Endocrinology THYROID (Cell Bio) - new final Flashcards
THYROID GLANDS - Anatomy
In most mammals, the thyroid glands are located ? (at the back of) to the trachea at the level of the ? or ? tracheal ring
THYROID GLANDS - Anatomy
In most mammals, the thyroid glands are located caudal (at the back of) to the trachea at the level of the first or second tracheal ring
CHEMICAL STRUCTURE OF THYROID HORMONES
Amines (recall)
- derived from the amino acid “? “
-> catecholamines (hydrophobic or
hydrophilic?)
-> T3 and T4 thyroid hormones
= hydrophobic or hydrophillic?
- Blood transport
-> Catecholamines circulate unbound in the blood as they are hydrophilic
-> Thyroid hormones need
** ?-binding ? (TBG) and ? which are
produced by the liver **- Half-life depends on the hormone
-> Thyroxine = 7-10 ?
-> Epinephrine = 1 ? - catecholamines bind to the * cell
membrane ?* as they are hydrophilic so can’t cross the PM made of hydrophobic tails - ** Thyroid hormones bind to ? receptors **
- Half-life depends on the hormone
CHEMICAL STRUCTURE OF THYROID HORMONES
Amines (recall)
- derived from the amino acid “TYROSINE “
-> catecholamines (hydrophilic)
-> T3 and T4 thyroid hormones
= hydrophobic like regular amines
(since hydrophobic they will bind to a carrier protein to be transported in cell)
- Blood transport
-> Catecholamines circulate unbound in the blood as they are hydrophilic
-> Thyroid hormones need
** Thyroxine-binding globulin (TBG) and albumin which are produced by the liver **- Half-life depends on the hormone
-> Thyroxine = 7-10 days
-> Epinephrine = 1 minute - catecholamines bind to the * cell
membrane receptors* as they are hydrophilic so they can’t cross the PM made of hydrophobic tails - ** Thyroid hormones bind to NUCLEAR receptors **
- Half-life depends on the hormone
THYROID GLAND
Thyroid tissue consists of numerous ?-like structures called thyroid ? that vary in ?
- Follicular cells are arranged in a ? pattern
follicular cells are a single layer of ?
follicular cells ? the thyroid hormones
THYROID GLAND
Thyroid tissue consists of numerous sac-like structures called thyroid follicle that vary in size
- Follicular cells are arranged in a circular pattern
follicular cells are a single layer of epithelium
follicular cells make/synthesize the thyroid hormones
THYROID GLAND - Colloid
The follicles are filled with * COLLOID *
Colloid: viscous ?-rich liquid
(rich in ? = glycoprotein)
colloid -> The main * ? * of the thyroid hormones (active)
* Within the lumen created by ? cells
* This form of storage allows mammals to withstand periods of ? deprivation without an immediate effect on the production of ? hormones.
THYROID GLAND - Colloid
The follicles are filled with * *
Colloid: viscous protein-rich liquid
(rich in thyroglobulin = glycoprotein)
colloid -> The main * STORAGE * of the thyroid hormones (active)
* Within the lumen created by glandular cells
* This form of storage allows mammals to withstand periods of IODINE deprivation without an immediate effect on the production of thyroid hormones.
NOTE: colloid STORES thyroid hormones but doesn’t MAKE thyroid hormones
THYROID GLAND - C cells
Parafollicular cells or ?-cells are located ? the follicles
Secrete ?
One of the hormones that regulate ? metabolism
THYROID GLAND - C cells
Parafollicular (para means around so located outside the follicles) cells or C-cells are located outside the follicles
Secrete calcitonin
One of the hormones that regulate calcium metabolism
THYROID HORMONE SYNTHESIS
So hypothalamus will be sensing the levels of T3 and T4 in the blood. Okay. So if I have reduced levels of T3 and T4, the hypothalamus will sense it and release TRH (thyrotropin-releasing hormone)
TRH goes to adenohypophysis through the hypothalamic-hypophyseal portal system.
When TRH reaches anterior pituitary gland/adenohypophysis, then the thyrotropes are stimulated which are the group of cells inside the adenohypophysis to produce TSH
Then TSH goes to blood circulation (blue in adenohypophysis in pic) and reaches thyroid gland that is found around trachea so the thyroid gland produces and secretes T3 and 4 in blood (target tissue) - majority of hormone is T4, just a lil bit T3
THYROID HORMONE SYNTHESIS
2 molecules of importance:
- ?
- ? (I2)
TYROSINE is part of a large protein called
? (glycoprotein)
THYROGLOBULIN (TG)
-> is synthesized within the
? epithelial cell (thyroid hormones also made from this) and secreted into the ?
-> Contains a large number of ? amino acid residues
-> ? is the major substrate that combines with iodine to form thyroid hormones
THYROID HORMONE SYNTHESIS
2 molecules of importance:
- TYROSINE
- IODINE (I2)
TYROSINE is part of a large protein called
thyroglobulin (glycoprotein)
THYROGLOBULIN (TG)
-> is synthesized within the follicle epithelial cell (thyroid hormones are also made from this) and secreted into the colloid
-> Contains a large number of tyrosine amino acid residues (so tyrosine is a subunit of thyroglobulin)
-> Tyrosine is the major substrate that combines with iodine to form thyroid hormones
SYNTHESIS OF THYROID HORMONES
- In the thyroid follicle cell, ? is made and discharged into the follicle ?
2a. trapping (active uptake of ? I-)
(Iodide from the capillary moves into thyroid follicle cell as seen in pic)
2b. oxidation occurs: ? (iodide (I-) into ?)
- iodine enters the follicle ? where it is attached to ? in colloid, forming DIT (T2) and MIT (T1)
(thyroglobulin colloid has iodine attached to tyrosine (blue ones are iodine)) - ? tyrosines are linked together to form T3 and T4
- Thyroglobulin colloid is ? (into thyroid follicle cell) and combined with a ?
- lysosomal enzymes cleave T4 and T3 from thyroglobulin ? and hormones (T4, T3) diffuse from ? cell into the ?
SYNTHESIS OF THYROID HORMONES
- In the thyroid follicle cell, thyroglobulin is made and discharged into the follicle lumen
2a. trapping (active uptake of ioDIDE I-)
(Iodide from the capillary moves into thyroid follicle cell as seen in pic)
2b. Oxidation occurs: an active form of iodine (iodide (I-) into iodine)
- iodine enters the follicle lumen (colloid is in follicle lumen) where it is attached to tyrosine (yellow things) in colloid, forming DIT (T2) and MIT (T1)
(thyroglobulin colloid has iodine attached to tyrosine (blue ones are iodine)) - iodinated tyrosines are linked together to form T3 and T4
- Thyroglobulin colloid is endocytosed (into thyroid follicle cell) and combined with a lysosome
- lysosomal enzymes cleave T4 and T3 from thyroglobulin colloid and hormones (T4, T3) diffuse from follicle cell into the bloodstream (capillary)
THYROID HORMONE SYNTHESIS
Iodine (I2) comes from the ?
It gets converted to ? (I-) in the ** ? ** and it is transported to the ? follicle cells
Thyroid follicle cells trap the iodide (I-) via an ? ? process (Na+/I- cotransporter)
* ? provides the driving force to bring iodide I- into the cell
* Intracellular [iodide] is 25 – 200 x higher than ? of the cell
THYROID HORMONE SYNTHESIS
Iodine (I2) comes from the diet
It gets converted to iodide (I-) in the ** intestinal tract ** and it is transported to the ** thyroid follicle cells **
Thyroid follicle cells trap the iodide (I-) via an “active transport process” (Na+/I- cotransporter)
* sodium provides the driving force to bring iodide I- into the cell
* Intracellular [iodide] is 25 – 200 x higher than outside of the cell
(symport and it is a secondary active transport (as it is driven by sodium -> sodium-potassium ATPase pump)
what kind of transport primary secondary - exam question!)
THYROID HORMONE SYNTHESIS
In the thyroid follicle lumen, the ? ? (enzyme!) will facilitate the synthesis of ? hormones in 2 steps:
- Organification: Oxidation of ? back to ? (I−→I2) + ? iodination
Tyrosine ? (Iodine combine to the tyrosine amino acid on ? protein)
Tyrosyl ring can accommodate 2 ? molecules
-> If 1 molecule attaches = ?TYROSINE (MIT)
-> If 2 molecules attach = ?TYROSINE (DIT)
THYROID HORMONE SYNTHESIS
In the thyroid follicle lumen, the THYROID PEROXIDASE (enzyme!) will facilitate the synthesis of thyroid hormones in 2 steps:
- Organification: Oxidation of iodiDe back to iodine (I−→I2) + tyrosine iodination
Tyrosine iodination (Iodine combine to the tyrosine amino acid on thyroglobulin protein)
Tyrosyl ring can accommodate 2 iodine molecules
-> If 1 molecule attaches = MONOIODOTYROSINE (MIT)
-> If 2 molecules attach = DIIODOTYROSINE (DIT)
THYROID HORMONE SYNTHESIS
- Organification
- Coupling (fusion) of two of these ? tyrosines
1 DIT + 1 DIT = T4 or ? or ? or Thyroxine
-> 4 ? molecules
1 MIT + 1 DIT = ? or Triiodothyronine
-> 3 ? molecules
THYROID HORMONE storage and secretion
T3 and T4 remain attached to ? molecule and stored in the ? until secretion
o Unique type of storage (allows the thyroid to store a ? reserve of the hormone)
T4 is the major hormone produced by the ? cells
o Only ? amounts of T3 are produced by the ? gland
o Major source of T3 is ? ? of T4 in target tissues (enzyme dependent - deiodinases)
THYROID HORMONE SYNTHESIS
- Organification
- Coupling (fusion) of two of these iodinated tyrosines
1 DIT + 1 DIT = T4 or tetraiodothyronine or thyronine or Thyroxine
-> 4 iodine molecules
1 MIT + 1 DIT = T3 or Triiodothyronine
-> 3 ? molecules
THYROID HORMONE storage and secretion
T3 and T4 remain attached to thyroglobulin molecule and stored in the colloid until secretion
o Unique type of storage (allows the thyroid to store a large reserve of the hormone)
T4 is the major hormone produced by the follicular cells
o Only small amounts of T3 are produced by the thyroid gland
o Major source of T3 is peripheral deiodination of T4 in target tissues (enzyme-dependent - deiodinases)
THYROID HORMONE SECRETION
Secretion process:
* Endocytosis of iodinated thyroglobulin from the follicle ? into the ? ? cell
* Lysosomes fuse to ? vesicle → enzymes cleave ? and ?
* ** ? and ? are released and freely pass through the ? ? cell membrane (lipophilic) into the ? **
THYROID HORMONE SECRETION
Secretion process:
* Endocytosis of iodinated thyroglobulin from the follicle lumen into the follicle epithelial cell
* Lysosomes fuse to thyroglobulin vesicle → enzymes cleave T3 and T4
* *** T3 and T4 are released and freely pass through the follicle thyroid cell membrane (lipophilic) into the bloodstream **:
summary: first and foremost thyroglobulin is made in follicle epithelial cell and discharged into the follicle lumen (tyrosines go into follicle lumen) after which iodide goes into follicle epithelial cell from the capillary/bloodstream and then goes into the follicle lumen where it gets oxidized into iodine and
then iodine gets attached to tyrosine in the lumen and the iodinated tyrosines link together to form T3 and T4. then the thyroglobulin colloid which comprises the iodinated tyrosines, gets endocytosed into follicle epithelial cell and then gets combined with lysosome, lysosomal enzymes cleave T3 and 4 from thyroglobulin and the hormones, T3 and T4 then diffuse into capillaries/bloodstream.
THYROID HORMONE TRANSPORT
Thyroid hormones are transported in ? attached to ?
- ?-binding ?
- ?
(both synthesized in which organ?)
** A ? amount of hormone is free in the circulation **
* ** Free T4 and T3 are available to diffuse into the ? cells **
* Once free T4 or 3? has entered the target cell, most of it will be converted to ?
-> By ? ? in the cytosol
THYROID HORMONE TRANSPORT
Thyroid hormones are transported in plasma attached to proteins
- thyroxine-binding globulin (TBG)
- ALBUMIN
(both synthesized in which organ?- liver)
** A small amount of hormone is free in the circulation **
* ** Free T4 and T3 are available to diffuse into the target cells **
* Once free T4 has entered the target cell, most of it will be converted to T3
-> By iodothyronine deiodinases in the cytosol
THYROID HORMONE TRANSPORT
The equilibrium between free and bound hormone in the blood plasma is easily shifted because of ? or ? situations
* Such as the increase in ? concentrations that occurs during ?
Adjustments to maintain a normal amount of ? hormone occur rapidly with:
A decline in the rate of ? or
Stimulation of ? hormone ?
through the release of thyroid-stimulating hormone (TSH)
THYROID HORMONE TRANSPORT
The equilibrium between free and bound hormone in the blood plasma is easily shifted because of physiological or pharmocological situations
* Such as the increase in estrogen concentrations that occurs during pregnancy
Adjustments to maintain a normal amount of free hormone occur rapidly with:
A decline in the rate of metabolism or
Stimulation of thyroid hormone production
through the release of thyroid-stimulating hormone (TSH)
picture: total T3 AND T4: amount of t3 and 4s bound to carrier proteins + the free hormones (T4 not bound to carrier protein)
T4 — deiodination —> T3
HORMONE CLEARANCE
The rate of the removal of the hormone from the ? can be measured
- It is called the ? ? RATE (MCR)
- The metabolic clearance rate interferes with ? concentrations
MCR = RATE OF THE DISAPPEARANCE OF HORMONE FROM PLASMA divided by CONCENTRATION OF HORMONE
HORMONE CLEARANCE
The rate of the removal of the hormone from the blood can be measured
- It is called the METABOLIC CLEARANCE RATE (MCR)
- The metabolic clearance rate interferes with hormone concentrations
MCR = RATE OF THE DISAPPEARANCE OF HORMONE FROM PLASMA divided by CONCENTRATION OF HORMONE
REGULATION OF THYROID HORMONES THROUGH NEGATIVE FEEDBACK LOOP
the thyroid hormones T3 and T4 send negative feedback from the thyroid to the anterior pituitary and then it sends a negative feedback to the hypothalamus to stop releasing TRH
Stress also sends negative feedback to the hypothalamus to stop producing TRH thus blocking the release of TSH from (thyrotopes from) anterior pituitary to thyroid (target organ)
CONSTANT STRESS -> THYROID PROBLEMS (as not enough TRH being produced)
