Thyroid Hormones

Question 1

Hypothalamic TRH > Pituitary TSH > Thyroid gland produces thyroxin (T₄) and triiodothyronine (T₃)

Both T₄ and T₃ have the effect of _____, adjusted to alteration in ____, ___, ___, ___

Answer 1

T₄ & T₃ increase O₂ consumption & metabolism

Adjusted in alteration in heat production, energy need, caloric supply, and environmental temperature

Question 2

Describe the structure of a follicle.

Answer 2

Cuboidal endocrine cells surrounded by basement membrane forms single-layered circular follicles, the lumina of which contain thyroid hormones stored as colloid material

Question 3

Thyroid gland also contains ___ that secrete ___.

Answer 3

parafollicular / C - cells

Secretes calcitonin

Question 4

The stimulation of thyroid by ___ causes follicular cells to become more active at what?

Answer 4

TSH –> follicular cells become more active at

• Iodine uptake
• TH production

Question 5

Iodothyronines

Answer 5

Secretory products of the thyroid glands

Iodine incorporated into 2 tyrosines

Question 6

The major secretory product / iodothyronine of thyroid glands is ___, also known as ___.

Answer 6

3, 5, 3, 5 tetraiodothyronine AKA thyroxin (T₄)

Functions largely as a circulating prohormone

Question 7

The minor iodothyronine secreted is ___ AKA ___, which functions to ___

Answer 7

3, 5, 3 triiodothyronine AKA triiodothyronine (T₃)

Provides almsot all thyroid hormone activity in target cells; produced in various tissues from the circulating prohormone T₄

Question 8

When less thyrhoid hormone action is needed, what happens to prohormone T₄?

Answer 8

It’s turned into revers T₃ (rT₃), which is inactive and has unknown hormonal action

Question 9

Thyroid hormone synthesis steps

Answer 9

1. UPTAKE AND CONC OF IODIDE in the gland
   
   1. Actively transported via Na-I cotransporter
   2. Iodide trap: process that maintains [iodide]_gland >> [iodide]_plasma
2. OXIDATION & INCORPORATION OF IODIDE
   
   1. Thyroid peroxidase incorporates iodide in Tyr of thyroglobulin –> monoiodotyrosine (MIT) and diodotyrosine (DIT)
3. COUPLING OF 2 IODINATED TYROSINES
   
   1. Thyroid peroxidase couples
      
      1. two DITs –> T₄
      2. MIT + DIT –> T₃
   2. T₄:T₃ is usually 10:1, but restricted iodide availability leads to increased T₃ formation

Question 10

Thyroid peroxidase

Answer 10

Uses H₂O₂ to oxidize iodine

Iodinates the tyrosines on thyroglobulin (protein w the Tyrs)

Question 11

Thyroid hormones within ___ are cleaved by ____ and go through the basement membrane to enter the capillary blood.

Answer 11

Thyroglobulin cleaved by lysosomal enzymes to release T₃ & T₄, which will go through the basement membrane, leave the cells and enter into the capillary blood.

Question 12

Deiodinase

Answer 12

The MIT and DIT molecules are rapidly deiodinated by enzyme deiodinase and iodide is reutilized for new hormone synthesis.

Question 13

Where are iodinated thyroglobulins store?

How do they get transferred into endocrine cells?

Do they leave the endocrine cell?

Answer 13

Stored as colloid in follicle

Transferred from lumen of follicle into endocrine cells by endocytosis, but intact thyroglobulin doesn’t leave the cell.

Question 14

Wha treactions occur within the endocrine cell?

Answer 14

Iodide traps

Thyroglobin synthesis

Question 15

What reactions occur at the interface between the cell membrane and the colloid?

Answer 15

Iodination rxn

Coupling rxn

Question 16

What reactions occur after thyroglobulin’s reabsorption from the colloid?

Answer 16

Cleavage by lysosomal enzymes to release T₃ & T₄

–> secretion of T₃ & T₄

Question 17

Thiouracil drugs

Answer 17

Blocks enzyme peroxidase to treat thyroid hyperfunction

Question 18

Iodide itself can be used to treat ___thyroidism

Answer 18

hyperthyroidism

Question 19

Negative feedback of thyroid hormones

Answer 19

T₄ & T₃ inhibit synthesis of both TSH & TRH

T₃ block TRH’s effect and suppresses its release

Question 20

TRH or TSH:

Which is a tripeptide?

Which is a glycoprotein?

Answer 20

TRH = tripeptide

TSH = glycoprotein composed of two peptide subunits

Question 21

Synthesis & action of TRH

Answer 21

Cut from a precursor tetrapeptide to a tripeptide TRH

1. TRH binds its own receptor
2. Increases in Ca2+ and IP3 –> stimulate release of TSH from anterior pituitary
3. Downregualtes/desensitizes its own receptor

Question 22

TSH / Thyrotropin functions

Answer 22

Stimulates all aspects of metabolism & growth of thyroid cells as well as

• iodide trapping
• thyroid hormone synthesis & secretion
• colloidal endocytosis

Question 23

Iodide deficiency has what impact on TSH secretion?

Answer 23

Increases TSH secretion because thyroid hormone isn’t being synthesized

Question 24

Goiter

Answer 24

enlarged thyroid gland due to TSH hypersecretion

Ex) from iodide deficiency -> cant make thyroid hormone ->increase TSH

Question 25

What **inhibits TSH secretion**?

Answer 25

* **T₃ **suppresses TSH release; represses TSH gene expression; downregulates TSH receptors * **Dopamine** * **Somatostatin** * **Cortisol** * **Growth hormone**

Question 26

T₄ and T₃ are bound to what proteins while circulating?

Answer 26

* **Thyroxin-binding globulin (TBG)** binds ~20% of T₄ and T₃ * **Transthyretin (thryoxin-binding parvalbumin**) * **albumin**

Question 27

The \_\_rity of total T₄ and T₃ are in the free state

Answer 27

MINORITY

Question 28

What is the function of **TBG & transthyretin?**

Answer 28

To create a circulating reservoir of T₄ --\> provides buffering capacity against cute changes in thyroid gland function

Question 29

Sustianed changes in the daily T₄ supply from thyroid disease can lead to

Answer 29

sustained changes in both the bound and free reactions

Question 30

Acute hepatic disease, pregnancies, estrogen therapy, or kidney disease can change ___ levels, which will disturb the ratio of free to bound T₄

Answer 30

**serum TBG level**

Question 31

Thyroid hormone replacement therapy is carried out with which thyrhoid hormone?

Answer 31

**T₄** (less hormonally active, but can be converted to T₃ or rT₃)

Question 32

5 monodeiodinase

Answer 32

T₄ --\> T₃

Question 33

major target tissues of thyroid hormone

Answer 33

liver kidney skeletal muscle

Question 34

T₄ and T₃ enter target cells by ___ then

Answer 34

energy-depenent transport Then most of the T₄ is converted to T₃ and both T₄&T₃ are transported to the nucleus to affect transcription. T₃ binds nuclear receptors w greater affinity

Question 35

Physiological effects of thyroid hormone

Answer 35

* **Increased basal metabolic rate & general catabolic state** * **Thermogenesis** * Increased **O₂ consumption** * Increases **kidney size, renal plasma flow, GFR,** and **tubule transport** * Increases cardiac **SV, HR, systolic BP** * **Decreased diastolic BP** * **CNS** **development** * Increased **skeletal growth** * Regulates **reproductive function**

Question 36

How does TH increase O₂ consumption?

Answer 36

Stimualtes Na,K-ATPase, so ADP increases --\> increased mitochondrial O2 uptake Rate of O₂ consumption can be used to classify hypo (150mL/min), euthyroid (250mL/min), and hyperthyroid states (400mL/min)

Question 37

Hyperthyroidism clinical features

Answer 37

Tx: B-adrenergic antagonists

Question 38

Thyroid hormone causes increased \_\_\_\_, which shortens diastole, thereby increasing heart rate

Answer 38

sarcolemal uptake of Ca²⁺ shortens idastole

Question 39

Causes of hyperthryoidism

Answer 39

**Graves**: autoimmune; antibody binds TSH receptors and mimics TSH **Neoplasm of thyroid** **Thyroid inflammation; Excess TSH, ingestion of excess T₃ & T₄ ; High iodide**

Question 40

Tx of hyper thyroidism

Answer 40

Short-term iodine excess Treatment with thiouracil for 18 months to block TH synthesis Ablation of thyroid tissues via radioactive iodine or surgery

Question 41

Hypothyroidism

Answer 41