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SF4 Exam 2 > Adrenal (synthesis and regulation) > Flashcards

Adrenal (synthesis and regulation) Flashcards

1
Q

principle source of cholesterol for steroidogenesis is what

A

circulating low-density lipoprotein (LDL)

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2
Q

how do LDLs enter steroidgenic cells

A

receptor mediated endocytosis

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3
Q

what happens to cholesterol in steroidgenic cells

A

either enters steroidgenic pathway or undergoes esterification to form cholesterol esters that coalesce into lipid droplets

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4
Q

what is the first step in steroid hormone synthesis

A

conversion of cholesterol to pregnenolone

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5
Q

rate limiting step in biosynthesis of steroids is what?

A

transfer of cholesterol to the inner mitochondrial membrane

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6
Q

what catalyzes the conversion of cholesterol to pregnenolone

A

P450scc

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7
Q

what facilitates the movement of cholesterol from outer mitochondrial membrane to the inner mitochondrial membrane

A

steroidogenic acute regulatory (StAR) protein

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8
Q

synthesis of StAR protein can be rapidly induced by what

A

a cAMP dependent mechanism

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9
Q

the flow of steroid hormone precursors form one cell compartment to the next after the formation of pregnegolone is what

A

unrestricted

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10
Q

Pregnegolone is used to synthesize what

A

all adrenal, gonadal, and placental steroids

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11
Q

specific synthetic products produced by a given steroidogenic tissue depends on what

A

which steroidgenic enzymes are expressed by that tissue

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12
Q

synthesis of what type of steroids can involve more than once cell type

A

steroid hormones

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13
Q

congenital deficiencies in steroidgenic enzymes can lead to what

A

deficiency in steroids past the block in the pathway

build up of intermediates ahead of the block in the pathway

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14
Q

when are steroid hormones released

A

as soon as they are synthesized

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15
Q

how are steroid hormones released

A

diffusion through plasma membrane

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16
Q

what provides a reservoir of precursor for steroid hormone synthesis

A

storage of cholesterol esters

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17
Q

what mobilizes stored cholesterol for steroidgenesis

A

tropic hormones

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18
Q

how do tropic hormones mobilize stores cholesterol

A

stimulate cholesterol esterase

inhibit acyltransferase activity

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19
Q

how is cholesterol converted to cholesterol esters

A

cholesterol acyltransferase in the ER

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20
Q

binding proteins able what for steroid hormones

A

higher concentrations in plasma then predicted by their limited solubility in aqueous solutions
protect from metabolization and excretion
provide plasma reservoir of steroid hormones

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21
Q

what are the steroid binding proteins (name them)

A

corticosteroid-binding globulin (CBG)
sex steroid-binding globulin (SHBG)
Vitamin D-binding globulin

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22
Q

corticosteroid-binding globulin (CBG) binds what

A

cortisol and progesterone

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23
Q

sex steroid-binding globulin (SHBG) binds what

A

estrogens and androgens

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24
Q

what affect plasma levels of binding proteins

A

disease
certain hormones
drugs

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25
Q

fraction of steroid pool binds non-specifically to what

A

albumin

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26
Q

what is the relation between free fraction of steroid hormones and that which is bound to binding proteins

A

in equilibrium with eachother

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27
Q

how are steroid hormones degraded

A

conversion to inactive metabolites

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28
Q

principle site of steroid inactivation is

A

liver

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29
Q

after inactivation what happens to steroid metabolites

A

conjugated to glucuronic acid or sulfate

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30
Q

conjugation of steroid hormone metabolites does what

A

facilitates clearance of inactive steroid hormones by:
increasing their solubility in water
decreasing affinity for binding proteins

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31
Q

what is a good clinical indicator of the function of the glands secreting the hormones

A

24-hour urinary excretion measurement

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32
Q

in certain peripheral tissues what happens to steroid hormones

A

converted to more active metabolite or a metabolite with a different action

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33
Q

steroid hormone receptors function as what

A

ligand-activated transcription factors

34
Q

steroid hormone receptor has what type of signal

A

nuclear localization signal

35
Q

nuclear localization signal (what does it do)

A

allows receptor to reside in the nucleus or be translocated to the nucleus when activated

36
Q

when hormone binding site is unoccupied what do the receptors do

A

form large molecular weight complexes with chaperones proteins (heat-shock proteins)

37
Q

what happens to chaperone proteins when steroid hormone binds its receptor

A

they dissociate

38
Q

about DNA-binding domain of steroid hormone receptors is what and what is the result of that

A

highly conservative

receptors do not bind DNA unless the hormone is bound to its appropriate binding site on the receptor

39
Q

steroid receptors will only bind DNA if

A

hormone is bound to its appropriate binding site on the receptor

40
Q

hormone response element (HRE)

what is it

A

specific DNA sequences located in the promoter region of spefic genes

41
Q

typical steroid hormone receptors do what when occupied

A

form homodimers

42
Q

receptor homodimers form when?

A

two identical hormone-bound receptors bind to a given response element

43
Q

allow hormone-occupied receptors recognize and bind target genes

A

hormone response element (HRE)

44
Q

activation of gene transcription due to steroid hormones occurs when

A

the steroid hormone bound receptor dimers recruit a complex of coactivator proteins

45
Q

in hormone-dependent negative regulation of gene transcription what happens

A

steroid hormone-bound receptor dimers recruit corepressor proteins to hormone binding site

46
Q

binding of receptor antagonist does what to steroid hormone receptor

A

induces conformational change in the receptor that may prevent coactivators from binding to it

47
Q

adrenal medulla (location and derivation)

A

located center of adrenal gland

derived from nuroectodermam cells

48
Q

adrenal medulla is essentially what and secretes what

A

essentially modified sympathetic ganglion

catecholamines

49
Q

adrenal cortex is derived from what

A

mesodermal cells

50
Q

what are the layers of the adrenal cortex

A

zona glomerulosa
zona fasciculata
zona reticularis

51
Q

all 3 zones of adrenal cortex can do what

A

synthesize pregnelone and progesterone from cholesterol

52
Q

the conversion of cholesterol to 11-deoxycorticosterone (DOC) occurs via the same pathway where

A

zona glomerulosa

zona fasciculata

53
Q

DOC is converted to aldosterone where

A

zona glomerulosa

54
Q

what does the zona glomerulusa is the only zone to express what

A

aldosterone synthase

55
Q

the zona glomerulosa does not express what

A

17alpha-hydroxalase activity of enzyme P450c17

56
Q

b/c the zone glomerulosa does not express 17alpha-hydroxylase activity of enzyme P450c17 what cannot happen

A

neither cortisol nor androgens are formed in this zone

57
Q

in the zona fasciculata formation of DOC is considered what type of pathway for this zone

A

minor pathway

58
Q

DOC formed in the zona fasciculata is converted into what

A

corticosterone (a glucocorticoid)

59
Q

what facilities the conversion of DOC to corticosterone in the zona fasciculata

A

11beta-hydroxylase

60
Q

what is the principle glucocorticoid in humans

A

cortisol

61
Q

what converts 11deoxycortisol to cortisol

A

11beta-hydroxylase

62
Q

what is required for the synthesis of cortisol and androgens

A

17alpha-hydroxylase and 17,20-lyase activities

63
Q

17alpha-hydroxylase and 17,20-lyase activities are associated with what enzyme

A

P450c17

64
Q

P450c17 can be found where

A

zona fasciculata

zona reticularis

65
Q

zona reticularis mainly synthesizes what

A

androgens

66
Q

what enzyme is needed for formation of cortisol and androgens

A

P450c17

67
Q

most glucocorticoids are synthesized where

A

zona fasciculata

68
Q

transcription of StAR protein is induced by what

A

ACTH

Angiotensin II

69
Q

transcription of StAR protein is induced by ACTH by what mechanism and where

A

via cAMP-dependent mechanisms

zona fasciculata and reticularis

70
Q

transcription of StAR protein is induced by Ang-II by what mechanism and where

A

Ca2+-calmodulin-dependent mechanism

zona glomerulosa

71
Q

Ang-II levels are elevated when?

A

renin-angiotensin system is activated by Renin due to low blood pressure

72
Q

what induces aldosterone synthesis

A

K+

Ang-II

73
Q

how does K+ activate aldosterone synthesis in zona glomerulosa

A

activation of VG-Ca2+ channels

74
Q

what is the primary action of mineralocorticoids

A

maintain extracellular fluid volume by regulating Na+ resorption

75
Q

mineralocorticoids promote exertion of what

A

K+ and H+

76
Q

principle mineralocorticoids in humans

A

aldosterone

77
Q

compare circulating levels of aldosterone, DOC, and cortisol in normal person

A

aldosterone and DOC are in similar quantities

cortisol 100x as much as aldosterone

78
Q

what binding-globulin does aldosterone bind

A

corticosteroid-binding globulin (CSB)- weak affinity

does not have a specific aldosterone-binding globulin

79
Q

most bound aldosterone is associated with what

A

albumin

80
Q

why does cortisol not contribute to mineralocorticoid activity

A

converted to inactive cortisone in mineralocorticoid target tissues

81
Q

what converts cortisol to cortisone

A

11beta-hydroxysteroid dehydrogenase (11beta-HSD2)

82
Q

if 11beta-HSD2 is deficient or inhibited what can cortisol cause

A

mineralocorticoid hypertension

SF4 Exam 2 (13 decks)

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