Lecture 5: The Thyroid Gland Flashcards
name the two physiologically active forms of thyroid hormones
T3 (triiodothyronine) and T4 (thyroxine)
what are the two cells types of present within the thyroid gland and what is their function?
- C (clear) cells which secrete calcitonin (Ca2+ regulating hormone).
- follicular cells which support thyroid hormone synthesis and surround hollow follicles.
describe thyroid follicles
- spherical structures whose walls are made of follicular cells.
- centre of follicle filled with colloid = sticky glycoprotein marix > contains 2-3 months supply of TH.
function of follicular cells
- manufacture the enzymes that make thyroid hormones as well as thyroglobulin, a large protein rich in tyrosine residues.
- also actively concentrate iodide from the plasma and transport it to colloid where it combines with the tyrosine residues to form the thyroid hormones.
- both tyrosine and iodide are derived from the diet.
how is iodide transported through the thyroid gland?
- iodide enters the follicular cells from the plasma via Na+/I- transporter (symport). The coupling to Na+ enables the follicular cells to take up iodide against a conc. gradient.
- iodide is then transported into the colloid via pendrin transporter.
action of thyroid peroxidase (aka thyroperoxidase)?
- catalyses the oxidation of iodide to iodine and the addition of iodine to tyrosine residues on the thyroglobulin molecule to create thyroid hormone.
addition of one iodine to tyrosine creates
MIT (monoiodotyrosine)
adding a second iodine to tyrosine resides on thyroglobulin molecule creates
DIT (diiodotyrosine)
conjugation of MIT + DIT =
T3 (triiodothyronine)
conjugation of DIT + DIT =
T4 (thyroxine)
what does TSH activate?
- in response to TSH, portions of the colloid are taken back up within the follicular cell by endocytosis.
- within the cells they are packages into vesicles containing proteolytic enzymes that cut the thyroglobulin to release thyroid hormones.
are T3 and T4 lipid or water soluble?
lipid soluble
how do T3 and T4 travel through the blood?
bound to plasma proteins, mainly thyroxine-binding globulin
does TBG have a higher affinity for T3 or T4?
T4, partly accounts for longer half-life
what % of plasma thyroid hormone is unbound (free)?
0.2%
- ONLY free hormone exerts an inhibitor effect on TSH and TRH and is physiologically active.
most TH circulates in the form of protein bound T3 or T4?
T4
90% of TH binding to TH receptors inside cells is T3 or T4?
T3 > TH receptor has a much higher affinity than T4 making it 3-5 times more physiologically active than T4.
which is more physiologically active: T3 or T4?
T3 >TH receptor has a much higher affinity for T3 than T4 making it 3-5 times more physiologically active than T4.
what factors stimulate increased TRH secretion from hypothalamus?
there is always a tonic release
cold
exercise
pregnancy
how are glucocorticoids and somatostatin inhibitory to thyroid hormone release
- SS inhibits TSH (TH required for HG action)
- GC inhibits TSH and conversion of T4 to T3.
thyroid hormone function
- raises metabolic rate and promotes thermogenesis, typically through promoting futile cycles of simultaneous catabolism and anabolism.
- increases hepatic gluconeogenesis
- net increase in proteolysis
- net increase in lipolysis
- critical for growth (stimulates GH receptor expression)
- essential for brain development in utero
describe Grave’s disease
- a common cause of hyperthyroidism.
- antibodies produces that bind and mimic TSH > continuous activation of thyroid gland.
- increased release of TH switches off TSH release from anterior pituitary so [TSH plasma] very low.
- thyroid gland may be 2-3x normal size due to hyperplasia.
- hyperactivity of cells also apparent.
describe a thyroid adenoma
- a rare cause of hyperthyroidism
- hormone-secreting thyroid tumour
symptoms of hyperthyroidism
- increased metabolic rate and heat production > weight loss/heat intolerance
- increased protein catabolism > muscle weakness/weight loss
- altered nervous system function > hyperexcitable reflexes and psychological disturbances e.g. anxiety
- elevated CV function (TH is permissive to epinephrine, beta receptors) > increased HR/contractile force, high output, cardiac failure
causes of hypothyroidism
- Hashimoto’s disease - autoimmune attack of thyroid gland
- deficiency in dietary iodine
- idiopathic
symptoms of hypothyroidism
- decreased metabolic rate and heat production > weight gain/cold intolerance
- disrupted protein synthesis > brittle nails/thin skin
- altered nervous system function > slow speech/reflexes, fatigue
- reduced CV function > slow heart rate/weaker pulse
describe goitre
- both hypo- and hyperthyroidism can result in hypertrophy of thyroid gland, termed goitre.
- may be caused by increased trophic action of TSH on thyroid follicular cells (hypothyroidism) or over-activity as a result of autoimmune disease (Graves disease)