Lecture 5 Flashcards
What is the thyroid gland?
Location, cell types, features
Located on anterior surface of the trachea, composed of left and right lobes, and a small connecting branch or isthmus
Size of gland is variable (depends on environment, etc)
Easily palpable (can be felt with fingers when something is wrong)
Thyroid hormone are the only ones that require iodine as essential trace element
Thyroid hormone are peptides that’s have receptors in the nucleus and not on cell membrane
2 cell types of thyroid gland:
- Follicular cells- secrete thyroxine, T4, T3
- Parafollicular cells or C cells that release calcitonin
Slides 9-10
How are thyroid hormones synthesized?
Thyroid hormones are synthesized by the follicular epithelial cells of the thyroid gland
Follicular lumen is filled with glycoprotein mixture known as colloid
Production of thyroid hormone requires adequate amounts of iodine (supplied in diet)
Synthesis of thyroid hormones is partly intracellular and partly extracellular
Slide 11
What are the 8 steps of thyroid hormone synthesizing?
Thyroid hormones are made by ionizing tyrosine residues om thyroglobulin and are stored as part of thyroglobulin molecules in thyroid follicles
- Synthesis of thyroglobulin (TG)
- Iodine trapping
- Oxidation of iodide
- Iodination of thyrosine
- Coupling reaction
- Endocytosis of thyroglobulin
- Hydrolysis of T3 and T4 from thyroglobulin
- Deiodination
Slides 12-21
What is step 1: synthesis of thyroglobulin (TG)?
Occurs in thyroid follicular cell
Glycoprotein rich in tyrosine is synthesized in the rough endoplasmic reticulum, modified in the Golgi body and packaged into secretory vesicles for exocytotic release into the lumen
Slide 13
What is step 2: iodine trapping?
Na/I symporter or cotransporter located at basolateral membrane fueled by the energy of the Na electrochemical gradient
Thyroid stimulating hormone (TSH) enhances Na/I symporter activity, and this iodine trapping
Elevated iodine levels inhibit the pump
Slide 14-15
What is step 3: oxidation of iodide?
Iodide exiting the follicular epithelium is oxidized you I2 in the follicular lumen by the enzyme thyroid peroxidase
Negatively charged iodide cannot bind tyrosine of the thyroglobulin until they undergo oxidation
Slide 16
What is step 4: iodination of thyrosine?
Thyroid peroxidase catalyzes the formation of mono- and di- iodothyrosine in a reaction involving iodine and the thyrosine moieties of thyroglobulin
The iodinated thyroglobulin is stored inside the follicular lumen as colloid until the thyroid gland is stimulated by TSH
slide 17
What is step 5: coupling reaction?
Thyroid peroxidase used conjugation to catalyze the formation of tetraiodothyronine (T4) from 2 molecules of di-iodothyrosine
Thyroid peroxidase also catalyze formation of T3 from one molecule of di-iodothyrosine and mono-iodothyrosine
10 times more T4 produced than T3
Slide 18
What is stage 6: endocytosis of thyroglobulin?
This process occurs after the stimulation of the thyroid gland by TSH
Iodinated thyroglobulin, T4 and T3 are endocytosed into the follicular epithelial cells from thyroid colloid
Endocytic vesicle woth colloid droplets moves towards the basolateral membrane
Slide 19
What is stage 7: proteolysis and hydrolysis of T3 and T4 from thyroglobulin?
Lysosomal proteases within the endocytic vesicle hydrolyze the peptide bonds to release T3 and T4 from the thyroglobulin
Slide 20
What is step 8: deiodination?
Any uncoupled monoiodotyrosine or diiodotyrosine at stage 5 are attached to thyroglobulin and deiodinated inside the follicular cells by the enzyme thyroid deiodinase
Slide 21
What are the 3 functions of the thyroid gland?
- Collect and transport iodine
- Synthesis of thyroglobulin and secreting it into the colloid
- Remove the thyroid hormones from thyroglobulin and secrete them into the systemic circulation
What are the physiological effects of the thyroid hormone on the body?
(5 of them)
Thyroid hormone indispensible for healthy growth and development, iodine deficiency can lead to hypothyroidism and goiter
Thyroid hormones may increase basal metabolic rate by stimulating ineffective cycles of catabolism and anabolism
In muscle liver kidney thyroid hormone induced increases in O2 consumption are parallel to increases in activity of NaK pump
Stimulates thermogenesis
Stimulates carbohydrate, protein, and lipid metabolism
Slide 24
What are the effects of the thyroid hormones on these glands: Bone Liver Brain Heart Adipose tissue Muscle Gut
Bone- increase osteoblastic and osteoclastic activity, promote normal growth and skeletal development
Liver- triglyceride and cholesterol metabolism
Brain- axon growth and development
Heart- inotropic and chronotropic effect, reduces smooth muscle resistance of vessels
Adipose tissue- increases lipolysis
Muscle- increase protein breakdown
Gut- increase rate of carbohydrate absorption
What are the 2 active forms of thyroid hormones?
Two active forms: triiodiothyronine (T3) and tetraiodiothyronine (T4)
T3 exerts negative feedback on the anterior pituitary and hypothalamus, and is more physiologically active than T4 (since it has more affinity for tyrosine receptors
T4 has longer half life
Slide 26-27
What is the structure of T4, T3, and rT3?
T4, T3, and rT3 are products of coupling of 2 iodinated tyrosine derivatives
Reverse T3 (rT3) forms as an iodine is removed from the inner benzyl ring of T4 rT3 is present in equal amounts as T3
Slide 27
What are the 2 types of deiodinases?
5’/3’ deiodinase removes an iodine from the outer benzene ring of T4 producing T3
5/3 deiodinase removes an iodine from the inner benzene ring of T4 producing rT3
Slide 28
What are the 2 types of 5’/3’ deiodinase?
Type 1- present in high concentrations in the liver, kidneys, and thyroid
Generated most of the T3 that reach the general circulation
Type 2- found predominantly in the pituitary m, CNS, and placenta
Supply these tissues with local T3
Type 2 in the pituitary is producing T3 that is responsible for feedback inhibition of thyroid stimulating hormone (TSH)
How do thyroid hormones act on target cells?
Free extracellular T4 and T3 enter target cell, once T4 inside cell cytoplasmic 5’/3’ deiodinase conveys much of T4 to T3 so the levels of T4 and T3 are equal
Binding of T4 or T3 to thyroid receptor regulates transcription of thyroid response elements in genes
Slide 30-31
How are thyroid hormones transported?
Thyroid hormones (T4 and T3) circulate freely or bound to plasma proteins (thyroxine-binding globulin)
T4 is bound more tightly to plasma proteins than T3
Only 0.02% of T4 is free
0.5% of T3 is free
Slide 32
How are thyroid hormones regulated?
Hypothalamic-pituitary-thyroid axis
Pituitary regulates synthesis and secretion of thyroid hormones through release of thyrotropin (TSH) from anterior pituitary
Hypothalamus stims release of TSH through thyrotropin-releasing hormone (TRH)
TRH from hypothalamus stims thyrotrophs of the anterior pituitary to secrete thyrotropin, which stims T3/4 synthesis
Slide 33-35
What are primary and secondary hypothyroid disorders?
Primary- problems with thyroid gland (gland destroyed by immune cells; radioactive iodine; surgery; tumor; iodine deficiency)
Secondary- problems with pituitary or hypothalamus
Hypothyroidism caused by hyposecretion of the hormone
Disorders associated with hypothyroidism: cretinism (severe retardation), myxedema (dermal edema), iodine-deficient goiter
Slide 36-37
