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HORMONES OF ADRENAL MEDULLA

HORMONES OF ADRENAL MEDULLA

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HORMONES OF ADRENAL MEDULLA

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  1. HORMONES OF ADRENAL MEDULLA Prof.Dr.Arzu SEVEN

  2. Sympathoadrenalsystem Parasympathetic nervoussystem with cholinergicpreand postganglionicnerves Sympathetic nervoussystem withcholinergic preganglionicand adrenergicpostganglionic nerves + adrenal medulla

  3. Adrenal medulla is actually an extension of thesympatheticnervoussystemwherechoromaffincellsproducecatecholaminehormones: • Dopamine • Norepinephrine • Epinephrine(80%)

  4. Adrenal medulla is a specializedganglionwithoutaxonalextension • Itschromaffincellssynthesize , storeandreleasehormonesendocrine organ • Catecholaminesaremajorelements in responseto severe stress

  5. Stresshormones: • Catecholamines • Glucocorticoids • Growthhormone • Vasopressin • Angiotensin II • Glucagon

  6. Conversion of tyrosinetoepinephrinerequires 4 sequentialsteps; • Ring hydroxylation • Decarboxylation • Side-chainhydroxylation • N_methylation

  7. Tyrosinehydroxylase is the rate limitingenzyme • Itfunctions as an oxidoreductase , withtetrahydropteridine as a cofactor • Feedbackinhibitionbycatecholamines • Competitivelyinhibitedbytyrosinederivatives - α_methyltyrosineandbyα,α,dipyridyl • Catecholaminescan’tcrosstheblood_brainbarrier

  8. L_Dopa, theprecursor of dopamine, readilycrossesthebloodbrainbarrierused in thetreatment of Parkinson’sdisease • Dopadecarboxylaserequirespyridoxalphosphate , competetivelyinhibitedbyα metil dopa • Dopamineβhydroxylase (DBH) is a mixedfunctionoxidase, usesascorbate as an electrondonor, copper at theactive site andfumarate as modulator,conversionoccurs in thesecretiongranule • PNMT is inducedbyglucocorticoidhormones ,conversionoccurs in thecytoplasm

  9. Catecolaminesenterthegranulevia an ATP_dependent transport mechanismandbindsthisnucleotide in a 4:1 ratio(hormone:ATP) • NE is stored in thesegranules, can be N_methylated • Exocytoticrelease of NE and E arecalciumdependentandarestimulatedbycholinergicandβ_adrenergicagentsandinhibitedbyα_adrenergicagents

  10. The adrenal medulla, unlikethesympatheticnerves, does not have a mechanismforthereuptakeandstorage of dischargedcatecholamines • Theepinephrinedischargedfromthe adrenal goestotheliverandskeletalmuscle • Verylittle adrenal NE reachesdistaltissues

  11. Catecholaminescirculate in plasma in a looseassociationwithalbumin • Theyhave an extremelyshortbiologicalhalf life (10-30 sec.)

  12. Catecholaminesarerapidlymetabolizedbycatechol_O_methyltransferase(COMT) andmonoamineoxidase (MAO) to form O_methylatedanddeaminatedmetabolites

  13. Theconcentration of metanephrinesor VMA in urine is elevated in > 95% of patientswithPHEOCHROMOCYTOMA • Tumor of adrenal medullaNE causeshypertensionbyactivatingα_1_adrenoceptors on vascularsmoothmuscle, andepinephrineincreasesheart rate byactivationβ1_adrenoceptors • Hypertensionmay be paroxysmaland severe, leadingtostrokeorheartfailure

  14. Catecholamines can be classifiedbytheirmechanism at action. Theyactthrough 2 majorclasses of receptors ; • αadrenergic • β adrenergic

  15. α1 • α • Β • α2 β1 β2

  16. Epinephrinebindsandactivatesbothαandβreceptors • NE at physiologicconcentrationsprimarilybindstoαreceptors • Thecatecholaminereceptorsaremembers of the G protein-linkedclass of receptor • Hormonesthatbindtoβ1, γ, β2 receptorsactivateadenylylcyclase, whereashormonesthatbindtoα2 receptorsinhibittheenzyme

  17. α1 receptorsarecoupledtoprocessesthatalterintracellularCaconcentrationsormodifyphosphatidylinositide met. (orboth) +2