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?

A

T3 and T4

20
Q

Where is the majority of iodine excreted?

A

urine

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
Q

Where does conversion of T4 to T3 occur?

A

in the cytosol of target cells of peripheral tissues

26
Q

Which enzyme is responsible to T4 to T3 conversion?

A

iodothyronine deiodinase

27
Q

Why is it important that the iodothyronine deiodinase enzymes contain selenium?

A

selenium deficiency can reduce activity

28
Q

What are the characteristics of T4 and T3 in fetal life?

A

-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
Q

How do thyroid hormones, growth hormone, and androgens/estrogens impact human growth and development?

A

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
Q

What are the effects of thyroid hormones on growth and development?

A

-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
Q

What is the major target gene of T3?

A

Na+/K+ ATPase pump

32
Q

What are the effects of T3 on metabolism?

A

-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
Q

What are the consequences of excess T3/T4?

A

-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
Q

What are the effects of T3/T4 on the neuromuscular system?

A

-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
Q

What are the effects of T3/T4 on the cardiovascular system?

A

-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
Q

What are the effects of T3/T4 on the respiratory system?

A

-increases resting resp. rate
-increases minute ventilation
-increases ventilatory response to hypercapnia and hypoxia

37
Q

What are the effects of T3/T4 on the renal system?

A

-increases blood flow
-increases glomerular filtration rate
-leads to polyuria/polydipsia

38
Q

What are the effects of T3/T4 on the repro. system?

A

-required for normal follicular dev. and ovulation
-required for normal pregnancy maintenance
-required for normal spermatogenesis