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BIOL 432 > Thyroid Hormones > Flashcards

Thyroid Hormones Flashcards

1
Q

thyroid hormones increase…

A

oxygen consumption, basal metabolic rate, and thermogenesis/energy expenditure

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2
Q

thyroid hormones regulate…

A

glucose metabolism - increases hepatic glucose output

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3
Q

thyroid hormones promote…

A

fetal and childhood growth and CNS development

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4
Q

thyroid hormones interact…

A

with many other hormones, affect their production, clearance, and/or effects (eg synergy with GH)

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5
Q

thyroid hormones also have ______ effects

A

cardiovascular, pulmonary, GI, hematopoietic effects

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6
Q

hyperthyroidism

A
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7
Q

hyperthyroidism main symptom

A

weight loss, increased food intake but cannot meet demand of high energy expenditure/metabolic rate

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8
Q

hypothyroidism

A

autoimmune disorder causing under active thyroid

-> ie hashimoto’s disease

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9
Q

hypothyroidism main symptom

A

weight gain due to decreased metabolic rate

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10
Q

how can thyroid hormones be describe?

A

as two linked iodinated tyrosine molecules, cleaved form a large glycoprotein prohormone, thyroglobulin

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11
Q

how is iodine important in thyroid hormones?

A

it is a key structural element of thyroid hormones, so it is an essential micronutrient

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12
Q

what does iodine do?

A

regulates TH production, excess iodine levels inhibit TH production at key steps

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13
Q

what can radioactive iodine be used for?

A

used to treat or diagnose thyroid problems.

  • the tendency of iodine to collect in the thyroid makes it useful for imaging or treatment (radiation emitted by the radioactive iodine destroys the thyroid cells)
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14
Q

are thyroid hormones hydrophilic or hydrophobic?

A

hydrophobic; they require blood binding proteins to travel in circulation

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15
Q

what receptors do thyroid hormones use?

A

nuclear receptors rather than cell surface receptors

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16
Q

what does deoidinase enzyme catalyzed removal of an iodine atom do?

A

either activate or deactivate depending on which I- is removed

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17
Q

what does the thyroid hormone secrete

A

thyroid hormones

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18
Q

what hormone does the thyroid gland primarily secrete?

A

thyroxine, T4

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19
Q

what else does the thyroid gland secrete?

A

T3, but in lesser quantities than T4

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20
Q

what does T3 arise from?

A

deiodination of the outer ring of T4, mostly in peripheral tissues (liver, kidney, skeletal muscle)

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21
Q

T3 is the most ‘metabolically active’, why?

A

it has the highest binding affinity for the nuclear TH receptors

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22
Q

what does reverse T3 (rT3) arise from?

A

deiodination of the inner ring of T4

  • has very short half life,
  • ‘inactive’/no genomic effects
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23
Q

what do different deiodinase enzymes enable?

A

local modulation of TH actions

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24
Q

what is the thyroid gland made up of?

A

many small globular sacs (follicles) that are filled with a fluid called colloid

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25
Q

what are the globular sacs of the thyroid gland called?

A

follicles

26
Q

what is the fluid in the globular sacs of the thyroid gland called?

A

colloid

27
Q

what do follicular cells do?

A

synthesize thyroglobulin and actively take up (trap) iodide

  • these cells are lining the follicles
28
Q

what happens at the apical-colloid interface of the thyroid gland?

A

iodine is oxidized and thyroglobulin is iodinated as it is secreted into the colloid, where it is stored until needed

29
Q

what happens when colloid contents are stimulate by TSH/ are ‘needed’?

A

the colloid contents (including iodinated thyroglobulin) are engulfed by the same or neighbouring follicle cells

  • in these cells, proteolysis/cleavage of thyroglobulin in lysosomes produces T4 and T3, which are released into circulation
30
Q

describe the steps in thyroid hormone synthesis.

A
  1. uptake of iodide (active transport across basement membrane). Iodide needs to be oxidized to be attached to thyroglobulin (TG)
  2. (in parallel) Transcription of TG gene (promoted by TSH)
  3. Translation & modifications of TG prohormone (includes glycosylation post-translational modification in rough ER & Golgi apparatus)
  4. Packaging of TG by Golgi apparatus
  5. Secretion TG into colloid by exocytosis at apical surface of cells
  6. Production of iodinated TG: at apical-colloid interface, tyrosine residues are enzymatically iodinated as it is secreted into colloid, and two iodinated tyrosyl residues in TG are joined
  7. TG with iodinated tyrosines: stored in colloid
  8. Stimulated by TSH, TG is reabsorbed. Lysosomes fuse with the endosomes and TG is degraded; T4 and T3 are released into circulation
    Figure 7-7
31
Q

what do thyrotroph cells in the anterior pituitary release?

A

thyroid stimulating hormone (TSH)

32
Q

what type of hormone is TSH?

A

a glycoprotein

33
Q

what are the effects of TSH on thyroid gland function?

A

stimulates thyroid hormone synthesis and secretion and also causes an increase in thyroid gland size and vascularization

34
Q

what inhibits TSH from thyrotroph cells?

A

somatostatin and thyroid hormone (TH, T3, and T4)

  • thyroid hormone inhibited by a negative feedback loop
35
Q

what stimulates TSH?

A

thyrotropin-releasing hormone (TRH)

36
Q

describe the steps of thyroid hormone regulation.

A

1) Neurons from hypothalamus secrete
thyrotropin-releasing hormone (TRH)
into portal veins that provide a direct route for TRH to the anterior lobe cells

2) Thyrotroph cells in the anterior pituitary are stimulated by TRH to secrete thyroid-stimulating hormone (TSH) into the pituitary venous system; inhibited by somatostatin from hypothalamus

3) Cells in thyroid are stimulated by TSH to secrete thyroid hormone (TH) into the capillaries for transport to target tissues and feed back via bloodstream to hypothalamus and pituitary

4) TH transported into cells of target tissues; Free/unbound T3 is main “metabolically active” form

5a) Negative Feedback: serum T3 and T4 levels negatively regulate TRH and TSH

5b) Negative Feedback: excess iodide inhibits TH production

37
Q

describe hormones in plasma

A

hormones in plasma are either in free form (biologically active) or bound to other molecules (ie blood binding proteins)

38
Q

what do blood binding proteins affect?

A

affect controlled release and stability of hormone pool

39
Q

how do blood binding proteins make the hormone pool more stable?

A

provides reservoir of hormone that exchanges w free hormone fraction

  • more uniform/distant distribution
  • slowing hormone metabolism/breakdown
40
Q

what is an example of how blood binding proteins make the hormone soluble in plasma?

A

thyroid hormones are hydrophobic

41
Q

what are two examples of blood binding proteins?

A
  1. albumins
  2. globulins
42
Q

what are albumins?

A

family of water soluble globular proteins; ie serum albumin

43
Q

describe serum albumin

A
  • produced by the liver
  • the most abundant blood protein in mammals
  • binds to a range of molecules (w varying degrees of affinity) including steroids, fatty acids, and thyroid hormones
44
Q

what are globulins?

A

another family of globular proteins

45
Q

what are the two ways thyroid hormones exert effects?

A

via..

  1. genomic actions (binding to nuclear receptors, therefore regulating gene expression)
  2. non-genomic actions (interacting w enzymes or other cellular proteins)
46
Q

how is TH transported into target cells?

A

by specific carriers/transporter proteins

47
Q

in the cytoplasm, THs are…

A

bound to cytoplasmic binding proteins; and much of the T4 is converted by deiodinase enzyme to T3

48
Q

THs diffuse into the nucleus to bind to…

A

thyroid receptors, which are often already bound to DNA (receptors have greater affinity for T3)

49
Q

what do thyroid receptors bind to?

A

to response elements as heterodimer

50
Q

what do TR’s bind with and what does the interaction with thyroid hormone cause?

A

preferentially with retinoid X receptor (RXR); interaction w TH causes a conformational change leading to activation or suppression of target genes

51
Q

what is TRE?

A

thyroid hormone response elements; TRs bind to a large variety of TREs

52
Q

what are the three domains for thyroid hormones?

A
  • amino terminal domain
  • DNA-binding domain
  • ligand binding domain (at C terminal)
53
Q

what does the amino terminal domain do?

A
  • ligand independent transactivation
54
Q

what does the DNA binding domain do?

A
  • DNA binding
  • DNA dimerization
55
Q

what does the ligand binding domain do?

A
  • hetero and homo dimerization
  • ligand binding -> domain that binds TH; highest affinity for T3
  • ligand dependent transactivation
  • nuclear translocation
56
Q

what characterizes the inactive receptor homo or heterodimer?

A

T3R/RXR, T3R
- compressor complex: eg histone deacetylases (HDACs) close chromatin, repressing transcription of gene

57
Q

what characterizes the active receptor heterodimer

A

T3
- eg co activators can recruit histone acetyltransferase (HATs) open chromatin for transcription, co-activator complex (bridging to transcription complex, stabilizing)

58
Q

what is TR-alpha and TR-beta?

A

2 separate genes w distinct expression and activation patterns

59
Q

what do thyroid hormones increase?

A

oxygen consumption, basal metabolic rate, and thermogenesis/energy expenditure

60
Q

what do thyroid hormones regualte?

A

glucose metabolism

61
Q

how do thyroid hormones regulate glucose metabolism?

A
  • enhance glucose absorption in gut
  • promote glycogen synthesis and glucose output by liver
  • affect insulin and glucagon levels, and insulin resistance in target tissues

BIOL 432 (19 decks)

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