2/14 Thyroid Core Concepts - Wondisford

Question 1

thyroid hormone precursors

Answer 1

thyronine nucleus → precursors (DIT, MIT) → secreted hormones

• T3 = DIT+MIT
• T4 = DIT+DIT

Question 2

thyroid gland breakdown

Answer 2

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

Question 3

thyroid hormone biosynthesis

“___-___-___)

Answer 3

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

Question 4

role of iodine graphic

Answer 4

Question 5

TSH signaling at thyroid follicular cell

Answer 5

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 →→→

1. TH secretion
2. thyroglobulin synthesis
3. thyroid growth
4. I trapping

Question 6

thyroglobulin

vs

thyroid binding globulin

Answer 6

thyroglobulin is backbone on which T4 and T3 are made in colloid of thyroid

TBG is protein in serum that binds thyroid hormones

Question 7

HTP axis

players

Answer 7

hypothalamus_paraventricular nucleus: TRH

ant pituitary_thyrotroph: TSH

thyroid: T4/T3

Question 8

thyroid hormone transport, levels

Answer 8

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

Question 9

thyroid hormone action

Answer 9

two potential actions via remove/replace of gene transc coactivator or corepressor

1. activate gene expression
   
   • myelin basic protein
   • Purkinje cell protein
   • a-MHC protein
   • Ca ATPase
2. inhibit gene expression
   
   • TSH subunit genes
   • TRH

Question 10

thyroid hormones

types of deiodinases

Answer 10

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

Question 11

source of thyroid hormone in serum

Answer 11

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

Question 12

iodine deficiency

Answer 12

iodine sufficiency

• TPO forms T4 exclusively
• T3 synth via D1 within thyroid, D1/D2 in periphery

iodine deficiency

• TPO forms both T4 and T3

Question 13

summary

Answer 13