Thyroid Gland and Thyroid Hormones Flashcards
The thyroid gland is located inferior to the ___, and is one of the largest endocrine glands. Each lobe is about ___cm long x ___cm wide, and weighs ~___g. The lobes are connected by an ___. The thyroid gland is highly ___.
larynx; 4; 2; 20; isthmus; vascular
What is the internal structure of the follicle?
it is formed by spheres of epithelial cells and filled with colloid
The ___ surface of the epithelial layer faces the colloid and the ___ surface faces the blood supply.
apical; basal
The epithelial cells are also called ___ cells and they regulate the production of two ___-containing hormones.
follicle; iodine
What does the lumen of the thyroid follicle contain?
thyroglobulin
T/F. Thyroid hormones are peptide hormones that are stored in secretory vesicles.
False, thyroid hormones are LIPOPHILIC, and, thus, cannot be stored in secretory vesicles.
Where is thyroid hormone synthesized and stored?
it is synthesized extracellularly in the colloid and stored there.
How is iodide transported across the basal side of the follicle cell?
via a Na+/I- transporter
How does intracellular iodide enter the colloid of the follicle?
it diffuses down its concentration gradient across the apical membrane
The follicle cells synthesize a large, ___-rich protein called ___ and the enzyme ___ ___. Both proteins are ___ across the apical membrane into the colloid.
tyrosine; thyroglobulin; thyroid peroxidase; exocytosed
T/F. The colloid is EXTRAcellular fluid.
True.
How is iodide oxidized? Why is this a critical step?
Iodide is oxidized by thyroid peroxidase and linked to thyroglobulin. Binding I- to TG maintains the concentration gradient needed to continuously sequester I- in the colloid.
If one I- is added to a ___ residue the resultant molecule is ___ but iodinating two sites produces ___.
tyrosine; monoiodotyrosine; diiodotyrosine
How is tetra-iodothyronine (T4, or thyroxine) formed? Tri-iodothyronine (T3)?
DITs combine with either other DITs to form T4 or and MIT to form T3
How is T3 and T4 stored?
attached to TG in the colloid
Why is T3 and T4 unable to diffuse out of the cell?
because it is attached to TG
What is the rate limiting step in thyroid hormone synthesis?
step 1. Iodide is transported across the basal side of the follicle cells via a Na+/I- transporter. This step depends on the availability of iodine in the environment/diet.
How is the secretion of thyroid hormone stimulated?
by TSH, which is released from the anterior pituitary in response to TRH from the hypothalamus
Where are TSH receptors located?
On the follicle cells. TSH also acts to increase synthetic activity of the follicle cells and stimulate hyperplasia
In response to ___, droplets of colloid containing TG + T3/T4 are ___ into the follicle cells. The droplet fuses with a ___ containing enzymes that ___ T3 and T4 from the TG.
TSH; pinocytosed; lysosome; cleave
T3 and T4 are released into the cytoplasm by lysosomal ___. They then diffuse into ___ and attach to binding proteins once inside the blood. List the three binding protiens they may bind.
hydrolysis; capillaries
Thyroid binding protein (TBP), Albumin, Prealbumin
How is new TG formed?
Amino acids from the degraded TG are recycled into new TG
Which form of thyroid hormone is secreted the most? Which form is more biologically active?
T4 (90%) is secreted the most but T3 (10%) is more active because it has a greater affinity to bind the receptor
What happens to the secreted T4?
Most (80%) is converted to T3 in the liver and kidney
When T4 is converted to T3, what happens to the extra iodide?
it is returned to the colloid.
Why is it important that more T4 is secreted and not converted to T3 until it enters circulation?
This maximizes the concentration gradient for free iodide between the blood (high) and colloid (low) and helps insure that iodide is available for thyroid hormone synthesis. Otherwise the iodide would get secreted from the body.
T/F. Receptors for TH are found on the membrane of cells.
False, they are found in the nuclei of most cells of the body.
How many different receptor types are there?
Four. The alpha and beta forms are encoded by 2 different genes and type 1 and 2 result from alternative splicing of the transcript
Expression of the receptor isoforms differs with respect to stage of development and target tissue. Give an example.
Alpha 1 is expressed during fetal development and Beta is expressed in neural tissue.
___ occupied by TH will ___ and form a DNA binding protein that regulates gene transcription.
Receptors; dimerize
What part of the TH receptor will stimulate or suppress expression?
The transactivation domain regulates the downstream transcription of proteins.
How do TH receptors inhibit transcription?
Unbound receptor dimers can also bind DNA and typically inhibit transcription.
What is the principle effect of TH?
to stimulate cellular metabolism
TH increases ___/___-___ activity and synthesis to regulate the rate at which cells burn fuel/make ATP.
Na+/K+-ATPase
Why does TH increase the synthesis of respiratory enzymes?
Because if one is burning more ATP, this will require that more enzymes are available to make it.
How does TH increase substrate availability?
glycogenolysis, glycolysis, gluconeogenesis
acts on gut to increase absorption of nutrients
TH increases cellular heat production when the rate of metabolism is increased. What is the mechanism?
TH increases uncoupling proteins in the ETC that take H+ and transport it back into the matrix instead of thru the ATPase. This produces heat.
What is TH’s effect on mitochondria?
it increases the number and or size
TH upregulates ___-___ receptors that are critical to responses to activation of the sympathetic nervous system. It also increases sensitivities to ___ in both the endocrine and nervous system.
Beta-adrenergic; catecholamine
TH regulates the production of ___ hormone, primarily in bone.
growth
Why is TH important for CNS development and function?
At neuronal growth cones, precursors for axon/dendrite are stimulate to grow by TH
It plays a role in the myelination of axons
In adults, it maintains alertness and speed of reflexes
What is the most common endocrine disease worldwide?
thyroid disease. Most conditions are due to hypothyroidism. Diabetes in the US
T/F. An enlarged thyroid forms a goiter, but only in cases of hyperthyroidism.
False, An enlarged thyroid often forms a goiter, and some forms of BOTH hypo- and hyperthyroidism can lead to development of a goiter.
Hypothyroidism is most often caused by a ___ defect of the thyroid gland. In 95% of cases, ___ deficiency (1 billion people worldwide) or ___ to the gland is involved.
primary; iodine; damage
What happens without iodine?
There is insufficient production of TH leading to lack of negative feedback, which increases TRH and TSH secretion. This causes a growth in goiter
How is iodine deficiency reversed?
by adding iodine to the diet. Iodized salt contains 1 NaI per 10,000 NaCl.
What is the consequence of iodine deficiency during prenatal development?
moderate deficiency (10-15 point reduction in IQ)
cretinism
miscarriage or stillbirth
Growth and neural development is impaired
What is another name for the primary hypothyroidism disease known as Hashimoto’s disease?
autoimmune thyroiditis
How can the thyroid gland be damaged or destroyed?
surgical or radiation for thyroid cancers
In the case of autoimmune thyroiditis, damaged or destroyed gland or dysfunction associated with illness (viral infection), the thyroid gland cannot make TH even if sufficient iodine is available. So, how is it treated?
the defects must be treated with exogenous TH.
Levothyroxine (synthyroid)
Secondary effects arise from deficits in ___ or ___ synthesis and release, or receptor deficits. How are these treated?
TRH; TSH
The thyroid function is fine, but the gland is not receiving the proper stimulatory input. Therefore, something that stimulates the action of TSH.
What are the symptoms of mild hypothyroidism?
sensitivity to cold and slight weight gain. These cases are often not diagnosed.
The symptoms of moderate hypothyroidism are due to the effects of reduced ___-___ receptors and the disruption of responses to ___ stimulation.
Beta-adrenergic; catecholaminergic
The symptoms include fatigue, reduced bloodflow, changes in skin tone, sluggish gastrointestinal motility and mental function.
What is the name of the condition that is associated with severe hypothyroidism?
myxedema
Severe ___ is due to accumulation of ___ in the extracellular/intersitital fluid; typically most obvious in the ___.
bloating; glycosaminoglycans; face
Hyperthyroidism or ___ results from having too ___ TH and is much ___ common than hypothyroidism.
thyrotoxicosis; much; less
What are two primary defects that can cause hyperthyroidism?
- thyroid tumors that produce TH without regulation by TSH
2. inflammation of the gland that leads to the production of excess TH.
___ disease is an autoimmune disease where ___ are produced against ___ and they can activate the ___ receptor. Therefore, there is no ___ regulation of thyroid function.
Graves; antibodies; TSH; TSH; feedback
In Graves disease, ___ concentrations are high even though ___ (and ___) are low due to the feedback effects of increased ___.
TH; TSH; TRH; TH
T/F. Graves disease is more common in women than in men.
True.
___ ___ is hyperthyroidism that results from consuming excess thyroid hormone either in medication (hypo patient) or inappropriately processed meat.
Thyrotoxicosis factitia
What do secondary defects that cause hyperthyroidism include?
tumors (in pituitary) that secrete TSH without responding to feedback control by TH.
What can develop in cases of Graves disease that are caused by hyperstimulation of the TSH receptor even though TSH levels are low?
Goiter
T/F. In hyperthyroidism, metabolic and nervous system responses include heat intolerance, weight loss, increased appetite, sweating, and hypersensitivity of catecholaminergic responses.
True.
A general increase in activity of the sympathetic nervous system seen in hyperthyroidism is known as ___ ___.
thyroid storm
What ocular symptoms are seen in hyperthyroidism patients?
exopthalmy, lid lag. and decreased visual acuity
What two treatment options for hyperthryoid patients must be followed by replacement of TH to avoid hypothyroidism?
- surgical removal of the gland
2. destruction using radioactive I (which can also affect other organs that concentrate iodine - salivary glands)
What is the function of antithyroid drugs?
they act to inhibit iodination of TYR
block the release of TH
ameliorate the effects of TH in peripheral tissues
Why is TH not considered as a weight loss drug?
risk for heart attack b/c of beta-adrenergic side effects
In hypothyroidism, ___ is associated with retarded tooth development and maxillary prognathism.
cretinism
Which thyroid disease has a exaggerated response to narcotics and barbiturates, myxedema of the lips and tongue, and diminished cardiac and respiratory function due to lack of beta-adrenergic receptors?
hypothyroidism
In hyperthyroidism, early eruption of teeth leads to ___.
malocclusion
Which thyroid condition results in hypersensitivity to catecholaminergic drugs, osteoporosis in jaw bones due to increased bone resorption, susceptibility to thyroid storm?
hyperthyroidism
