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ANAT322 > Neuroendocrine Regulation of Thyroid Function > Flashcards

Neuroendocrine Regulation of Thyroid Function Flashcards

1
Q

where is TRH synthesized? where is it secreted?

A

in parvocellular neurons of the PVN. secreted at the anterior pituitary.

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2
Q

where is TSH secreted from? what does it do?

A

secreted from anterior pituitary onto the thyroid gland to increase T4 and T3 thyroid hormones synthesis

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3
Q

what is T3 and T4’s effect on TRH?

A

inhibits TRH and TSH secretion (classic negative feedback)

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4
Q

what vessel does the hypothalamus receive blood from?

A

hypothalamic artery. sends direct arterial blood

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5
Q

what vessel does the anterior pituitary recieve blood from?

A

superior hypophyseal artery. sends venous blood)

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6
Q

examples of hormones released directly in the neurohypophysis?

A

oxytocin, arginine vasopressin

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7
Q

where in the PVN are TRH producing hormones located?

A

medially

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8
Q

what neurons project to the median eminence?

A

only the parvocellular neurons of the PVN

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9
Q

describe TRH structure

A

three-amino acid neuropeptide

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10
Q

what is the main driver of T4 synthesis?

A

TRH! not TSH

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11
Q

what is the main TRH negative regulator?

A

T3

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12
Q

how does T3 act as a negative regulator?

A

genomically and post-genomically: increases expression of TRH peptidase at the nerve ending (post-translational)

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13
Q

what is TSH necessary for?

A

normal glycosylation of TSH at post-translational level

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14
Q

why does hypothalamus injury cause low TSH?

A

without TRH action, anterior pituitary can’t produce as much TSH, and it lacks the post-translational glycosylation

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15
Q

what happened when they implanted T4 close to medial parvocellular PVN neurons?

A

decreased expression of TRH gene!

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16
Q

difference between T4 and T3?

A

T4 is the pro-hormone for T3

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17
Q

name the neurohypophysis (anterior pit) hormones

A

go look for that adenoma please Micheal
GH
LH
FSH
TSH
ACTH
prolactin
MSH

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18
Q

what is different between individuals relating to TSH/T4,T3 levels?

A

the set point varies between people

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19
Q

what do each glycoproteins have in common? name the glycoproteins

A

same alpha subunit, different beta subunit that determine interaction with receptor.
FSH, LH, CG, TSH

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20
Q

describe TSH structure

A

glycoprotein with 2 chains with CHO moiety, essential for biological activity

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21
Q

what does separation of the TSH chains cause?

A

inactivation of TSH

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22
Q

what receptor does TSH bind to?

A

G-protein coupled receptor

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23
Q

how is TSH secreted?

A

circadian rhythm; pulsatile secretions

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24
Q

what is different about the anterior pituitary’s TH receptor occupancy status? (THR in TSH producing cells)

A

over half are occupied by T3 that is derived from local intracellular T4

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25
what "holds back" TSH secretion/linearly correlates with with TSH suppression?
nuclear T3
26
what level of TS receptors occupancy is needed to keep TSH levels normal?
high level of occupancy
27
how are thyroid cells organized?
in follicles: spherical hollow arrangements of epithelial cells
28
what are colloids?
it's in the thyroid gland follicles, composed of thyroglobulin
29
what is thyroglobulin?
protein in which TH are synthesized and stored until released. serves as a template for TH synthesis
30
what and where are C cells found?
between follicles in thyroid gland, they produce calcitonin and release in capillary network
31
in what circumstances can you feel the thyroid gland?
when someone has a goiter (enlarged thyroid gland)
32
what is the difference between T3 and T4?
T3 lacks the iodine at the 5" position of the outer ring
33
where is thyroglobulin produced and stored?
produced in thyrocyte, stored in follicles
34
what residues are sparsely spaced in thyroglobulin? they create what sites?
tyrosine residues create hormonogenic sites (TH production)
35
do all tyrosine residues on thyroglobulin participate in TH formation?
no
36
first step of TH biosynthesis
iodide uptake -> inorganic iodide anion gets oxidized to diatomic iodine -> gets covalently linked to tyrosyl residues -> tyrosine
37
how many MIT/DIT are needed to produce T3 and T4?
1 MIT + 1 DIT = T3 2 DITs = T4
38
how is iodide transported in the cell if the I conc inside > outside?
through the NIS: N & I symporter
39
2nd step of TH biosynthesis?
coupling of iodinated tyrosines (MIT + DIT)
40
how are TH released from the colloid (where they are stored in thyroglobulin)?
via endolysosomes. diffused into the blood
41
what are TSH effects? what does it act on the fastest?
- earliest effect = release of TH (Tg endocytosis, digestion & release of iodoaminoacids) - also stimulates synthesis (NIS, I oxidation & organification, iodotyrosines coupling, TG synthesis)
42
where is most of T3 coming from?
liver, muscles, kidney where T4 is converted to T3. only a small portion is from anterior pituitary.
43
what can T4 be converted to with what enzymes?
D1, D2 -> converts to T3 D1, D3 -> converts to reverse T3 (inactivate T4)
44
what dictates T4 conversion (activation or inactivation)?
T4 levels! (too high = hyperthyroidism = converts to reverse T3 = inactivates / too low = hypothyroidism = converts to T3 = activate)
45
___ is about 10x more abundant than ___ at the nuclear receptor level
T3 is 10x more abundant than T4
46
___ is 10x more potent than ___
T3 is 10x more potent than T4
47
what happens to thyroxine, T3, and TSH levels as hypothyroidism gets worst?
thyroxine decreases, T3 stays somewhat constant, TSH increases
48
how does T3 level stay constant even with a failing thyroid gland?
peripheral conversion of T4 to T3 is replaced by thyroidal secretion of T3. -> because increased TSH stimulates D2 in the thyroid which increase T3
49
what happens to T4 and TSH levels with hypothyroidism?
decrease in T4, increase in TSH
50
what happens to T4 in astrocytes?
converts to T3 via D2 and either binds to nuclear receptor OR exits cell and access neuron to bind to nuclear receptor there or gets inactivated by D3
51
what can someone with intense hypothyroidism do to protect his brain?
increase D2, decrease D3, upregulated T4 and T3 transport proteins
52
how is facultative adaptive thermogenesis linked to thyroid?
T3 increases UCP1 action (uncouples ATP production of smtg so all the energy is lost as heat -> increases thermogenesis
53
do we need to be hyperthyroidism to use the adaptive thermogenesis? because T3 increases it?
no, because D2 converts T4 to T3 locally
54
where does this thermogenesis happen?
in brown adipose tissue
55
symptoms of hyperthyroidism
- weight loss in spite of increased appetite - increased sweating from dissipating heat - anxiety and sleeplessness
56
what causes increase in sweating during hyperthyroidism?
increase in energy expenditure and basal thermogenesis
57
how does leptin affect hypothalamic pituitary thyroid axes?
it upregulates the axis (shown by T4 serum increase)
58
what is leptin's effect at hypothalamus?
inhibits AgRP/NPY secretion (inhibits orexigenic), stimulates hypothalamic-pituitary-thyroid axes to activate BAT thermogenesis
59
what is somatostatin's neurons effect on TSH production?
negative effect on TRH action
60
what is dopaminergic neurons effect on TSH production?
inhibits TSH gene expression at nucleus, but stimulates TRH production
61
what increase (?) the TSH:T4 ratio in individuals?
- TRH - Increased leptin - adrenergic - CART
62
what decreases (?) the TSH:T4 ratio in individuals?
- Glucocorticoids - Reduced leptin - Dopamine - Somatostatin - Cytokines (TNF-a) - NFkB-induced D2 expression
63
symptoms of hypothyroidism
- Sensitivity to cold - Weight gain despite decreased appetite
64
in what cases is TSH pulsatility lost?
in people with pituitary tumors
65
what is acromegaly?
distal growth. anabolic state -> everything is diverted to glucose metabolism
66
what do elevated somatostation levels cause?
they decrease TSH secretion
67
how does a heart attack affect thyroid hormones?
acute (right after) = normal TSH, normal T4, decreased T3 and increased rT3 because of decreased D1 and increased D3. chronic (72h after)
68
why does the acute phase happen?
high D3, low D1, low T3 to overcompensatw
69
how is the affinity of T3 vs T4 with nuclear receptor?
T3 has 10x affinity than T4

ANAT322 (10 decks)

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