Lec 23 Endocrine Intro Flashcards

1
Q

Is set point constant across stimuli?

A

No - it is specific for particular stimuli and particular situations

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2
Q

What did Charles Edouard Brown Sequard show

A

concept of hormonal action

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3
Q

3 functions of endocrine system

A
  • homeostasis
  • growth and development
  • reproduction
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4
Q

Where are neuropeptides synthesized?

A

in nerve cell body

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5
Q

Where do hypothalamic neuropeptides go/target?

A
  • into vessels of hypothalamic-pituitary portal system
  • transported to target cells in anterior pituitary
  • tells anterior pituitary to make/secrete its hormones
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6
Q

What are trophs?

A

endocrine cells of anterior pituitary

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7
Q

What do lactotrophs secrete?

A

prolactin

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8
Q

what do somatotrophs secrete?

A

growth hormone

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9
Q

what do corticotrophs secrete?

A

ACTH

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10
Q

What do thyrotrophs secrete?

A

TSH

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11
Q

Where do posterior pituitary hormones come from?

A
  • they are made in hypothalamus and stored in bulbous nerve terminals in posterior pituitary
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12
Q

what hormones are made in posterior pituitary?

A

none

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13
Q

What 2 hormones are secreted via posterior pituitary?

A

vasopressin [ADH]

oxytocin

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14
Q

If you took out the pituitary would you still be able to secrete vasopressin?

A

yes!

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15
Q

What are 3 classes of hormones

A
  • polypeptides
  • amino acid derivatives
  • thyroid hormones and steroids
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16
Q

Are polypeptide hormones lipid soluble? where is receptor located on/in cell? example?

A
  • not lipid soluble
  • bind to receptors on surface of target cell
  • ex: pituitary hormones
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17
Q

Are amino acid derivative hormones lipid soluble? where is receptor located on/in cell? example?

A
  • most are not lipid soluble
  • bind to receptors on surface of target cell
  • ex. epinephrine
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18
Q

Are thyroid hormones lipid soluble? where is receptor located on/in cell?

A
  • YES! they act like steroid hormones

- bind to receptor inside target cell

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19
Q

Are steroid hormones lipid soluble? where is receptor located on/in cell? example?

A
  • they are lipid soluble
  • bind to receptors inside target cell
  • ex. cortisol
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20
Q

6 peptide hormones secreted by anterior pituitary?

A
  1. LH: luteinizing hormone
  2. FSH: follicle stimulating hormone
  3. GH: growth hormone
  4. prolactin
  5. TSH: thyroid stimulating hormone
  6. ACTH: adrenocorticotropic hormone
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21
Q

What organ do LH and FSH target? What effect on target?

A

ovary/testes

  • FSH causes ovary to secrete estrogen
  • LH causes testes to secrete testosterone
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22
Q

What organ does prolactin target? What effect on target?

A

breasts

- causes lactation [make milk]

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23
Q

What organ does GH target? What effect on target?

A

liver

- causes liver to secrete IGF-1 [insulin like growth factor 1]

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24
Q

What organ does TSH target? What effect on target?

A

thyroid

- causes thryoid to secrete thyroxine [T4]

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25
Q

What organ does ACTH target? What effect on target?

A

adrenal glands

- causes adrenals to secrete cortisol

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26
Q

What organ does ADH target? What effect on target?

A

kidney

- antidiuretic, causes reabsorption of water in kidney

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27
Q

What is effect of estrogen on FSH?

A

turns off FSH = negative feedback

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28
Q

What is effect of testosterone on LH?

A

turns off LH = negative feedback

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29
Q

What is effect of thyroxine on TSH?

A

turns off TSH = negative feedback

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30
Q

Which of the pituitary hormones do not have negative feedback from their target organs?

A
  • only prolactin
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31
Q

What kind of feedback loop in prolactin?

A
  • sucking on breast increases prolactin secretion

= positive feedback

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32
Q

What stimulates TSH secretion from AP?

A

TRH from hypothalamus

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33
Q

What stimulates ACTH from AP?

A

CRH from hypothalamus

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34
Q

What stimulates LH from AP?

A

GnRH from hypothalamus

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35
Q

What stimulates FSH from AP?

A

GnRH from hypothalamus

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36
Q

What does somatostatin do to anterior pituitary? where does it come from?

A
  • released from hypothalamus

- inhibits anterior pituitary secretion of growth hormone

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37
Q

What does dopamine do to anterior pituitary? where does it come from?

A

released from hypothalamus

inhibits prolactin secretion

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38
Q

What are the 4 trophic releasing hormones from the hypothalamus and their targets

A

1 TRH –> TSH
2 CRH –> ACTH
3 GnRH –> LH + FSH
4 GHRH –> GH

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39
Q

What makes a cell a target cell?

A

specific receptors for the hormone

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40
Q

What causes down regulation/up regulation?

A
  • receptor number on target cell

- affinity of target cell receptor for hormone

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41
Q

Severed stock experiment – continuous vs pulsatile? what explains this

A
  • continuous infusion of GnRH down regulates LH/FSH
  • pulsatile infusion increases LH/FSH
  • with continuos infusion you are continuously having GnRH bound which when bound brings the receptor into cell and degraded. so in contuous activation you are degrading the receptors and lowering the number = down regulation
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42
Q

When is cortisol highest? lowest?

A
  • highest in AM

- lowest in PM

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43
Q

When is growth hormone highest?

A

peak at night, within an hour of sleepish

lower during day time

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44
Q

What does testosterone peak?

A

morning

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45
Q

What is relation GH and insulin?

A

GH is counter-regulatory to insulin

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46
Q

Is major hypothalamic control of prolactin stimulatory or inhibitory? by what?

A

inhibitory – by dopamine

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47
Q

What is relation GH and somatostatin?

A

somatostatin from hypothalamus inhibits GH from AP

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48
Q

What are 2 effects of growth hormone

A
  • direct action on metabolism

- stimulation IGF-1 from liver

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49
Q

What other hormone is in same family as growth hormone?

A

prolactin

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50
Q

What is shared in prolactin/GH family? type of Receptor?

A
  • dimer receptor
  • tyrosine kinase associated receptor
  • activates Jak/stat pathway in cell
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51
Q

What is different insulin receptor vs growth hormone receptor

A
  • insulin receptor: 2 beta subunits bound 2 alpha subunits bound to each other, tyrosine kinase is part of the receptor
  • growth hormone receptor: 2 separate subunits
52
Q

What types of hormones use JAK-STAT signaling pathway?

A
  • growth hormone
  • prolactin
  • erythropoietin
  • thrombopoietin
53
Q

What is characteristic of jak/stat signalling pathway

A
  • 2 separate pieces of receptor
  • jak binds both receptor and Stat = signal transducer
  • stat transduces signal into nucleus
54
Q

Where does grhelin come from? where does it act [2 things]?

A

comes from stomach

  • stimulates GH
  • feedback to NPY [feed me] neurons from hypothalamus
55
Q

3 Direct actions of GH hormone

A
  • increase gluconeogensis in liver
  • increase lypolysis
  • causes liver to secrete IGF1
56
Q

What are 4 [2 things, 2 hormones] positive stimuli of GH?

A
  • puberty
  • working out
  • GHRH
  • Ghrelin
57
Q

What are 3 [2 things, 1 hormone] neg stimuli of GH?

A

obesity
senescence
somatostatin [SRIF]

58
Q

what does IGF1 do?

A
  • growth factor for muscle
  • major growth factor for bone and strength
  • —- activates osteoblasts, blocks osteoclasts
59
Q

How do GH and IFG-1 work together?

A

GH mobilizes substrate [sugar, fat, protein via lypolysis, gluconeogenesis]
IGF-1 incorporates it for growth

60
Q

What makes a cell a target cell?

A

specific receptors for the hormone

61
Q

What causes down regulation/up regulation?

A
  • receptor number on target cell

- affinity of target cell receptor for hormone

62
Q

Severed stock experiment – continuous vs pulsatile? what explains this

A
  • continuous infusion of GnRH down regulates LH/FSH
  • pulsatile infusion increases LH/FSH
  • with continuos infusion you are continuously having GnRH bound which when bound brings the receptor into cell and degraded. so in contuous activation you are degrading the receptors and lowering the number = down regulation
63
Q

When is cortisol highest? lowest?

A
  • highest in AM

- lowest in PM

64
Q

When is growth hormone highest?

A

peak at night, within an hour of sleepish

lower during day time

65
Q

What does testosterone peak?

A

morning

66
Q

What is relation GH and insulin?

A

GH is counter-regulatory to insulin

67
Q

What does HCG do?

A
  • stimulates TSH receptor on thyroid [taking place of TSH] so you get more T3/T4 but low TSH
  • hyperthyroidism
  • in pregnancy
68
Q

What is relation GH and somatostatin?

A

somatostatin from hypothalamus inhibits GH from AP

69
Q

What are 2 effects of growth hormone

A
  • direct action on metabolism

- stimulation IGF-1 from liver

70
Q

What other hormone is in same family as growth hormone?

A

prolactin

71
Q

What is shared in prolactin/GH family? type of Receptor?

A
  • dimer receptor
  • tyrosine kinase associated receptor
  • activates Jak/stat pathway in cell
72
Q

What is different insulin receptor vs growth hormone receptor

A
  • insulin receptor: 2 beta subunits bound 2 alpha subunits bound to each other, tyrosine kinase is part of the receptor
  • growth hormone receptor: 2 separate subunits
73
Q

What types of hormones use JAK-STAT signaling pathway?

A
  • growth hormone
  • prolactin
  • erythropoietin
  • thrombopoietin
74
Q

What is characteristic of jak/stat signalling pathway

A
  • 2 separate pieces of receptor
  • jak binds both receptor and Stat = signal transducer
  • stat transduces signal into nucleus
75
Q

Where does grhelin come from? where does it act [2 things]?

A

comes from stomach

  • stimulates GH
  • feedback to NPY [feed me] neurons from hypothalamus
76
Q

3 Direct actions of GH hormone

A
  • increase gluconeogensis in liver
  • increase lypolysis
  • causes liver to secrete IGF1
77
Q

What are 2 positive stimuli of GH?

A
  • puberty

- working out

78
Q

What are 2 neg stimuli of GH?

A

obesity

senescence

79
Q

what does IGF1 do?

A
growth factor for muscle
binds binding proteins in circulation
major growth factor for bone and strength
act to activate osteoblasts
blocks osteoclasts
80
Q

How do GH and IFG-1 work together?

A

GH mobilizes substrate [sugar, fat, protein via lypolysis, gluconeogenesis]
IGF-1 incorporates it for growth

81
Q

what is tonic inhibition? ex of AP hormone under tonic inhibition?

A
  • most of the time we are under inhibition by default

- prolactin by dopamine

82
Q

What 2 things cause increase in prolactin?

A
  • pregnancy

- breast feeding

83
Q

What is action of ghrelin?

A
  • hunger hormone
  • when food comes in it is stimulated
  • it stimulates GH
84
Q

What are the two hormones of thyroid? which is largest quantity? which is most active? which is used to measure thyroid function?

A

T4 [thyroxine]: largest quantity, used to measure thyroid function

T3 [triiodothyroxine]: most active

85
Q

What is effect of T4/T3 on TSH?

A

inhibits TSH release from AP

86
Q

What 4 things are in glycoprotein hormone family?

A
  • TSH
  • FSH
  • LH
    HCG
87
Q

What is same vs unique in glycoprotein hormones?

A
  • two peptide subunits

- identical alpha, unique beta chains

88
Q

What does HCG do?

A

stimulates TSH receptor on thyroid so you get more T3/T4 but low TSH
in pregnancy

89
Q

Why is glycosylation of TSH important? why can it be falsely measured as high in our blood assays?

A
  • glycosylation of TSH is needed to convey specificity for its receptor
  • improperly glycosylated TSH will not bind to receptor and have action
  • clinically we can measure it and think its ok but it might not be functional –> may have normal TSH level but not internalized/functioning/etc
90
Q

What is situation when you could have normal TSH but hypothyroidism?

A

clinically we can measure TSH levels and see its normal but it might not necessarily be functional/glycosylated
if have sick pituitary it might put out messed up TSH that doesnt work
so we have normal TSH LEVEL but not function
and very low T4/T3 [hypothyroidism]

91
Q

What is action of TSH?

A
  • thryoid cell growth and differentiation
  • hromone synthesis

via cAMP

92
Q

What percentage T4 vs T3?

A

80% T4, 20% T3

93
Q

What is major circulating hormone? why?

A

T4 - produced in large quantity, and long 1/2 life

94
Q

Where does T3 come from?

A
  • directly from thyroid

- converted from T4 in tissue, allows tissue specificty – tissues can decide if they need it

95
Q

Where in thyroid are T3/T4 made?

A

in thyroid colloid

96
Q

What is contained in thyroid colloid?

A

thyroglobulin

97
Q

What are the steps of T3/T4 formation?

A
  1. TG synthesis in follicular cell
  2. I transported into basolateral side of follicular cell via Na-I cotransport
  3. I enters follicular lumen and oxidized to I2 [iodine] by thyroid peroxidase
  4. I2 binds tyr residues on TG to form MIT and DIT by thryoid peroxidase
  5. MIT and DIT couple to for T3 and T4 by thryroid peroxidase
  6. TG endocytosed into follicular cell at stimulation from TSH
  7. T3 and T4 hydrolyzed in lysosomes and enter circulation by proteases
  8. residual MIT and DIT deiodinized and recycled by deiodinase
98
Q

Where is TG [thyroglobulin] synthesized?

A

in follicular cell

99
Q

What brings I into follicular cells?

A

Na I cotransport

100
Q

What 2 things inhibit Na I cotransporter in thyroid?

A
  • perchlorate

- thiocyanate

101
Q

What 3 things does thyroid peroxidase do?

A
  • oxidation I –> I2 [iodide to iodine]
  • binding I2 to tyr residue of TG to make MIT / DIT
  • coupling MIT and DIT to T3 [or two DIT to T4]
102
Q

What does PTU [propylthiouracil] inhibit?

A

it inhibits thyroid peroxidase

  • oxidation I –> I2 [iodide to iodine]
  • binding I2 to tyr residue of TG to make MIT / DIT
  • coupling MIT and DIT to T3 [or two DIT to T4]
103
Q

Where is T3/T4 hydrolyzed from TG?

A

lysosome in follicular cell, by proteases

104
Q

What happens to leftover MIT and DIT on TG?

A
  • deiodinized in follicular cell by deiodinase
105
Q

What is effect of thyroid deiodinase?

A

have I deficiency since you can’t recycle it

106
Q

What is mechanical reason for more T4 than T3?

A

peroxidase rxn of combining two DIT is faster than one DIT and one MIT

107
Q

What is Wolff-Chalkoff effect?

A
  • high level of I in thryoid inhibits organification [formation MIT/DIT] and synthesis of thyroid hormones
  • inhibits thyroid peroxidase
108
Q

What can you use to take a thyroid scan?

A

radioactive iodine [in small dose]

109
Q

What 2 things can radioactive iodine in large dose treat?

A
  • treat hyperthyroidism to destroy thyroid tissue

- treat thyroid cancer in really large doses

110
Q

What can large does of non-radioactive iodine treat?

A
  • can treat hyperthyroidism

- because of Wolk-chalkoff effect, large I blocks more thyroid hormone production

111
Q

What is mech for escape from wolk-chaikoff effect?

A

escapes after 10 days
over space of a week all that iodine actually downregulates the transporter so less I comes in so thyroid is able to recover

112
Q

How does T4 normally circulate?

A

bound to thyroid binding globulin [TBG]

99% bound

113
Q

What happens if you don’t have TBG?

A

lower T4 but might still be normal

114
Q

Where does majority of T3 comes from?

A

75% from conversion from T4 in liver, heart, muscle, fat, CNS, pituitary
25% directly from thryoid

115
Q

What type of deiodinase to downregulate T3?

A

type 3 deiodinase

116
Q

What type of deiodinase to upregulate T3?

A

Type 1 and Type 2

117
Q

Does thyroid hormone bind outside or inside cell?

A

inside cell

118
Q

Where does T4-> T3 conversion happen [extra or intracellular]?

A

intracellular

119
Q

What are effects of thyroid hormone

A

growth: growth formation, bone maturation
CNS: maturation of CNS
BMR: more Na-K atpase, more O2 consumption, more heat production, increased BMR
metabolism: more glucose absorption, more glycogenolysis, more gluconeogensis, more lypolysis, more protein synthesis and degradation [net catabolic]
CV: more CO

120
Q

What happens to growth without thryoid hormone?

A

no growth

121
Q

What happens to brain development and function without thyroid hormone?

A

no brain development and function

122
Q

What is effect of thyroid hormone on heart

A
  • increases BMR
  • increases CO
  • increases thermogenesis so radiating heat out
  • can lower BP because vasodilation to radiate heat out
  • increases HR
  • increases contractility
123
Q

Without thyroid hormone are you more likely to be hypoglycemic or hyperglycemic?

A

hypoglycemic

124
Q

What does thyroid hormone do to cholesterol?

A

“helps you get rid of bad cholesterol and hold onto good cholesterol”

  • increases ApoA1 [protein on HDL]
  • increases good HDL levels
  • increases binding of LDL to LDL receptor in liver
  • increases path of LDL/cholesterol breakdown to bile acid in liver
125
Q

Effects of T3 on kidney

A
  • increases renal blood flow
  • increases Na reabsorptin
  • increasees RAAS
  • increases GFR