Normal anatomi: Thyreoidea - uio.no · produserer kalsitonin Normal thyreoidea. 2 Fysiologi...
Transcript of Normal anatomi: Thyreoidea - uio.no · produserer kalsitonin Normal thyreoidea. 2 Fysiologi...
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Thyreoidea (skjoldbruskkjertelen) Anatomi og fysiologi
A. Rustan FRM3020 2006
Glandula thyreoidea Normal anatomi:
• Høyre og venstre lapp, 2x4x6 cm,vekt 20-25 gram, med rødbrun,kapselbekledt overflate, lobulertog glinsende
Normal histologi:• Består av tettliggende follikler
bekledt med kubisk epitel somproduserer thyroglobulin
• Parafollikulære c-cellerproduserer kalsitonin
Normal thyreoidea
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Fysiologi
Thyreoidea Thyroidhormoner
Tyroksin, T4
Trijodtyronin, T3
(Calcitonin)
Syntese/lagring/sekresjon TRH → TSH → T3/T4 Opptak av jod Oksydasjon og jodinering av tyroglobulin Endocytose og sekresjon
Regulering Stimulerende: TSH (tyrotropin) Hemmende: Somatostatin Negativ ”feedback” (T3/T4) Fysiologisk
Thyreoideahormoner Effekter
Metabolske: Kalorigen effekt, regulerer energiomsetningen ogvarmeproduksjonen (BMR=basal metabolic rate)
• Egeneffekt• Via andre hormoner• Stimulerer syntese av β-reseptorer
Vekst og utvikling Cellulære virkningsmekanismer
T3-R Direkte effekt på mitokondrier (UCP),
Transport og metabolisme Høy proteinbinding (TBG) Konvertering T4 → T3
Sykdommer Hypertyreose/tyrotoksikose Hypotyreose Struma
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T4 → T3
T4 → T3
PKAactivation
PROTEINPHOSPHORYLATION
Cell GrowthSecretion of Thyroid
HormoneT4
Hypothalamus
The TRH-TSH- T4 axis
↓ TRH
↓ sensitivity to TRH
Thyroid
Thyrotroph (via IP3/Ca2+
and DAG)
TRHTSH
FSH
LH
hCG
βFSHα
βLHα
βTSHα
PlacentaβCGα
Pituitary
TSH
ATP cAMPAdenylylCyclase
II
CH2CH-COOH
NH2
O
I I
HO
3,5,3',5'-Tetraiodothyronine (T4)most abundant form
Inactivation infasting adult
5-deiodinaseCH2CH-COOH
NH2
O
I
I I
HO
3,3',5'-Triiodothyronine (reverse) (rT3)inactive form
5'-deiodinase
Activation infed adult
Peripheraltargettissue
3,5,5'-Triiodothyronine (T3)most potent form
CH2CH-COOH
NH2
O
I
I I
HO
Chemistry and interconversions of the thyroid hormones
CH2CH-COOH
NH2I
I
HO
3,5-Diiodotyrosine (DIT)
CH2CH-COOH
NH2
I
HO
3-Monoiodotyrosine (MIT)
Structures of MIT and DIT
Precursors that when coupled together form thyroid hormonesDIT + DIT = T4 MIT + DIT = T3
IODINETrace elementThyroid gland concentrates iodine – contains 90% of body poolIodine transported and taken up as iodide ion
SecondaryLysosomes
Iodination
Peroxidase Peroxidase
DITTgb
DIT
DITDIT
DITMIT
MITMIT
MIT
Tgb
Tgb
I-
I+
Coupling
DITTgb
DIT
DITMIT
T3 MIT
DITT4
T4
TSHSecretion
TRH
Adenylylcyclase
TSH ReceptorSymport
*
I-
I-Na+
Na+
TgbTyr Tyr
Extracellular Space (COLLOID)
THYROID FOLLICULAR CELL
Oxidation/H2O2
Secreted to Colloid
TgbmRNA
TgbTyr
Tyr
Protein synthesis
Tyrosine + otheramino acids
T4,T3
MITDIT
Protease-Hydrolysis
Diffusion
T4,T3
Release
PKA
cAMP
Increasedcell growth
Lysosomes
Na+/K+-ATPase
K+
Na+
Extracellular Space (BLOOD SIDE)
Iodine metabolism in the thyroid follicle and its stimulation by TSH
Mitochondrion
H2O2
O2 + H+
NADPHNADP+
Concentration
Deiodination
Thyroid-specificdeiodinase
LATS/TSI
Tgb* * *
*
TSH
Peroxidase
Peroxidase
PeroxidaseIn Golgi
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Thyroid Target Cell(e.g., pituitary/brain, liver, muscle, heart)
T3 receptorRNA Pol
Nucleus
Inducedgene
Responseelement
New Proteins(enzymes)
mRNA
Trans-crip-tion
Translation
Circulating T4 - bound to TBG or TBPA
G3PDH
UCP
Mitochondria
deiodinationT3 T4 5' deiodinase
RXR T3 Na+,K+-ATPase
Temp homeostasis:heat generation fromATP used by Na,K-ATPase in liver andother tissues.“Futile cyclus”
O2
↑ O2 consumption↑ BMR
Action of the thyroid hormones
Other effects of T3:↑ brain development, myelination↑ Growth (GH transcribed in somatotrope; induction of anabolic enzymes)↓ TSH in thyrotrope (repressive pituitary effect)↑ β1-adrenergic receptor
RXR T3RXR T3RXR T3
T3/T4-syntese
T3/T4-signalering