Lecture 14: Thyroid Gland Flashcards
1
Q
Where is the thyroid gland located
A
below Larynx alongside trachea
2
Q
What is the follicule
A
The functional units of the thyroid gland, composed of spheres filled with colloid surrounded by a single layer of folluicular cells
3
Q
What is thyroglobulin
A
Glycoprotein rich in tyrosine, is the main component of colloid
Harbors thyroid hormones at various stage of synthesis
4
Q
What are the two endocrine cells of the thyroid gland
A
Follicular and C cells
5
Q
What are follicular cells
A
Major secretory cells at various stages of thyroid hormone synthesis. They surround the follicles
6
Q
What are C-cells
A
Cells that secrete calcitonin and are important for Ca2+ balance
7
Q
What type of hormone is thyroid hormone
A
Amine, made from two tyrosine molecules with three or four iodine molecules
8
Q
Iodine is converted to ___ and transported to thyroid gland
A
Iodide
9
Q
Are thyroid molecules hydrophobic or hydrophilic
A
Hydrophobic
10
Q
Why is storage of this hormone important
A
Iodine is of dietary origin so may vary and it is needed to form the thyroid hormone
11
Q
How much thyroid hormone does the thyroid gland store
A
Enough for 3-4 months
12
Q
What is the HPT axis
A
Regulates thyroid gland function, thyroid gland growth and T3/T4 synthesis
13
Q
Where is thyrotropin releasing hormone released from and what does it stimulate
A
Released from hypothalamus and stimulates release of thyroid stimulating hormone from pituitary thyrotropes
14
Q
TSH stimulates the release of
A
T3 and T4
15
Q
How is the HPT axis regulated
A
Negative feedback of the thyroid hormone at the hypothalamus and anterior pituitary
16
Q
HPT axis is regulated by ___ rhythm
A
Diurnal
17
Q
The HPT axis requires dietary intake of what
A
Iodine
18
Q
Describe how release of TRH can be used to measure ACTH in horses who potentially have Cushing’s
A
Pituitary adenoma cells lose receptor specificity for hypothalamic releasing and usually TRH will stimulate release of the corticotrophs in the pars intermedia to release ACTH
Measure at t=0, 0, 30 minutes
19
Q
T3 or T4: rapid action and degradation, 10x more binding affinity, metabolically active, signaling form
A
T3
20
Q
T3 or T4: slow to respond, slow to bind receptors, less active, is the blood transport form
A
T4
21
Q
What is the precursor for thyroid hormone synthesis
A
Tyrosine
22
Q
During thyroid hormone synthesis, iodides are attached to two tyrosine to create what two different molecules
A
Monoiodothyrosine (MIT) and diiodothyrosine (DIT)
23
Q
During thyroid hormone synthesis: what coupling reactions take place to make T3 and T4
A
- MIT + DIT—> T3
- DIT + DIT—> t4
24
Q
What is the first step in thyroid hormone synthesis
A
Thyroglobulin is synthesized in follicle cells and exocytosed to colloid
25
The second step of thyroid synthesis involves ___ being transported by secondary active transport Na+/K+ ATPase
Iodide
26
what is iodide trapping
All iodide in body is concentrated in thyroid
27
Step 3 of thyroid hormone synthesis involves the oxidation of iodide to active iodide by what enzyme
Thyroperoxidase (TPO)
28
In thyroid hormone synthesis the activated iodide exit through channels into the ___
Colloid
29
After activated iodide molecules exit into colloid, tyrosine iodination in the colloid occurs. What does that involve
Iodides in the colloid are quickly attached by thyroperoxidase to tyrosine molecules within the Tg molecule
30
What is the perioxidase coupling reaction during thyroid hormone synthesis that results in T3 and T4
Syntheses of thyroid hormone from MIT and DIT, peroxidase coupling of MIT and DIT with Tg molecule
31
DIT + DIT forms what form of thyroid hormone
T4 (thyroxine)
32
MIT + DIT forms what form of thyroid hormone
T3 (tri-iodothyronine)
33
After Tg-thyroid hormone complex is created where is it taken
Into follicular cell by phagocytosis
34
What must occur after Tg-thyroid is phagocytosed into follicular cell in order to make active T3 and T4
Lysosomes cleave Tg-complex
35
After cleavage of Tg-complex by lysosomes what happens to the lipophilic thyroid hormones
Diffuse through plasma membrane into circulation
36
What happens to leftover MIT’s and DIT’s after thyroid hormone synthesis
They are of no use
Storage form
37
What happens to iodide after thyroid hormone synthesis is complete
Unused iodide is cleaved from MIT and DIT by follicular deiodinase and returns to colloid
38
What does thyroid binding globulin bind
75% of T3/T4
39
What species have almost no thyroid binding globulin
Rabbits and guinea pigs
40
What does transthyretin bind
10% T4
41
Where does transthyretin transport T4 to
Secreted into cerebral spinal fluid and allows transport to nervous system
42
What does albumin bind
15% t4 and 25% t3
43
What percent of T4/T3 is free
1%
44
What organ only excretes free T3/T4
Kidney
45
What is the half life of T3
1 day
46
What is the half life of T4
7 days
47
What hormone fraction is important for thyroid hormone signaling and HPT feedback
Circulating free hormones
48
What hormone fraction of thyroid hormone allows for a serum reserve capacity
Bound hormones
49
Deiodinase cleaves iodine groups to make active T3 and T4, at what carbon is active T3 cleave
Carbon 5 of the outer ring
50
What organs does active T 3 go to
Liver and kidney
51
Deiodinase cleaves iodine groups to make active t3 and T4, at which carbon is the iodide removed to create reverse T3
Carbon 4 of inner ring
52
Where is type I deiodinase found
Liver, kidney, thyroid
53
Where is type II deiodinase found
Brain, pituitary, brown fat, thyroid, placenta, striated muscle
54
Where is type III deiodinase found
Brain, placenta, skin
55
Which deiodinase promotes thyroid signaling and which one inhibits
Deiodinase II promotes
Deiodinase III inhibits
56
What is the main effect of T3/T4
Regulate metabolic rate
57
How does direct regulation of thyroid hormone occur
Thyroid hormone binds to AdNT in inner mitochondrial member and, AdNT exchanges free ATP with ADP across inner mitochondrial membrane where it binds T3R receptor on mtDNA
58
How does the indirect regulation of T3 work
T3 binds T3R in nuclear genome, nuclear genes like NRF and PGC-1 influence mitochondrial biosynthesis include RNA polymerase mitochondria and mitochondrial transcription factor A
RNA polymerase and Mitochondrial transcription factor A will for to mtDNA along with thyroid hormone bound to T3R
59
What do thyroid hormone receptors bind on DNA
Thyroid response element
60
Unbound thyroid hormone receptor interacting with TRE leads to ___
Repression of the transcription through a co-repressor protein
61
The bound thyroid hormone receptor complex interacting with TRE leads to ____
Activation of transcription through coactivator proteins
62
How does T3 bound receptors affect Na+K+ ATPase
Stimulate/increase Na+/K + ATPase which increases O2 consumption, increased basal metabolic rate
63
How does T3 bound receptors impact uncoupling proteins
Increase uncoupling protein—> enhanced fatty acid metabolism and heat production without ATP synthesis
64
How does T3 bound receptor impact protein synthesis and degradation
Enhancing growth and differentiation with a net increase in catabolism
65
How does T3 bound receptors impact the liver
Liver opposes insulin by stimulating glucogenesis and glycogenolysis, acts synergistically with peripheral tissues to with insulin to facilitate glucose uptake
66
How does t3 bound receptors impact catecholamine receptors
Increase catecholamine receptors, enhancing effects of SNS
67
How does T3 bound receptors impact cholesterol
Increases cholesterol synthesis and LDLR regulation
68
What is the physiological effect of thyroid hormone on liver
Regulates triglyceride and cholesterol metabolism , lipoprotein metabolism
69
What is the physiological effect of thyroid hormone on bone
Increases bone maturation, promotes epiphyseal plate closure
70
What is the physiological effect of thyroid hormone on adipose tissue
Induces adipose tissue differentiation, lipid mobilization and storage, and thermogenesis
71
What is the physiological effect of thyroid hormone on cardiovascular system
Increases CO, increases blood following, decreases resistance
72
What is the physiological effect of thyroid hormones on pituitary
Regulates synthesis of pituitary hormones, stimulates GH and inhibits TSH
73
What is the physiological effect of thyroid hormone on the brain
Necessary for nerve atonal cell growth and devleopmen; controls expression of genes with associated myelnation and cell differentiation, migration
74
Hyper or hypothyroidism: increased HR, increased Cardiac contractility, increased cardiac output
Hyperthyroidism
75
Hyper or hypothyroidism: decreased heart rate, decreased cardiac contractillity, decreased CO
Hypothyroidism
76
Hyper or hypothyroidism: Increased vascular resistance, decreased RBF, decreased B-adrenergic receptor sin kindey
Hypothyroidism
77
Hyper or hypothyroidism: decreased RAAS, decrease filtration pressure, decrease GFR
Hypothyroidism
78
Hyper or hypothyroidism: increased RAAS, increased filtration pressure, increases GFR
Hyperthyroidism
79
Hyper or hypothyroidism: increased TGF, increased tubular mass, increased Na/k+ ATPase and decreased ability to concentrate urine
Hyperthyroidism
80
Hyper or hypothyroidism: decreased TGF, decreased tubular mass, decreased Na/K ATPase, decrease NHE activity, decreased urinary concentrating ability
Hypothyroidism
81
Clinical case: weight loss in feline- owner complained pet showed weight loss over 6 months, matted fur, Temp=103, owner reports healthy appetite and high activity: what is initial diagnosis and what could lead to increase temperature
Diagnosis: hyperthyroidism
Temp increase: increased basal metabolism
82
Clinical Case: weight loss feline cont. blood work shows T4=52nmol/L (normal: 1.3-32.3). MRI of head is unremarkable. What is most likely origin of hyperthyroidism
Primary hyperthyroidism- overactive thyroid gland
83
In HPT axis how does primary hyperthyroidism affect release of upstream hormones
Since thyroid gland is overactive and not due to overstimulation from hypothalamus or anterior pituitary, the hyperthyroidism will cause increased negative feedback on anterior pituitary, decreasing release of TSH
84
Clinical case: goiterism and failure to thrive: farmer complains of failure to thrive, prolonged gestation, kids born hairless and stunted growth. Also observe mass on neck. Pasture has abundant rapeseed, white clower and sparse grass. What is initial diagnosis and what is cause
Diagnosis: hypothyroidism
Cause: thioglycosides in rapeseed will cause dietary iodine deficiency because it blocks uptake of iodine in gut.
85
Clinical case: goieterism and failure to thirve in kids cont: what could have causes the presence of goiter in kids
Goitrin is compound excreted in milk or passed in utero on to offspring which can cause mass and hypothyroidism
86
What explains the presence of goiters in HPT axis
Goiters is a result of lack of negative feedback from thyroid hormones, so no negative feedback via T3/T4, which will cause increased secretion of TSH and enhance growth of thyroid gland
87
Does the following situation cause goiters: hypothyroidism caused by primary failure of thyroid gland, decreased T3 and T4 levels, increased TSH. Is a goiter present and why
Yes, primary impact to thyroid gland so unable to secrete t3/t4 to act in negative feedback loop to anterior pituitary, so increase TSH released onto thyroid gland causing increased growth of gland
88
Does the following situation cause goiters: hypothyroidism, anterior pituitary defiancy, decreased T3/T4, decreases TSH and/or decreases TRH. Is a goiter present, why or why not?
No goiter, anterior pituitary deficiency means it can’t release TSH. (increased TSH correlates with presence of goiters
89
Will the following situation causer a goiter to be present: hypothyroidism caused by iodine deficiency. Decreased T3/T4 and increased TSH. Is a goiter present, why or why not
Yes, because iodine is only needed to make t3/t4 not needed to release TSH from anterior pituitary so we have excess release of TSH on thyroid gland without negative feedback from t3/t4 therefore enhanced growth of thyroid
90
Would the following situation cause a goiter: hyperthyroidism caused by thyroid-stimulating immunoglobulin: Graves’ disease, increase T3/T4, decreased TSH. Is a goiter present, why or why not
Yes, only scenario where goiter is present and TSH is low because thyroid stimulating immunoglobulin acts like TSH therefore enhancing growth of thyroid
91
Would the following situation cause goiters: hyperthyroidism cause by excess pituitary function, ex: thyrotroph adenoma, increased T3/T4 and increased TSH and/or TRH. Is a goiter present, why or why not
Yes because tumor causes insuppressible release of TSH from pituitary onto thyroid that is not stopped by negative feedback loop so increase TSH will enhance growth of thyroid gland
92
Does the following situation cause goiters: hyperthyroidism caused by hypersecreting thyroid hormone, increased T3/T4 and decreased TSH
No because only thyroid gland is implicated not any upstream signaling so won’t cause increase in TSH, if anything will cause a decrease in TSH release
