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ROSS Vet Prep > Endocrinology THYROID (Cell Bio) - new final > Flashcards

Endocrinology THYROID (Cell Bio) - new final Flashcards

1
Q

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

A

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

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2
Q

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 **
A

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 **
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3
Q

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
A

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
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4
Q

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.

A

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

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5
Q

THYROID GLAND - C cells

Parafollicular cells or ?-cells are located ? the follicles

 Secrete ?
 One of the hormones that regulate ? metabolism

A

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

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6
Q

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

A
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7
Q

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

A

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

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8
Q

SYNTHESIS OF THYROID HORMONES

  1. 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 ?)

  1. 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))
  2. ? tyrosines are linked together to form T3 and T4
  3. Thyroglobulin colloid is ? (into thyroid follicle cell) and combined with a ?
  4. lysosomal enzymes cleave T4 and T3 from thyroglobulin ? and hormones (T4, T3) diffuse from ? cell into the ?
A

SYNTHESIS OF THYROID HORMONES

  1. 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)

  1. 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))
  2. iodinated tyrosines are linked together to form T3 and T4
  3. Thyroglobulin colloid is endocytosed (into thyroid follicle cell) and combined with a lysosome
  4. lysosomal enzymes cleave T4 and T3 from thyroglobulin colloid and hormones (T4, T3) diffuse from follicle cell into the bloodstream (capillary)
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9
Q

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

A

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!)

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10
Q

THYROID HORMONE SYNTHESIS

In the thyroid follicle lumen, the ? ? (enzyme!) will facilitate the synthesis of ? hormones in 2 steps:

  1. 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)

A

THYROID HORMONE SYNTHESIS

In the thyroid follicle lumen, the THYROID PEROXIDASE (enzyme!) will facilitate the synthesis of thyroid hormones in 2 steps:

  1. 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)

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11
Q

THYROID HORMONE SYNTHESIS

  1. Organification
  2. 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)

A

THYROID HORMONE SYNTHESIS

  1. Organification
  2. 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)

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12
Q

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 ? **

A

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.

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13
Q

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

A

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

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14
Q

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)

A

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

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15
Q

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

A

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

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16
Q

HORMONE CLEARANCE

T4 and T3 Hormones are “ ? ” from the plasma in several ways

 ? (formation of sulfates and ? mainly in kidneys and liver respectively)

 Deionization (metabolic ? by the tissues, mainly in
-> ?
-> skeletal muscle
-> ?

** Excretion by the ? into the bile (than in the feces)
 Excretion by the ? into the urine **

** A decreased metabolic clearance rate can cause an excessively high concentration of ? hormones in the ?
 Ex: ? disease **

A

HORMONE CLEARANCE

T4 and T3 Hormones are “ cleared ” from the plasma in several ways

 CONJUGATION (formation of sulfates and glucuronides mainly in kidneys and liver respectively)

(2 ways: excrete and make T4 and 3 inactive)

 Deionization (metabolic breakdown by the tissues, mainly in
-> liver
-> skeletal muscle
-> kidneys

** Excretion by the liver into the bile (than in the feces)
 Excretion by the kidney into the urine **

** A decreased metabolic clearance rate can cause an excessively high concentration of thyroid hormones in the blood
 Ex: LIVER DISEASE **

17
Q

ACTIONS OF THYROID HORMONES

Thyroid hormones are the primary factors for the control of ? metabolism
o Bind to ? receptors and initiate the transcription of ? (? synthesis!)
o Are important for the normal ? activity of all tissues

Physiological actions are not ? determined:
o Most of the knowledge comes from the research with the ? (hypo or hyperthyroidism)

A

ACTIONS OF THYROID HORMONES

Thyroid hormones are the primary factors for the control of cellular metabolism
o Bind to nuclear receptors and initiate the transcription of mRNA (? synthesis!)
o Are important for the normal metabolic activity of all tissues

Physiological actions are not precisely determined:
o Most of the knowledge comes from the research with the disesaes (hypo or hyperthyroidism)

18
Q

ACTIONS OF THYROID HORMONES

  1. Increase the numbers and activity of ?
    o Increase the rate of formation of ? (produced by FFAs and glucose)
    • Could be due to ? activity of the cells
  2. Increase the ? ? rate of cells
    o ? = is the ? rate of energy expenditure per unit time at rest
    o Cellular enzymes increase the activity in response to ? hormones
     T3 or T4? regulates the activity and gene
    expression of Na+/K+ ATPase

o Calorigenic: ↑ ? consumption of tissues ↑ ? production
o Weight ? in hyper, weight ? in hypothyroidism

  1. ? Metabolism
    o Increase absorption of intestinal ?
    o Facilitate the movement of ? into fat and muscle tissues
  2. ? Metabolism
    o Increase ? (to produce ATP from fat) → enhance mobilization of ?, increasing ? available for β-oxidation
    o Thyroid stimulation decreases plasma ? and liver ?
     Increase cellular uptake and degradation of ?, increase ? secretion in the bile
    → Hypothyroid individuals can present ? and ? liver
  3. ? & development are influenced by thyroid hormones
    o TH permit maturation of the nervous system (CNS)
     If inadequate thyroid hormones: reduced ? abilities, ?
    o Work in conjunction with ? Hormone (GH)
  4. Increase ? flow and ? output
    o Possibly through interactions with ?
  5. Increase ? rate
    o Direct effect on the excitability of the heart
  6. ? effects
    o Increase ? and ? intake
    o Increase ? motility
    *Hyperthyroidism can cause diarrhea (hypermotility)
  7. Thyroid hormone-induced ? in amphibians and fish larvae
A

ACTIONS OF THYROID HORMONES

  1. Increase the numbers and activity of mitochondria
    o Increase the rate of formation of ATP (produced by FFAs and glucose)
    • Could be due to increased activity of the cells
  2. Increase the basal metabolic rate of cells
    o BMR = is the minimal rate of energy expenditure per unit time at rest
    o Cellular enzymes increase the activity in response to thyroid hormones
     T3 regulates the activity and gene
    expression of Na+/K+ ATPase

o Calorigenic: ↑ oxygen consumption of tissues ↑ heat production
o Weight loss in hyper, weight gain in hypothyroidism (the more the thyroid hormones the higher the metabolic rate thus higher the weight loss)

  1. Carbohydrate Metabolism
    o Increase absorption of intestinal glucose
    o Facilitate the movement of glucose into fat and muscle tissues
  2. Lipids Metabolism
    o Increase lipolysis (to produce ATP from fat) → enhance mobilization of fat, increasing FFAs available for β-oxidation
    o Thyroid stimulation decreases plasma cholestrol and liver fat
     Increase cellular uptake and degradation of LDL, increase cholestrol secretion in the bile
    → Hypothyroid individuals can present hyperlipidemia and fatty liver
  3. Growth & development are influenced by thyroid hormones
    o TH permit maturation of the nervous system (CNS)
     If inadequate thyroid hormones: reduced metabolic abilities, lethargic
    o Work in conjunction with Growth Hormone (GH)
  4. Increase blood flow and cardiac output
    o Possibly through interactions with catecholamines
  5. Increase heart rate
    o Direct effect on the excitability of the heart
  6. GI effects
    o Increase appetite and food intake
    o Increase GI motility
    *Hyperthyroidism can cause diarrhea (hypermotility)
  7. Thyroid hormone-induced metamorphosis in amphibians and fish larvae
19
Q

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)

A
20
Q

ENDOCRINE SYSTEM
PATHOLOGIES ASSOCIATED WITH THE THYROID HYPERTHYROIDISM

FYI Most common endocrinopathy of cats
 Main cause is ? or tumors of the ? gland (thyroid adenoma)
 typically affects ?-aged to older cats
 is characterized by ? growth of thyroid (epithelial) follicles (abnormality in the signal transduction of the thyroid cell) FYI

focus on symptoms here!
Symptoms related to hypermetabolism
 ? loss
 increased ? (polyphagia)
 increased ? and ? (polydipsia and polyuria)
 ?, diarrhea
 ? and unkempt appearance
 ?, ?cardia

A

THYROID HYPERTHYROIDISM

Most common endocrinopathy of cats
 Main cause is hyperplasia or tumors of the thyroid gland (thyroid adenoma)
 typically affects middle-aged to older cats
 is characterized by autonomous growth of thyroid (epithelial) follicles (abnormality in the signal transduction of the thyroid cell)

Symptoms related to hypermetabolism
 weight loss
 increased appetite (polyphagia)
 increased thirst and urination (polydipsia and polyuria)
 vomiting, diarrhea
 shedding and unkempt appearance
 hyperactivity, tachycardia

21
Q

ENDOCRINE SYSTEM PATHOLOGIES ASSOCIATED WITH THE THYROID HYPOTHYROIDISM

More common in dogs

Primary causes (strong breed disposition):
 lymphocytic ? (inflammation)
 ? thyroid dysgenesis (inherited defects in the hypothalamic-pituitary-thyroid axis)
 ? transport defects
 ?, iodine deficiency
 ? thyroiditis

Secondary causes:
 ? tumors
 ? therapy
 ?

Symptoms related to hypometabolism:
 lethargy and ? (most common)
 ? hair and truncal or tail ? (no hair), retention of ? hair
 ? disorders (interferes in cycling)
 ?

A

ENDOCRINE SYSTEM PATHOLOGIES ASSOCIATED WITH THE THYROID HYPOTHYROIDISM

More common in dogs

Primary causes (strong breed disposition):
 lymphocytic thyroiditis (inflammation)
 congenital thyroid dysgenesis (inherited defects in the hypothalamic-pituitary-thyroid axis)
 T4 transport defects
 Goitrogens, iodine deficiency
 autoimmune thyroiditis

Secondary causes:
 Pituitary tumors
 radiation therapy
 glucocorticoids

Symptoms related to hypometabolism: (LDRC)
 lethargy and obesity (most common)
 dull hair and truncal or tail alopecia (no hair), retention of puppy hair
 reproductive disorders (interferes in cycling)
 constipation

22
Q

PATHOLOGIES ASSOCIATED WITH THE THYROID IODINE DEFICIENCY IN CATTLE, SHEEP, GOATS - Goiter

Iodine deficiency may be due to:
 Inadequate * ? intake * of ? (i.e.,
iodine deficient soils) or
 Consumption of ? containing
compounds that either interfere with iodine uptake by the thyroid gland or with normal ? of thyroid hormones (* ? *)
* Goitrogens – brassicas, white clover pastures

** Iodine deficiency typically results in enlargement of the ? glands (goiter). **

Large firm, non-fluctuant, swelling of the ? neck in an otherwise healthy animal is likely to be goiter.

A

Iodine deficiency may be due to:
 Inadequate * DIETARY intake * of IODINE (i.e.,
iodine deficient soils) or
 Consumption of feed containing
compounds that either interfere with iodine uptake by the thyroid gland or with normal synthesis of thyroid hormones (* ? *)
* Goitrogens – brassicas, white clover pastures

** Iodine deficiency typically results in enlargement of the thyroid glands (goiter). **

Large firm, non-fluctuant, swelling of the ventral neck in an otherwise healthy animal is likely to be goiter.

ROSS Vet Prep (72 decks)

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