Lecture 19 2/22/24 Flashcards

1
Q

What are the characteristics of iodide and the iodide pump?

A

-taken up from blood
-pumped into cell cytoplasm via iodide pump
-iodide pump co-transports Na+ and I- into cell
-pump is TSH sensitive
-Na+/K+ ATPase pumps Na+ out of cells to maintain gradient

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2
Q

What are the characteristics of thyroglobulin?

A

-produced by follicular cells
-contains high number of tyrosine molecules

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3
Q

What is the role of thyroid peroxidase?

A

-oxidizes iodide to elemental iodine
-iodine binds to the tyrosine residues of thyroglobulin

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4
Q

How does MIT differ from DIT?

A

-MIT occurs when thyroglobulin is iodinated only in position 3’
-DIT occurs when thyroglobulin is iodinated in both 3’ and 5’ positions

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5
Q

What molecule results from two DIT molecules joining together?

A

T4

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6
Q

What molecule results from one DIT molecule and one MIT molecule joining together?

A

T3

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7
Q

What leads to the liberation of T4 and T3?

A

-stimulation of thyroid follicular cells via TSH to produce hormones
-endocytosis and proteolysis of iodinated thyroglobulin

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8
Q

What are the two main regulation mechanisms for thyroid hormone synthesis and secretion?

A

-an “autoregulation” mechanism which reflects available iodine levels
-regulation by the hypothalamus and anterior pituitary

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9
Q

How do iodide levels influence iodide transport into follicular cells?

A

-low iodide levels increase iodide transport into cells
-high iodide levels decrease iodide transport into cells
-negative feedback loop

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10
Q

What are the characteristics of thyrotropin-releasing hormone (TRH)?

A

-hypothalamic releasing factor
-tripeptide hormone
-secreted in hypophyseal portal system
-target thyrotropes in the anterior pituitary that have TRH receptors
-2-6 minute half-life

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11
Q

Why does TRH have a short half-life?

A

because it is a tripeptide

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12
Q

What are the characteristics of thyroid-stimulating hormone (TSH)?

A

-produced by thyrotropes in anterior pituitary
-glycoprotein hormone
-targets thyroid follicular cells
-75-80 min. half-life

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13
Q

What are the components of TSH?

A

-alpha subunit that is common to LH, FSH, and TSH
-beta subunit that varies to determine receptor specificity and biological activity

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14
Q

What are the functions of TSH?

A

-increase iodide transport into follicular cells
-increase thyroglobulin production and iodination
-increase endocytosis of colloid

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15
Q

What influences the release of TSH?

A

-hypothalamic TRH
-thyroid hormones

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16
Q

What are the consequences of the thyroid hormones exerting negative feedback on TSH?

A

-inhibition of TSH synthesis
-decrease in pituitary receptors for TRH

17
Q

How does T4 compare to T3?

A

-majority of secreted thyroid hormones is T4
-T4 has a longer half-life than T3

18
Q

Why is it important that the thyroid gland contains a sufficient high level of T4?

A

the body can go 4-8 weeks without synthesis of new hormones

19
Q

Which hormones are the only ones that are critically inhibited by nutritional deficiency?

20
Q

Where is the majority of iodine excreted?

21
Q

Where is iodine trapped besides the urine?

A

-gastric mucosa
-salivary glands

22
Q

What are the characteristics of thyroid hormone transport?

A

-hormones are lipid-soluble/lipophilic
-less than 1% is free in circulation
-only the free portion is biologically available to the tissues

23
Q

Which plasma proteins bind T3 and T4?

A

-thyroxine-binding globulin
-thyroxine-binding pre-albumin
-albumin

24
Q

What is the mechanism of action of T3?

A

-thyroid hormone receptors have a greater affinity for T3 than T4
-conversion of T4 to T3 is activation step
-receptor/hormone complex binds to TRE/thyroid response element
-binding results in changes in gene transcription

25
Where does conversion of T4 to T3 occur?
in the cytosol of target cells of peripheral tissues
26
Which enzyme is responsible to T4 to T3 conversion?
iodothyronine deiodinase
27
Why is it important that the iodothyronine deiodinase enzymes contain selenium?
selenium deficiency can reduce activity
28
What are the characteristics of T4 and T3 in fetal life?
-T4 and T3 affect both growth and differentiation -fetus depends on its own T4; thyroid hormones do not cross placenta -CNS in fetus is highly sensitive to thyroid hormones; up to 2 years
29
How do thyroid hormones, growth hormone, and androgens/estrogens impact human growth and development?
from birth to age 20: -thyroid hormones are most important at a young age and taper off -growth hormone is important throughout -androgens/estrogens are important around puberty age (10-20)
30
What are the effects of thyroid hormones on growth and development?
-increased bone growth/maturation -increased tooth development and eruption -increased rate/force of skeletal muscle contraction -increased growth/maturation of epidermis, hair follicles, nails -inhibited synthesis and increased degradation of mucopolysaccharides in subcutaneous tissue
31
What is the major target gene of T3?
Na+/K+ ATPase pump
32
What are the effects of T3 on metabolism?
-increases synthesis of Na+/K+ ATPase pumps, increasing ATP consumption -acts on mitochondria to increase ATP synthesis -increased basal metabolic rate and increased thermogenesis -increased RBC mass -increased oxygen dissociation from hemoglobin
33
What are the consequences of excess T3/T4?
-increased breakdown in adipose tissue -increased breakdown in proteins/muscle wasting -increased glycogenolysis -increased glucose absorption from GI tract -increased carb. turnover -down-regulation of insulin receptors -increased substrate availability
34
What are the effects of T3/T4 on the neuromuscular system?
-critical for normal CNS neuronal development -enhances wakefulness/alertness -enhances memory/learning capacity -required for normal emotional tone -increases speed and amplitude of peripheral nerve reflexes
35
What are the effects of T3/T4 on the cardiovascular system?
-up-regulates catecholamine beta receptors, increasing sympathetic tone -increased heart rate -increased stroke volume -increased cardiac output -increased myosin conc. -increased force of cardiac contractions -increased BP
36
What are the effects of T3/T4 on the respiratory system?
-increases resting resp. rate -increases minute ventilation -increases ventilatory response to hypercapnia and hypoxia
37
What are the effects of T3/T4 on the renal system?
-increases blood flow -increases glomerular filtration rate -leads to polyuria/polydipsia
38
What are the effects of T3/T4 on the repro. system?
-required for normal follicular dev. and ovulation -required for normal pregnancy maintenance -required for normal spermatogenesis