sistemul endocrin- introducere
TRANSCRIPT
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PRINCIPII GENERALE IN ENDOCRINOLOGIE
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SISTEMUL ENDOCRIN
• Intervine in reglarea : - cresterii si dezvoltarii; - reproducerii; - producerii, utilizarii si stocarii energiei.• Este alcatuit din : - celule endocrine – dispersate /grupate
in glande endocrine; - hormonii secretati ; - receptorii hormonali ai celulelor tinta.
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ENDOCRINOLOGIA
anatomia si fiziologia glandelor endocrine;
• produsii de secretie ai glandelor endocrine;
• mecanismele de actiune ale hormonilor;
manifestarile clinice ale disfunctiilor hormonale.
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GLANDELE ENDOCRINE
- Glande cu secretie interna ce sintetizeaza si elibereaza in circulatia sanguina sau in spatiul intercelular substante chimice numite hormoni .
- Hormonii ajung la nivelul celulelor tinta si exercita variate actiuni prin legare de receptori specifici (efecte biologice apriori programate).
- Hormon= a pune in miscare.
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HORMONII PRODUSI DE CELULELE NERVOASE
- NEUROHORMONI – se elibereaza in circulatia sanguina si actioneaza la distanta;
- NEUROMODULATORI – se elibereaza in spatiul intercelular , avand actiune autocrina sau paracrina;
- NEUROTRANSMITATORI – se elibereaza la nivelul fantelor sinaptice neuronale.
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ORIGINEA EMBRIOLOGICA A GLANDELOR ENDOCRINE
- ECTODERM - adenohipofiza ;
- medulosuprarenale;
- pineala.
- ENDODERM - tiroida;
- paratiroide;
- pancreas.
- MEZODERM - corticosuprarenale;
- gonade.
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STRUCTURA CHIMICA A HORMONILOR
- PEPTIDE SI PROTEINE (glicoproteine)=sintetizati in glandele de origine ecto- si endodermala.- DERIVATI DE
AMINOACIZI :catecolaminehistamina, serotonina, hormoni tiroidieni.- STEROIZI : vitamina D, hormonisintetizati in glandele de originemezodermala.- PROSTAGLANDINE – hormoni tisulari.
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SINTEZA HORMONILOR
HORMONII PROTEICI SI POLIPEPTIDICI
- Activare genicatranscriptia genicatranslatie
- Pre-pro-hormonprohormonhormon bioactiv
- Se stocheaza in granule secretorii.
- Se elibereaza extracelular prin exocitoza.
- Pot fi prezenti in citoplasma ca proteine libere sau complexe cu componentele celulare.
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SINTEZA HORMONILOR
HORMONII STEROIZI- Sinteza porneste de la precursorul colesterol.- Este necesara activarea unor enzime specifice
din celulele endocrine, care catalizeaza reactiile de transformare a precursorului in produsul finit
- Moleculele de hormon steroid sunt liposolubile, pot difuza din celule.- Sinteza este continua si nu exista rezerve de
hormon in organism(exceptie fac hormonii tiroidieni,vitamina D ).
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TRANSPORTUL HORMONILOR
Hormonii peptidici si proteici sunt hidrosolubili → circula liberi
Hormonii steroizi si hormonii tiroidieni sunt hidrofobi
→ circula in mare parte legati de proteine plasmatice→ fractia libera constituie fractia biologic activa
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PROTEINELE DE TRANSPORT
CBG (cortizol, progesteron, aldosteron)
SHBG (estrogeni, androgeni)
TBG (hormoni tiroidieni)
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TRANSPORTUL HORMONILOR
PROTEINELE DE TRANSPORT
- permit accesul hormonilor hidrofobi la nivelul celulelor ;
- au functie de rezervor, ce corecteaza rapid modificarile nivelelor hormonale ;
- afecteaza clearance-ul plasmatic ;
- au capacitate de legare >>concentratiile fiziologice ale hormonilor.
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MECANISMELE DE ACTIUNE ALE HORMONILOR
RECEPTORUL
= macromolecula specializata cu situsuri cu stereospecificitate pentru hormoni;
- Este situat la nivelul membranei celulare , intracelular sau in nucleu.
- Capteaza, concentreaza si leaga reversibil hormonul care il activeaza transmite mesajulefect.
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Receptorii membranari
Hormoni hidrosolubili:
• Hormonii hipotalamo-hipofizari
• PTH
• Catecolamine
• Insulina, glucagon
• IGF 1
• Leptina
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Receptorii pentru hormonii proteici si polipeptidici
- Sunt receptori membranari ;
- Cuplarea hormonului cu receptorul activarea sistemului mesagerului secund ;
- Receptorii se asociaza cu proteine G (stimulatoare/inhibitoare ), ce leaga receptorul de unitatile catalitice.
- Exemplu :ATPAMPcproteinkinaza A cascada de fosforilariamplificarea semnalului
initial.
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Receptori intracelulari
Hormoni liposolubili:
• Glucocorticoizi
• Mineralocorticoizi
• Estradiol, androgeni, progesteron
• Triiodotironine
• 1,25dihidroxi Vitamina D
• Acid retinoic
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Receptorii intracelulari
- Citoplasmatici sau nucleari.
- Complexul hormon/receptor intra in nucleu, se leaga de o secventa AND transcriptia genica ARNm trece prin membrana nucleara ribozomi: sinteza de proteine.
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RECEPTORUL - CARACTERISTICI
CONCENTRATIA
- receptori larg raspanditi : insulina, E2,T,hipofiza
- receptori cu distributie limitata: aldosteron.
- receptori cu concentratie crescuta in anumite tesuturi: R pentru E2 in uter,vagin,san.
AFINITATEA
= specificitate cu care sunt activati de o anumita molecula – agonisti/antagonisti.
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REGLAREA ACTIVITATII SISTEMULUI ENDOCRIN
Se realizeaza la doua nivele principale :
- productia hormonala in glanda endocrina;
- receptorilor specifici in tesuturile tinta.
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Reglarea la nivelul productiei
Se realizeaza prin trei mecanisme :
- Feed-back
- Neurogen
- Bioritm
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Mecanismele de feed-back
Feed-back negativ - bucla lunga - intre hormonii periferici / tropii
hipofizari si hormonii hipotalamici;- bucla scurta – intre hormonii hipofizari si cei
hipotalamici ;- bucla ultrascurta – activa la nivelul
hipotalamusului; hormonii hipotalamici isi inhiba propria eliberare.
Feed-back pozitiv- Intre E2 si GnRH / FSH,LH preovulator.
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Feed–back–ul negativ
Marea majoritate a hormonilor sunt tinuti sub control prin feed-back negativ
Exemplu:
oGlicemie → glucagon
oCalcemia → PTH
oVolumul de fluid extracelular → ADH, renina
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Reglarea neurogena
- Intervine in raspunsul nespecific la stress.
- Exista 4 transductori neuroendocrini ce transforma informatia nervoasa in mesaj hormonal : hipotalamusul, MSR, pineala, pancreasul.
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Reglarea prin bioritm
- Ultradian – periodicitate de ore sau minute<24 ore : GnRH, TRH, PRL, insulina, testosteron.
- Circadian – periodicitate de 24 ore: cortizol.
- Circatrigintan – periodicitate de 30 zile: ciclul menstrual
- Circanual – variabilitate sezoniera a T4 si T.
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Reglarea la nivel de receptor
Factori genetici → numarul si sensibilitatea receptorilor (ex: R pentru androgeni)
Starea de diferentiere a celulei si ciclul celular
Factori endocrino-metabolici (ex: hormoni tiroidieni – R β adrenergici)
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Reglarea la nivel de receptor
Actiune de tip “up-regulation” a propriului receptor (ex: hormonii androgeni)
Actiune de “down-regulation” a propriului receptor (ex: insulina, GHRH)
Actiune asupra receptorilor altor hormoni (ex: progesteron – receptor androgenic)
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ACTIUNILE HORMONILOR
1.Un hormon exercita mai multe actiuni datorita distributiei largi a receptorilor sai.
Ex. Testosteronul determina :- Sexualizarea organismului masculin in timpul
vietii intrauterine.- Cresterea pilozitatii faciale si corporeale.- Dezvoltarea musculaturii.- Controlul spermatogenezei.- Stimuleaza sinteza de eritropoetina.- Alopecie de tip androgen.
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ACTIUNILE HORMONILOR
2. O functie presupune actiunea mai multor hormoni .
Exemplu:
- in mentinerea glicemiei intervin insulina, glucagonul, cortizolul, GH, catecolamine, somatostatinul, GIP.
- in lactatie: PRL,hPL,glucocorticoizii,GH, hormoni tiroidieni, estrogeni,progesteron, oxitocina
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MECANISMELE ETIOPATOGENICE ALE BOLILOR ENDOCRINE
1.MODIFICARILE PRODUCTIEI HORMONALE
- exces - tumori benigne/maligne - sub stimulul unor imunoglobuline:TRab - tranzitoriu (ex: tiroidita subacuta).
- deficit-agenezie/disgenezie (ex: mixedem congenital)
- deficite enzimatice (ex: sdr adreno-genital congenital)
- procese distructive ale glandei (ex: TBC suprarenal, necroza hipofizara postpartum,iradiere,chirurgie)
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MECANISMELE ETIOPATOGENICE ALE BOLILOR ENDOCRINE
2. ALTERAREA MECANISMELOR DE FEED-BACK.
3. ALTERAREA BIORITMURILOR:
- pubertate precoce
- SOP
- anovulatie
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MECANISMELE ETIOPATOGENICE ALE BOLILOR ENDOCRINE
4. PATOLOGIE DE RECEPTOR
Ex. - rezistenta la hormoni tiroidieni
- rezistenta la insulina
- diabetul insipid nefrogen
- nanismul Laron
- sindrom testiculului feminizant
- pseudohipoparatiroidismul
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MECANISMELE ETIOPATOGENICE ALE BOLILOR ENDOCRINE
5. ANOMALII ALE PROTEINELOR DE TRANSPORT- nu determina patologie endocrina pentru ca intervin mecanismele de feed-back.
6. ANOMALII HORMONALE MULTIPLE
- sindromul MEN tip I si II (hiperfunctie)
- sindroame poliglandulare (hipofunctie).