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HORMONES OF ADRENAL MEDULLA

HORMONES OF ADRENAL MEDULLA. Prof.Dr .Arzu SEVEN. Sympathoadrenal system. Parasympathetic nervous system with cholinergic pre and postganglionic nerves. Sympathetic nervous system with cholinergic preganglionic and adrenergic postganglionic nerves + 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

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