Unit 3.2 Day 22 Learning Objectives

Thyroid axis

hypothalamus

TSH - || + TRH

pituitary

| + TSH

thyroid

| T4 T3

targ. tiss. (liver, auditory, skele., brain, bone, heart)

thyroid hormone synthesis oreintation

follicle cell: apical and basal sides

colloid

thyroid hormone synthesis overview of TG→T4 process

in follicle cell, thyroglobulin (TG) synth. + secretion

in colloid, thyroglobulin is iodinated into iodothyroglobulin to store

brought back into follicle cell

processed into T4

diffuses out of cell

thyroglobulin (TG) characteristics

large precursor

• 6.4 × 10^5 daltons

• 8% CHO by mass

  • attached to aspartic acid residues

• homotetrameric (4 subunits): 1.6 × 10^5 Daltons ea. subunit

• 130 tyrosines/subunit

  • easily iodinated w/ 1 or 3 iodines

• 1 thyroglobulin produces 2 T4 molecules

role of iodine

enters/exits follicle cell via. transport proteins

added to tyrosine (Y) residues on thyroglobulin (TG) turning it into iodothyroglobulin

T3/T4 structure

4 I = T4 (more abundant), thyroxine, tetraiodothyronine

3 I = T3 (more bioactive), triiodothyronine

detailed TG → T4 process

1. thyroglobulin (TG) synth. via gene expression in follicle cell

2. thyroglobulin secreted (exocytosis) at apical side of follicle cell into colloid (follicular space)

3. in colloid, thyroglobulin is iodinated into iodothyroglobulin to store

4. upon stim. iodothyroglobulin is endocytose back into follicle cell (at apical side)

5. lysosome processes iodothyroglobulin into thyroxine (T4)

6. T4 diffuses out of membrane at basal side to capillaries

detailed role of iodine

1. iodine enters follicle cell through NA/I symporter

2. iodine transverses the follicle cell

3. iodine leaves apical side of follicle cell via membrane protein

4. in colloid, iodine oxidized + added to tyrosine (Y) residues on thyroglobulin (TG) turning into iodothyroglobulin

5. 2 iodinated Y residues conjugate together

6. 1 is cleaved from TG precursor

7. iodinated TG is endocytose back into follicle cell

8. triiodothyronine (T3) + T4 cleaved from TG + diffuse into capillaries

thyroid hormone regulation: endocrine control

endocrine axis

negative feedback loops

• 3 long loop

• 2 short loop

thyroid hormone regulation: nervous control

via vagus nerve

• ACh → thyroglobulin

• EP +/- → thyroid

thyroid hormone regulation: paracrine

TSH → mast cells → 5HT → follicle cells

products + conversions

75-80% of TH released from thyroid is T4

under 5% is rT3

15-20% is T3

once inside target tissues, cells primarily convert T4 into T3

T3 is primary bioactive compound

T4 may play a role n negative feedback

TH mechanism of action

hypothalamus

| TRH

a. pituitary

| TSH (neg. to hypothal)

thyroid (ACh + EP -/+ act on thyroid)

| mast → 5HT → T3/4

| T4, T3

target tissues (T4)