HORMONII TIROIDIENI

T4 tetraiodotironina sau tiroxina

T3- triiodotironina

ESENAILI PT. VIA

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 GLANDA TIROID
Unitatea funcional: foliculul tiroidian cu o retea capilar bogat
- foliculii
Coloidul- tiroidieni
soluia concentrata de tireoglobulin (100 Tyr/molecula)

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 Hormonii tiroidieni

Precursor:
Tironina

Formele active:
Tetraiodotironina

Triiodotironina

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 Sinteza T3 i T4
Glanda tiroid: singurul esut din corp care
poate acumula iod, prin intermediul unei
pompe specifice
1) Captarea ioni iodura (I-) din plasma
1) Surse
2) mecanism thyroid epithelium
2) Oxidarea iodului la suprafata apicala a
celulelor tiroidiene (tireoperoxidaza) si
iodurarea Tyr din tireoglobulina
(organificarea iodului) cu formarea de MIT
si DIT
3) Cuplarea MIT si DIT luminal colloid
-MIT +DIT produce T3
-DIT+DIT, T4.
4) Endocitoza tireoglobulinei din coloid in celule,
hidroliza proteinei, eliberarea T3 i T4 si 4
Thyroid Follicles

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Thyroid Hormone Synthesis

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 SINTEZA HH TIROIDIENI ETAPA IODURAREA Tyr

TYR HO Tyr CH2CHCOOH- TIREOGLOBULINA

NH2

IODURARE
TIROZINA I

HO CH2CHCOOH-
MONOIODOTIROZINA (MIT) Tyr TIREOGLOBULINA

NH2

IODURARE
TIROZINA Aprox. 10% din returile de Tyr ale tireoglobinei pot fi
I iodurate, (situruri hormogenice).

DIIODOTIROZINA (DIT) HO Tyr CH2CHCOOH- TIREOGLOBULINA

NH2
I
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 SINTEZA HORMONILOR TIROIDIENI 2 CUPLAREA IODOTIROZINELOR
I I I II

5 5
HO Tyr
CH2CHCOO
H + HO Tyr CH2CHCOOH
HO Tyr O Tyr CH2CHCOOH

NH2 NH2 3 3 NH2

I I I I
Tireoglobulina Tireoglobulina

3,5,35-tetraiodotironina
Cuplarea iodotirozinelor conduce la pierderea likajului
Peptidic la tiroeglobulina permitindu-se astfel trecerea T4
T# si T4 prin membrana celulara.
I 3,5,3-Triiodotironina

CH2CHCOOH
CH2CHCOO

NH2
HO Tyr HO
H Tyr CH2CHCOOH

NH2 + NH2 HO Tyr O Tyr

I I

Tireoglobulina Tireoglobulina I T3 I

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 Tireoglobulina
Glicoproteina
8-10% glucide
Resturi de tirozina
Sint. In cel tiroidiene, glicozilare, secretie in
coloid

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 Transportori
TBG (T4-70%)
Albumina (af mica, cap mare de legare
10%T4 si 30%T3)
TBPA (doar T4)

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 HORMONII TIROIDIENI-activitate
biologica, metabolism
POTENTA CONCENTRATIE LEGARE
HORMON RELATIVA PRODUCERE PLASMATICA LA PROTEINE t
PLASMATICE
(g/zi) (g/dL) (zile)
(%)

T4 + 80- 90 8 6-7
99.95

T3 ++++ 4-8 (24)* 0.3 99.7 1-3

rT3 - 2-3 (27) * 0.04 99.8 0.1

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* Valorile in paranteze arata converisa periferica
 3,5,35-tetraiodotironina

I I
DEIODURAREA

HO Tyr O Tyr CH2CHCOOH

NH2

I I
CALEA INACTIVARII T4 CALEA ACTIVARII

5-deiodinare 5- deiodinare

SELENODEIODINAZE
rT3
I I I T3 I

HO Tyr O Tyr CH2CHCOOH HO Tyr O CH2CHCOO

Tyr
H
NH2 NH2
I
I

3,3,5-Triiodotironina (revers T3) 3,5,3-Triiodotironina (T3)

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 SINTEZA I SECRETIA HH. TIROIDIENI
ENDOCYTOSIS OF
IODINATION OF THYROGLOBULIN BY
4 COLLOID IN FOLLICLE BY
THYROID PEROXIDASE PSEUDOPOD

TG
3 TG
TG
I

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FUSION OF PHAGOSOME
TG WITH LYSOSOMES

TG 6
DEGRADATION DEGRADATION OF
AND THYROGLOBULIN
RECYCLING
OF MIT/DIT 7
BY DEIODINASES FREE THYROXINE RELEASED FROM
T4
PROTEIN INTO CYTOPLASM

Other monovalent 2 8
anions compete IODIDE UPTAKE DIFFUSION OF THYROXINE
with iodide for BY Na/I THROUGH CELL MEMBRANE
uptake; sometimes SYMPORTER
with useful medical T4> > > T3
and experimental
applications e.g.
TCO 4;Cl0 4; SCN;
IODIDE IN Additional metabolism??
1 ECF~20nM 13
Reglarea secretiei T3/T4

-raport T3/T4 redus stimuleaz

secretie TRH care determina
secretie de TSH.

- Raport T3/T4 crescut exercita

feedback negativ pe secretia de
TRH si TSH .
Normal :
T4: 5-12 g/dl
T3: 80-180 ng/dl
TSH: 0.5-6 U/ml
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 Autoreglare
Prin mentinerea starii de eutiroidie,
independent de TSH
Prin nivelul concentratiei de iod
Iod scazut:

Stimularea sintezei de T3

Stimulata captarea iodului in tiroida

Iod crescut:

scade viteza de organificare a I-

In inanitie: stimularea transf T4 in rT3 (dim

arderile si consumul energetic)
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 Overview of sites of thyroid hormone regulation of metabolism.

Rashmi Mullur et al. Physiol Rev 2014;94:355-382

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2014 by American Physiological Society
 Actiuni fiziologice ale T3/T4

- stimuleaz creterea majoritii celulelor, mai ales

SN i oase (via activarea genelor GH i NGF)
- metabolice: cresc viteza metabolismului bazal,
metabolismul oxidativ, arderile i producerea de ATP,
aciune calorigen, cresc metabolismul proteic
- crete fracia de ejecie cardiac prin amplificarea
putreii contractiilor cardiace,
-stimuleaz metabolismul colesterolului i formarea de
acizi biliari
-stimuleaz expresia receptorilor LDL in hepatocite

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 Hipertiroidism
Medicamente care inhib producerea/secretia hh tiroidieni
(metimazol, propiltiouracil (PTU):
-Inhiba organificarea iodului
-Inhiba cuplarea MIT

Iod radioactiv [135I]

- Doar cel tiroidiene pot incorpora iod
- [135I] emite radiatii gamma () care distrug direct celulele tiroidiene
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