Thyroid Hormones and Energy Homeostasis

Question 1

Explain where the thyroid is and its structure.

Answer 1

Below the larynx and composed of follicles. Follicles composed of epithelial cells which surround a proteinaceous colloid - where the thyroid hormones are stored. Can grow/shrink depending on demand!

Question 2

Explain the 2 thyroid hormones.

Answer 2

T4 = thyroxine.
T3 = tri-iodothyronine - 10x more potent.

T4 converted to T3 at target tissue.

99% of T4 is in plasma bound to thyroid binding globulin (TBG). 1% = free = active.

Question 3

Explain the production of thyroid hormones.

Answer 3

Iodide from the diet enters via secondary active transport. Oxidised by thyroid peroxidase. (Thyroglobulin is synthesised in follicular cells). Tyrosine AA are iodinated within thyroglobulin. In Colloid, 2 tyr AA join to form T3 and T4 attached to thyroglobulin. Thyroglobulin is endocytosed into follicle. Release AA to be reycyled and T3 and T4 to circulation.

Question 4

Explain stimulation of thyroid hormone release.

Answer 4

Thyrotropin releasing hormone (hypothalamus) –> Thyroid stimulating hormone (AP) –> T3 and T4 –> target cells.

T3 provides negative feedback to AP and hypothalamus.

TSH stimulates growth of thyroid.

Question 5

In brief, what are the main actions of thyroid hormones?

Answer 5

Absolute requirement for growth and development.
Increased O2 consumption in most tissues.
- sets MBR and regulates Tc.
Central effects.

Question 6

What happens in the absence of thyroid hormones?

Answer 6

Growth retardation, underdeveloped CNS, axonal retardation = mental retardation.
T3/T4 have some permissive effects on other hormones - GH, IGF.

Question 7

Explain how thyroid hormones set BMR.

Answer 7

Increase mitochondrial oxidative phosphorylation.
Regulate expression of enzymes involved in metabolic processes.
Increase plasma Na/K ATPase activity - increase NS excitability.
Regulate seasonal changes in body weight.

Question 8

Explain how thyroid hormones regulate body temperature.

Answer 8

Uncouple ATP synthesis from metabolism - increase expression of UCP-1 = heat production.
Direct effects on mitochondria of brown adipose and skeletal tissue.e

Question 9

Explain the central effects of T3/4

Answer 9

Stimulate sympathetic outflow to brown fat (thermeogenesis) and kiver (gluconeogensis and catabolism).
Increase food intake.
Regulated body weight.

Question 10

Thyroid failure?

Answer 10

Congenital = from birth, severe developmental abnormalities = cretinism.
Acquired later in life - dietary deficiency - dietary supplementation.

Question 11

Hypothyroidism?

Answer 11

Low metabolic rate.
Weight gain.
Cold sensitivity.
Deficient growth.
Slow mental processes.
Decrease cardiac activity

Lack of T3/4 = lack of -ve feedback therefore increase TSH - growth of thyroid - non toxic goitre.

Question 12

Hyperthryoidism.

Answer 12

Graves disease.

Autoimmune disease - antibodies that stimulate T3/T4 release - mimic TSH.

High BMR.
Wight loss.
Heat sensitivity.
Hyperactive NS, tremor, anxiety.
Increased cardiac activity.

Thyroid growth - toxic goitre and exopathalamus.

Treatment - inhibit thyroid peroxidase and surgically remove goitre.