andand signalingsignaling:: aa biologicalbiological needneed isissensed,sensed, thethe endocrineendocrine systemsystem sendssends outout aasignalsignal toto aa targettarget cellcell whosewhose actionaction

addressesaddresses thethe biologicalbiological needneed.. KeyKeyfeaturesfeatures ofof thisthis stimulusstimulus responseresponse systemsystemareare::

yy receiptreceipt ofof stimulusstimulus

yy synthesissynthesis andand secretionsecretion ofof hormonehormoneyy deliverydelivery ofof hormonehormone toto targettarget cellcell

yy evokingevoking targettarget cellcell responseresponse

yy degradationdegradation ofof hormonehormone


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Feedback controlFeedback control

NegativeNegative feedbackfeedback isis mostmost commoncommon:: forforexample,example, LHLH fromfrom pituitarypituitary stimulatesstimulates thethetestistestis toto produceproduce testosteronetestosterone whichwhich inin

turnturn feedsfeeds backback andand inhibitsinhibits LHLH secretionsecretionPositive feedback is less common:Positive feedback is less common:examples include LH stimulation ofexamples include LH stimulation ofestrogen which stimulates LH surge atestrogen which stimulates LH surge at

ovulationovulation


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Control of hormonal secretionControl of hormonal secretion

HumoralHumoral

NeuralNeural

HormonalHormonal


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Regulation of hormone releaseRegulation of hormone release

1. hormone1. hormone--hormonehormone

2. substrate2. substrate--hormonehormone

3. mineral3. mineral--hormonehormone


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SubstrateSubstrate--hormone controlhormone control

glucose and insulin: as glucoseglucose and insulin: as glucoseincreases it stimulates the pancreasincreases it stimulates the pancreasto secrete insulinto secrete insulin


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Neural controlNeural control

Neural input to hypothalamusNeural input to hypothalamusstimulates synthesis and secretion ofstimulates synthesis and secretion ofreleasing factors which stimulatereleasing factors which stimulatepituitary hormone production andpituitary hormone production andreleaserelease


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Chronotropic controlChronotropic control

Endogenous neuronal rhythmicEndogenous neuronal rhythmicityity

Diurnal rhythms, circadian rhythmsDiurnal rhythms, circadian rhythms

(growth hormone and cortisol),(growth hormone and cortisol),SleepSleep--wake cycle; seasonal rhythmwake cycle; seasonal rhythm


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Circadian (chronotropic) controlCircadian (chronotropic) control


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Circadian ClockCircadian Clock

N ti f db k ff t fN ti f db k ff t f


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Negative feedback effects ofNegative feedback effects ofcortisolcortisol


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Feedback control of insulin byFeedback control of insulin byglucose concentrationsglucose concentrations


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Inputs to endocrine cellsInputs to endocrine cells


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Hormonal interactionsHormonal interactions

PermissivePermissive

SynergisticSynergistic

AntagonisticAntagonistic


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Spare receptorsSpare receptors

TheThe "spare"spare receptor"receptor" conceptconcept isis basedbased onon thisthisrelationshiprelationship andand isis statesstates thatthat maximummaximumbiologicalbiological activityactivity isis oftenoften obtainedobtained whenwhen onlyonly 55toto 1010%% ofof thethe receptorsreceptors areare boundbound..

When the number of spare receptors areWhen the number of spare receptors aredecreased maximum biological activity isdecreased maximum biological activity isachieved at a higher concentration of hormone.achieved at a higher concentration of hormone.Therefore, the greater the number of receptors,Therefore, the greater the number of receptors,

the greater the sensitivity of them to hormonethe greater the sensitivity of them to hormone


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Hormonal measurementsHormonal measurements

BioassayBioassay

anan assayassay systemsystem (animal,(animal, organ,organ, tissue,tissue, cellcell ororenzymeenzyme system)system) isis standardizedstandardized withwith knowknowamountsamounts ofof thethe hormone,hormone, aa standardstandard curvecurve

constructed,constructed, andand thethe activityactivity ofof thethe unknownunknowndetermineddetermined byby comparisoncomparisonexampleexample: testosterone stimulates growth of: testosterone stimulates growth ofprostate gland of immature or castrate rat in aprostate gland of immature or castrate rat in adosedose--dependent manner. Androgen content ofdependent manner. Androgen content ofunknown sample can be determined byunknown sample can be determined by

comparison with testosterone.comparison with testosterone. disadvantagedisadvantage:: cumbersomecumbersome andand difficultdifficult

advantage: measures substance with biologicaladvantage: measures substance with biologicalactivity, not just amountactivity, not just amount


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Original bioassay systemsOriginal bioassay systemsdefined the endocrine systemdefined the endocrine system

Remove endocrine gland and observeRemove endocrine gland and observewhat happenedwhat happened

Prepare crude extract from gland, injectPrepare crude extract from gland, injectback into animal and observe whatback into animal and observe whathappenedhappened

In isolated organ or cell systems, addIn isolated organ or cell systems, add

extract or purified hormonalextract or purified hormonalpreparations and measure biologicalpreparations and measure biologicalresponseresponse


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Hormonal measurementsHormonal measurements

ChemicalChemical methodsmethods

chromatographychromatography

spectrophotometeryspectrophotometery


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HypothalamusHypothalamus

main releasing controler of pituitarymain releasing controler of pituitarysecretionssecretions

production of hormones of posteriorproduction of hormones of posteriorpituitarypituitary

many other control centers heremany other control centers here --ANS, hunger, thirst, temperature,ANS, hunger, thirst, temperature,biological clockbiological clock

General name releasing or inhibitingGeneral name releasing or inhibitinghormone or factorhormone or factor


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ThyrotropinThyrotropin releasing hormonereleasing hormone

TRHTRHGonadotropinGonadotropin

GnRHGnRHCorticotropinCorticotropin

CRHC

RH

Growth hormoneGrowth hormone GHRHGHRH

Growth hormone inhibitingGrowth hormone inhibiting

hormonehormone GHIHGHIH(somatostatin)(somatostatin)

Prolactin inhibiting hormoneProlactin inhibiting hormone

PIH = dopaminePIH = dopamine

ProlactingProlacting -- releasing hormonereleasing hormone


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Growth hormone inhibiting hormoneGrowth hormone inhibiting hormoneGHIH (somatostatin)GHIH (somatostatin)

Prolactin inhibiting hormoneProlactin inhibiting hormone

PIH = dopaminePIH = dopamine

ProlactingProlacting -- releasing hormonereleasing hormonePRHPRH


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Ant ri r it it r Ant ri r it it r

Control of other endocrine glandControl of other endocrine glandsecretions and direct effectssecretions and direct effects

Direct effects:Direct effects:

Somatotropin or Growth hormoneSomatotropin or Growth hormone

ST or GHST or GH

controls metabolism and growthcontrols metabolism and growth

ProlactinProlactin

PRLPRL


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Anterior pituitaryAnterior pituitary

Control of endocrine glands:Control of endocrine glands:

Thyroid stimulating hormoneThyroid stimulating hormone

TSHTSH Secretion of thyroid hormoneSecretion of thyroid hormone

Adrenocorticotropic hormoneAdrenocorticotropic hormoneACTHACTH

Secretion of glucocorticoids, androgens andSecretion of glucocorticoids, androgens andmineralocorticoids to a lesser extentmineralocorticoids to a lesser extent


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Anterior pituitaryAnterior pituitary

Control of endocrine glands:Control of endocrine glands:

Follicle stimulating hormoneFollicle stimulating hormone

FSHFSH follicle growth, estrogen secretionfollicle growth, estrogen secretion

stimulates sperm productionstimulates sperm production

Lutenizing hormoneLutenizing hormoneLHLH triggers ovulation and estrogen andtriggers ovulation and estrogen and

progesterone productionprogesterone production

promotes testosterone productionpromotes testosterone production

P t i Pit itP t i Pit it


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Post riorPit it r Post riorPit it r

Storage and release of hypothalamicStorage and release of hypothalamichormoneshormones

OxytocinOxytocin

OTOT Uterine contractions and milk ejectionUterine contractions and milk ejection

Antidiuretic hormoneAntidiuretic hormone

ADHADH production of concentrated low volume urineproduction of concentrated low volume urine


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PinealPineal

Circadian rhythmsCircadian rhythms

Serotonin, norepinephrine,Serotonin, norepinephrine,dopamine, histamine MAIN melatonindopamine, histamine MAIN melatonin


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ThyroidThyroid

Metabolic rate and CaMetabolic rate and Ca++++ and PO4and PO4--33

balancebalance

Role in growth and developmentRole in growth and development

thyroidthyroid

calcitonincalcitonin


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ParathyroidParathyroid

CaCa++++ and PO4and PO4--33 balancebalance

parathyroid hormoneparathyroid hormone


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ThymusThymus

Immune functionImmune function

thymic hormonesthymic hormones


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Growth HormoneGrowth Hormone

Hypothalamus

Anterior pituitary gland

+ GHRHSomatostatin -

GH

Liver

Cartilage and bonegrowthMuscle and otherorgans:-Protein synthesisand growth

Adipose Tissue-lipolysis- release of FFAs

Most Tissues glucose utilization-o blood glucose

IGF-1

Somatomedin

GH levels and effects are

most pronounced during

puberty


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Control ofGHSecretionControl ofGHSecretion

Stimulation of GH secretionStimulation of GH secretion Blood GlucoseBlood Glucose

Blood Amino Acids, (Arginine, Leucine)Blood Amino Acids, (Arginine, Leucine)

GRH, TRH, ADH, glucagon, dopamine,GRH, TRH, ADH, glucagon, dopamine,

uncontrolled Diabetesuncontrolled Diabetes

DrugsDrugs--Dopamine agonistsDopamine agonists

ExerciseStress sleep pubertyExerciseStress sleep puberty

Inhibition of GH secretionInhibition of GH secretion

SRIF, IGF, hypothyroidismSRIF, IGF, hypothyroidism

Increased Blood GlucoseIncreased Blood Glucose

Dopamine antagonists, chlorpromazineDopamine antagonists, chlorpromazine

Emotional deprivation in children, AgingEmotional deprivation in children, Aging


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Growth hormone disordersGrowth hormone disorders

ExcessGHExcessGH

PrePre--puberty: gigantismpuberty: gigantism oobone growth,bone growth, > 7 ft. tall> 7 ft. tall

PostPost--puberty:acromegalypuberty:acromegaly Sometissuesstill grow:cartilageinnose,Sometissuesstill grow:cartilageinnose,

hands, feet,ridgesofeyebrow,chin,tonguehands, feet,ridgesofeyebrow,chin,tongue

Metaboliceffects:constantincreaseinbloodMetaboliceffects:constantincreaseinbloodsugar,increasedinsulinsugar,increasedinsulin type2diabetes.type2diabetes.

CanalsoincreasemuscleCanalsoincreasemuscle narrowing ofnarrowing ofarteries,heartattackarteries,heartattack


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GH DeficiencyGH Deficiency

GH,GH, IGFIGF--11

Short statureShort stature

Metabolic effectsMetabolic effects

Recombinant human GH (RnGH)Recombinant human GH (RnGH) FirstusedtotreatGHDFirstusedtotreatGHD

Supplyof RnGHhasmadeitpossibletosupplyGH forSupplyof RnGHhasmadeitpossibletosupplyGH forgeneralshortnessgeneralshortness

Metaboliceffects:accelerationofpuberty,Metaboliceffects:accelerationofpuberty,pancreatitis,intercranialhypertension,maypancreatitis,intercranialhypertension,may riskofriskof

leukemia,strokeleukemia,stroke


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Sources ofIGFSources ofIGF--1 Production1 Production

IGFIGF--1 primary site of production is1 primary site of production isLiverLiver Primarily Controlled by GHPrimarily Controlled by GH

IGFIGF--1 Produced in bone1 Produced in bone Controlled by PTH (Parathyroid Hormone) andControlled by PTH (Parathyroid Hormone) andEE22

IGFIGF--2 Produced in Fetus2 Produced in Fetus Controlled by PRL and hPL in fetusControlled by PRL and hPL in fetus


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IGFIGF--1 &1 & --2 Metabolic Actions2 Metabolic Actions

Regulate Cellular ProliferationRegulate Cellular Proliferation(Stimulate)(Stimulate)

Stimulate Cellular DifferentiationStimulate Cellular Differentiation

Stimulate Cellular MetabolismStimulate Cellular Metabolism

Resemble ProResemble Pro--Insulin in Structure andInsulin in Structure andFunctionFunction

IGFIGF--1 = 42% structural homology with pro1 = 42% structural homology with pro--insulininsulin


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Endocrine, Autocrine and ParacrineEndocrine, Autocrine and ParacrineFunctionsFunctions

IGFIGF--2 produced in Fetal Tissues2 produced in Fetal Tissues--Converts to IGFConverts to IGF--1 in children and1 in children andadultsadults

IGFIGF--1 &1 & --2 act on type I IGF2 act on type I IGF

receptors (Tyr Kin)receptors (Tyr Kin)


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Profound effects on Bone andProfound effects on Bone andCartilageCartilage

Stimulate Chondrocytes (CartilageStimulate Chondrocytes (Cartilageforming cells)forming cells)

Are MitogenicAre Mitogenic

Stimulate Osteoblasts (under PTHStimulate Osteoblasts (under PTHand Eand E22))

Stimulate collagen formationStimulate collagen formation


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Stimulate Bone Matrix formationStimulate Bone Matrix formation

Results of all above:Results of all above:

Increase long bone length in preIncrease long bone length in pre--pubescentpubescentchildrenchildren

increase periosteal growth throughout lifeincrease periosteal growth throughout life

increase cartilage growth (chondrocytes)increase cartilage growth (chondrocytes)

increase bone matrix formationincrease bone matrix formation

Mimic Insulin EffectsMimic Insulin EffectsMinimal effectiveness related to InsulinMinimal effectiveness related to Insulin


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Effects MuscleEffects Muscle

Increases Muscular proliferationIncreases Muscular proliferation

+DNA, +RNA, +Protein Synthesis+DNA, +RNA, +Protein Synthesis

Hypothalamic EffectsHypothalamic EffectsDecreases GRH releaseDecreases GRH release


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Mimic Insulin EffectsMimic Insulin Effects

Stimulate Glucose UptakeStimulate Glucose Uptake

Stimulate Amino Acid UptakeStimulate Amino Acid Uptake

Cross reactions between Insulin andCross reactions between Insulin andIGFIGF-- ReceptorsReceptors

receptor classes are similar and to EGFreceptor classes are similar and to EGF(Epidermal Growth Factor) receptors(Epidermal Growth Factor) receptors

But, Minimal effectiveness related toBut, Minimal effectiveness related toInsulinInsulin

Adr nalsAdr nals


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Adr nalsAdr nals

Stress responseStress response

cortexcortex -- mineralocorticoids,mineralocorticoids,glucocorticoids and gonadocorticoidsglucocorticoids and gonadocorticoids

medullamedulla -- which is of course part of thewhich is of course part of thesympathetic NS but acts in an endocrinesympathetic NS but acts in an endocrinefunction to prolong the sympatheticfunction to prolong the sympatheticresponseresponse


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Adrenal hormoneAdrenal hormone

Adrenal MedullaAdrenal Medulla

Situated directly atop each kidney andSituated directly atop each kidney andstimulated by the sympathetic nervousstimulated by the sympathetic nervous

systemsystemSecretes the catecholaminesSecretes the catecholamines

EpinephrineEpinephrine: elicits a fight or flight: elicits a fight or flightresponseresponse

Increase H.R. and B.P.Increase H.R. and B.P.

Increase respirationIncrease respiration


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Increase metabolic rateIncrease metabolic rate

Increase glycogenolysisIncrease glycogenolysis

VasodilationVasodilation

NorepinephrineNorepinephrineHouse keeping systemHouse keeping system


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Adrenal CortexAdrenal Cortex

Secretes over 30 different steroidSecretes over 30 different steroidhormones (corticosteroids)hormones (corticosteroids)

MineralocorticoidsMineralocorticoidsAldosterone: maintains electrolyte balanceAldosterone: maintains electrolyte balance

GlucocorticoidsGlucocorticoids

Cortisol:Cortisol:Mobilization of free fatty acidsMobilization of free fatty acids

Glucose sparingGlucose sparing

GonadocorticoidsGonadocorticoids

testosterone estro en ro esteronetestosterone estro en ro esterone


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Adrenal glucocorticoidsAdrenal glucocorticoids

Noeffecton growthinnormalNoeffecton growthinnormalamountsamounts

Cortisol,corticosteronelevelsCortisol,corticosteronelevelsoo

during stressand / ordiseasetoduring stressand / ordiseasetohelpadapthelpadapt

Decreasesblood glucoseuptakeintoDecreasesblood glucoseuptakeintotissuestissues

AntagonizesinsulinAntagonizesinsulin


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Increasesbreakdown fromtissuesIncreasesbreakdown fromtissues

LiverLiver-- gluconeogenesisgluconeogenesis

Increases glucosesubstratesIncreases glucosesubstrates

Enhances fatbreakdownEnhances fatbreakdown

VeryCATABOLIC (breaksdownVeryCATABOLIC (breaksdowneverythingeverything including bone)including bone)

AntiAnti--inflammatory agentinflammatory agent


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InsulinInsulin

HormoneofFeastingHormoneofFeasting FromPancreasFromPancreas-- FF cells fromIsletsofcells fromIsletsof

LangerhansLangerhans Allows glucosetoenterthecellAllows glucosetoenterthecell

oo glucose uptake into tissuesglucose uptake into tissues Affects glucose transporterAffects glucose transporter

EnergyEnergy MetabolicProcessesMetabolicProcesses

Glycogen synthesisGlycogen synthesis Fat synthesisFat synthesis

Protein synthesisProtein synthesis

GrowthGrowth

ChildrenwithpoorlycontrolledTypeIdiabetesoftenChildrenwithpoorlycontrolledTypeIdiabetesoftenhaveshortstaturehaveshortstature


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Insulin DeficiencyInsulin Deficiency

LipolysisLipolysis

FFAFFA ketone bodiesketone bodies acidifies bloodacidifies blood

Protein breakdownProtein breakdown

Plasma GlucosePlasma Glucose

Osmotic diuresisOsmotic diuresis

water excretionwater excretion

qq plasma volumeplasma volume qq arterial blood pressurearterial blood pressure

qq brain blood flowbrain blood flow


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GonadsGonads


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Reproductive functionReproductive function

Female estrogens and progesteroneFemale estrogens and progesterone

Males testosteroneMales testosterone

Other organs which produceOther organs which produce


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hormoneshormones

GI tractGI tractStomachStomach -- gastrin and serotoningastrin and serotonin

in stomach release of HCl and contractionin stomach release of HCl and contraction

DuodenumDuodenum -- secretin and cholecyctokininsecretin and cholecyctokinin

in pancreas release of bicarbonate andin pancreas release of bicarbonate andenzymesenzymes

KidneyKidney-- erythropoetinerythropoetin production ofRBCs in bone marrowproduction ofRBCs in bone marrow



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hormoneshormones

SkinSkin-- cholecalciferolcholecalciferol from vitamin D activated in the kidneysfrom vitamin D activated in the kidneys

to calcitirol promotes Cato calcitirol promotes Ca++++

absorptionabsorption

HeartHeart -- atrial natriuretic factor ( ANF)atrial natriuretic factor ( ANF) in kidneys inhibits Na+ reabsoption andin kidneys inhibits Na+ reabsoption and

renin release and inhibits secretion ofrenin release and inhibits secretion ofaldosterone by the adrenal cortexaldosterone by the adrenal cortex

PlacentaPlacenta-- a bunch of hormones includinga bunch of hormones including

Documents

Dr. Dicky (Endocrine Fk Regulatory)