Lect 16, thyroid Flashcards
thyroid hormones are derived from what amino acid? What element is required?
- tyrosine
- iodine is required
what cells in the thyroid gland are the site of synthesis?
follicular cell
Where is thyroid gland located
- below larynx, over the trachea
Where, in the thyroid gland, are hormones stored
- thyroid gland comprised numerous follicles which are filled with colloid and lined by follicular cells
- hormones are stored in the colloid of the lumen
what is the major protein of the thyroid colloid
thyroglobulin
what is the first step in thyroid hormone synthesis
- uptake (trapping) of iodide
- iodide trap: Na+/I- co-transporter
activity of the iodide trap is modulated by
diet, low iodide diet -> increased trap activity to compensate for deficiency
What is second step of thyroid hormone synthesis, after iodide trapping
- once iodide is inside cell, iodide is transported to the follicular lumen by pendrin
- iodide is then oxidized to iodine by thyroid peroxidase
what happens to iodine in the follicular lumen (colloid): step 3
- iodine attaches to a tyrosine on thyroglobulin
in the colloid, two coupling reactions occur, name them
- 2 DITs yield thyroxine (T4)
- 1 MIT and 1 DIT yields triiodothyronine (T3)
- reaction catalyzed by thyroid peroxidase
which thyroid hormone is produced more
more T4 is produced because the DIT + DIT coupling reaction is faster
do all the MITs and DITs couple?
no, portions of MIT and DIT do not couple but remain attached to thyroglobulin
how are thyroid hormones secreted from the colloid
- follicular cell engulf part of colloid containing thyroglobulin
- facilitated by megalin
- lysosomes attack colloid and proteases split iodinated products from thyroglobulin
- T3 and T4 diffuse into blood
in the follicular cell, once T3 and T4 are spit from MIT and DIT, what happens to MIT and DIT
they are deioninated by thyroid deiodinase
Name three reasons why T3 is more biologically active
- T4 binds more tightly to plasma proteins
- peripheral conceversion of T4
- thyroid hormone receptors in the nuclear have a greater affinity to T3
What happens to T4 when it enters a target cell
most of it is converted to T3, so cytoplasmic levels of T4 and T3 are about equal
binding of T3 or T4 to thyroid hormone receptors has what effect
bound thyroid hormone receptors bind to nuclear DNA, thus T3, T4 regulates transcription of genes
regulation of thyroid hormone secretion
- hypothalamus releases TRH : thyrotropin releasing hormone which acts on
- Thyrotoph cell isn anterior pituitary to release TSH: thyroid stimulating hormone
what two roles does thyroid stimulating hormone have
- acts on thyroid to stimulate secretion of thyroid hormones
- growth of thyroid gland
describe role of T3 in negative feedback loop regulation of thyroid hormones
- inhibits release of TSH by down regulating TRH receptor on thyrotrophs and decreasing TSH synthesis
- inhibit release of TRH in the hypothalamus
what is the key hormone in negative feedback loop regulation of thyroid hormones
T3
role of somatostatin and dopamine in thyroid hormone regulation
- somatostatin and dopamine, released by hypothalamus, inhibits TSH release
TRH from hypothalamus utilizes what protein receptor mechanism on thyrotrophs
- TRH binds to G protein coupled receptor
- raising Ca2+
- cause thyrotrophs to synthesize and release TSH
describe effects of thyroid hormones on metabolism
- increase metabolic rate
- increase oxygen consumption
- increase body temperature
describe how hyperthyroidism promotoes futile cycles in BMR, Carb metabolism, protein metabolism, and lipid metabolism
- causes increased synthesis and degredation of carbs, protein, and lipids
- causes net degradation of tissue protein -> can lead to a loss of muscle mass
physiological effects of thyroid hormones on CV system
- increase CO and ventilation
- T3: chronotropic and inotropic, and reduces vascular resistance
physiological effects of thyroid hormones on sympathetic nervous system
- increases synthesis of B adrenergic receptors in cardiac, skeletal muscles and adipocytes
- no change in catecholamines
- contributes to thermogenic response
why is normal/high thyroid levels important in pregnancy
- thyroid hormone is essential for normal maturation of CNS
- low thyroid status during development is detrimental
physiological effects of thyroid hormones on growth
- required for normal growth and development
- promotes bone formation
cretinism
- condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones (congential hypothyroidism)
- due to maternal nutritional deficiency of iodine
how is a goiter formed
- iodine deficiency
- thyroid cant produce hormone to maintain feedback mechanism
- pituitary responds by secreting more TSH which stimulates growth of thyroid gland
- -> hypothyroidism and goiter (large thyroid)
what is hashimotos thyroiditis
- antithyroid antibodies destroy thyroid gland function
- early stages: elevated TSH but normal T3 and T4
- if untreated: see gradual decline of T3, T4
what is Graves disease
- hyperthyroidism
- antibodies mimic TSH and bind to TSH receptors on the thyroid
- stimulates thyroid hormone production
- get loss of feedback control
exophthalmos is a common sign of
graves disease: hyperthyroidism
function of 5’/3’ monodeiodinase
involved in peripheral conversion: removes iodine from T4 -> T3
differentiate between type I and II peripheral conversion
- type I: liver, kidney, thyroid
- type II: pituitary, CNS, placenta
when is type I peripheral conversion reduced
caloric restriction and severe stress
- *conversion of T4->T3 at liver, kidneys, thyroid is reduced
- these tissues become unresponsive to thyroid hormone = decreased metabolic rate
