Thyroid Hormones Flashcards

1
Q

which thyroid hormone is dominant?

A

T3- 85% of thyroid hormone bound to thryoid receptor is T3

T3 has a 10x greater affinity for TR than T4

many peripheral tissues convert T4 into T3 for their use

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2
Q

describe the thyroid receptor

A

TR is in the nucleus, and thyroid hormone binds there directly (as a dimer w/ RXR or RAR)

their are 2 subtypes- alpha and beta, coded for by 2 different genes

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3
Q

thyroid response element

A

the coding sequence on the genome where the TR binds

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4
Q

what changes does the binding of TH cause in the cell?

A

increases mRNA transcription

unbound HR causes transcription inhibition (ie not inert)

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5
Q

symptoms of hypothyroidism

A
weakness
dry skin
coarse skin
lethargy
slow speech
edema of eyelids
sensation of cold
reduced sweating
cold skin
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6
Q

symptoms of hyperthyroidism

A
nervousness
increased sweating
intolerance to heat
palpitations
fatigue
weight loss
tachycardia
dyspnea
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7
Q

most common cause of hyperthyroidism

A

graves disease- autoimmune

goiter, eye symptoms, and hyperthyroidism

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8
Q

describe the physiologic effects of TH

A

metabolic

  • basal metabolic rate
  • heat production
  • water/ion transport
  • calcium and phosphorus metabolism
  • cholesterol and fat metabolism
  • nitrogen turnover
  • increases GI tract activity
  • increases CV (HR) and respiratory

all above is reversible w/ replacement therapy

growth and development

  • growth of tissues
  • development and maturation of CNS

these are not reversible changes

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9
Q

describe lack of TH during development (hypothyroidism)

A
  • impaired brain development
  • limited growth
  • ataxia
  • spastic muscles
  • deafness

not reversible

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10
Q

what is the outcome like for people born w/ congenital hypothyroidism and receive adequate replacement therapy immediately?

A

seemingly normal

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11
Q

how does the fetus receive TH?

A

the mother supplies TH to the fetus until they are able to make it themselves

if the mother TH is inadequate and untreated, it often leads to infertility

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12
Q

most important cause of preventable mental defects in the world

A

iodine deficiency

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13
Q

neurological cretin

A

people who do not receive TH from their mother d/t iodine insufficiency

how?

with low iodine supply in the mother, thyroid shifts primarily to T3. T4 is better at crossing the placenta and better at reacting w/ brain. fetus lacks this.

causes:
major CNS damage
fetal thyroid function is impaired, but could be restored w/ iodine postnatally

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14
Q

hypothyroid goiter

A

thyroid cannot make thyroid hormone properly, (iodine deficiency), so no feedback on TSH, which gets continuously secreted and causes growth in the thyroid

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15
Q

hyperthyroid goiter

A

graves disease- autoAb binds the TH continuously and causes growth

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16
Q

which form of TH is essential for fetal development?

A

t4- it crosses the placenta

17
Q

Pax8 mice

A

born w/o Pax8 gene, which is essential for thyroid growth. therefore no thyroid

appear normal at birth:
growth is retarded
poor coordinatoin
deaf
poor hair growth
do not survive beyond weaning
18
Q

do unliganded TR have effects?

A

yes- negative inhibitory effects

19
Q

describe biosynthesis of TH

A

iodide gets concentrated inside follicular cells inside the thyroid

tyrosine residues in thyroglobulin take up one or two iodides to form monoiodotyrosine or diiodotyrosine.

coupling of these molecules forms T3 or T4, w/ T3 favored.

hydrolysis of thyroglobulin yields T4 and T3 (and MIT and DIT)

T3 and 4 are released into the blood

MIT and DIT are retained in the thyroid and deiodinated

20
Q

thiouracil, methimazole

A

inhibit conversion to iodine and creation of MIT and DIT

21
Q

is iodide trapping energy dependent?

A

yes

22
Q

5’deiodinases

A

convert T4 to T3 in periphery

23
Q

perchlorate, thiocyanate

A

inhibit iodide trapping

24
Q

describe the control of TH release

A

-excess dietary iodine suppresses synthesis and release of TH (independent of TSH). likewise, decrease in plasma iodine results in increased uptake.

TSH- main physiological regulator

pathological examples

  • thyroid stimulating ABs
  • TSH binding- inhibiting Abs
  • hCG (stimulates)
25
Q

describe TSH synthesis and secretion

A

controlled by TRH from anterior hypothalamus. stored in median eminence

feedback from thyroid hormones at hypothalamus and pituitary

the TSH-a/b genes contain TREs that are inhibitory

T3 downregulates the TRH receptors in pituitary

26
Q

how does TSH exert its effects on the thyroid?

A

activates cyclic AMP

increases iodine metabolism, hormone synthesis, vascularity, size, etc.

the first noticable change of TSH administration is an increase in TH secretion

27
Q

how does TRH mediate its effects on anterior pituitary

A

PIP2 - IP3 - PKC pathway results in TSH release

28
Q

THs are bound by plasma proteins. what are the major carriers? which one is bound more?

A

the three binding proteins are:

thyroxine binding globulin
thyroxine binding prealbumin (only T4)
albumin

T4 binds more than T3, but the free levels are comparable. However, there is much more T4 in the blood, and because it binds so well, it has a long half life

29
Q

what are the TH transporters?

A

MCT family (MCT 8, 10)

OATP family

30
Q

describe activation of T4

A

5-deiodinases remove an iodine from the outer ring to generate T3

type 1: thyroid liver kidney. major role to deiodinate rT3

type 2: brain, brown fat, pituitary, uterus. most important enzyme

31
Q

describe deactivation of T4 and T3

A

deiodinase removes an iodine from the inner ring to yield rT3 and 3,3-T2 respectively

this is type 3 deiodinase (brain, uterus, placenta)

32
Q

20% of iodine in T3 and T4 is eliminated how?

A

feces