Thyroid Endocrinology: Anatomy, production of T3 & T4, function of thyroid & thyroxine

which hormone has a higher conc. in the blood? which is the major hormone of the thyroid?

T4 T3 because T4 is converted to T3 (T4 can be thought of as a reservoir for additional T3)

metabolic actions of T3

OVERALL INCREASES METABOLISM stimulates carb absorptions from small intestine increases fatty acid release from adipocytes provides energy to maintain metabolism at high rate much of that energy is used to *support Na+/K+ATPases* throughout the body activity of Na+/K+ATPases produces heat = *temperature homeostasis*

Permissive actions of T3:

Up regulates beta-adrenergic receptors in many tissues therefore over active thyroid with excess T3 causes symptoms similar to excess adrenaline = racing heart, anxiety, nervousness

what is colloid?

a protein rich material at the core of follicular cells in the thyroid

embryology of the thyroid gland:

appear at 3-4 weeks as an epithelial proliferation at the base of the pharynx migrate down the thyroglossal duct to below the larynx begin producing thyroxine at 18-20 weeks

follicles of the thyroid:

centre contains thyroglobulin in which iodine is stored and taken up from the blood

3 primary features of the histology of the thyroid gland

follicle follicular cells parafollicular cells/C cells

how is T3 involved in development during fetal life?

formation of axon terminals production of synapses growth of dendrites and dendritic extensions formation of myelin

How and where is T4 converted to T3?

in target cells by enzymes called deiodinases

how does T3 act?

induces gene transcription and protein synthesis

what is the control mechanism of thyroid stimulating hormone?

negative feedback action of T3 and T4 on the anterior pituitary gland and (to a lesser extent) on the hypothalamus

what causes hypertrophy of thyroid cells

overexposure to greater conc. of TSH causes increase in size (goiter)

where can you find receptors for thyroid hormone?

present in the nuclei of most cells in the body = widespread distribution

Parafollicular cells of the thyroid:

produce calicitonin for Ca2+ homeostasis

T3 is also required for

proper nerve and muscle reflexes and normal cognition in adults

how is T3 involved in growth and development?

required for normal production of growth hormone from anterior pituitary

follicular cells of the thyroid:

simple cuboidal epithelium becomes columnar with increased metabolic activity arranged into hollow spheres called follicles produces hormones T3 & T4

Functions/roles of TSH

stimulates all actions of the follicular epithelial cells increases protein synthesis in follicular cells increases DNA replication and cell division increases amount of RER and other cellular machinery required by follicular cells for protein synthesis

Thyroid is innervated by branches of the

sympathetic trunk

what controls hormone release from the thyroid

the pituitary gand

How are thyroid hormones produced in the absence of dietary iodine?

there is sufficient iodinated thyroglobulin stored within follicles of the thyroid to provide thyroid hormone for several weeks even in the absence of dietary iodine - very unique!

Control of thyroid function: what stimulates the actions of the follicular epithelial cells?

thyroid stimulating hormone which is stimulated by thyroid releasing hormone

what is T4?

thyroxine - product of the thyroid gland, contains 3 iodines

what is T3?

triidothyronine - product of the thyroid gland, contains 3 iodines

Synthesis of thyroid hormones:

1. circulating iodine is actively transported with Na+ ions across the basolateral membranes of the follicular cells = iodine trapping 2. Na+ is then pumped back out via Na+/K+-ATPases 3. Negatively charged iodide ions diffuse towards the apical membrane of the follicular cells and are transported into the colloid 4. colloid contains a large amount of the protein thyroglobulin 5. iodide is rapidly oxidised to iodine and binds to tyrosine residues on the thyroglobulin molecules under the action of the enzyme thyroid peroxidase 6. tyrosine binds to one iodine molecule = monoiodotyrosine T1 OR binds to two iodine molecules = diiodotyrosine T2 7. Thyroid is stimulated to produce thyroid hormone 8. T1 and T2 are cleaved from their tyrosine backbone and join to create T3 (still attached to thyroglobulin tho) 9. extensions of the colloid-facing membranes of the follicular cells engulf portions of the colloid by endocytosis 10. brings the iodated thyroglobulin into contact with lysosomes in the cell interior 11. proteolysis results in release of T3 and T4 which are able to diffuse out of follicular cells into the interstitial fluid and then the blood