2/14 Thyroid Core Concepts - Wondisford Flashcards
thyroid hormone precursors
thyronine nucleus → precursors (DIT, MIT) → secreted hormones
- T3 = DIT+MIT
- T4 = DIT+DIT
thyroid gland breakdown
thyroid composed of lobes composed of lobules composed of follicles composed of follicles composed of follicular cells attached via tight jx
why tight jx?
watertight to keep thyroglobulin (aka colloid) inside
thyroid hormone biosynthesis
“___-___-___)
out, in, out
raw material
- A. thyroglobulin synthesized, discharged into follicle lumen
- B. iodide is trapped in follicular cell by Na/I symporter
- C. iodide → iodine via H2O2 rxn
synthesis (in colloid) via thyroperoxidase
- D. iodine + Tyr (in colloid) → DIT, MIT
- E. iodinated Tyr linked together → T4, T3
packaging/release (in cells)
- F. thyroglobulin colloid endocytosed, combined with lysosome
- G. lysosomal enzymes cleave T4 and T3 from thyroglobulin colloid → T4, T3 diffuse into bloodstream
*there is obligate release of some amt of thyroglobulin (degraded) with T4, T3
- i.e. if you’re making thyroid hormones, you’ll see thyroglobulin. if you’re not making thyroid hormones, you wont see thyroglobulin
role of iodine graphic
TSH signaling at thyroid follicular cell
TSH is a heterodimeric glycoprotein hormone → TSHalpha + TSHbeta
- alpha subunit is common for all glycoproteins (FSH, LH, TSH, hCG)
- beta subunit is unique to TSH
- glycosylated
7pass transmembrane G-protein coupled receptor (Gs) activates adenylate cyclase → makes cAMP →→→
- TH secretion
- thyroglobulin synthesis
- thyroid growth
- I trapping
thyroglobulin
vs
thyroid binding globulin
thyroglobulin is backbone on which T4 and T3 are made in colloid of thyroid
TBG is protein in serum that binds thyroid hormones
HTP axis
players
hypothalamus_paraventricular nucleus: TRH
ant pituitary_thyrotroph: TSH
thyroid: T4/T3
thyroid hormone transport, levels
T4: prohormone
- 99.97bound/0.03free
- 75 TBG
- 15 TBPA
- 10 albumin
- amount vs affinity: high amount, low affinity
T3: hormone
- 99.7bound/0.3free
- 75 TBG
- 25 albumin
- amount vs affinity: low amount, high affinity
thyroid hormone action
two potential actions via remove/replace of gene transc coactivator or corepressor
- activate gene expression
- myelin basic protein
- Purkinje cell protein
- a-MHC protein
- Ca ATPase
- inhibit gene expression
- TSH subunit genes
- TRH
thyroid hormones
types of deiodinases
hormones
- T4 → active
- T3 (outer ring I removed) → active
- reverse T3 (inner ring I removed) → inactive
- T2 (outer ring and inner ring I removed) → inactive
deiodinases : T4 → __________
- type I (D1) : peripheral T3, rT3 (minor)
- type 2 (D2) : peripheral/intracellular T3
- type 3 (D3) : peripheral thyroid hormone INACTIVATION (major)
- takes off inner ring iodine
source of thyroid hormone in serum
thyroid typically only synthesizes T4
within thyroid, low level of D1 activity: minor T4→T3 conversion
major source of T3 : peripheral T4→T3 conversion (D1/D2)
inactivation: action of D3/D1
iodine deficiency
iodine sufficiency
- TPO forms T4 exclusively
- T3 synth via D1 within thyroid, D1/D2 in periphery
iodine deficiency
- TPO forms both T4 and T3
summary
