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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

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