Adrenal (synthesis and regulation)

Question 1

principle source of cholesterol for steroidogenesis is what

Answer 1

circulating low-density lipoprotein (LDL)

Question 2

how do LDLs enter steroidgenic cells

Answer 2

receptor mediated endocytosis

Question 3

what happens to cholesterol in steroidgenic cells

Answer 3

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

Question 4

what is the first step in steroid hormone synthesis

Answer 4

conversion of cholesterol to pregnenolone

Question 5

rate limiting step in biosynthesis of steroids is what?

Answer 5

transfer of cholesterol to the inner mitochondrial membrane

Question 6

what catalyzes the conversion of cholesterol to pregnenolone

Answer 6

P450scc

Question 7

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

Answer 7

steroidogenic acute regulatory (StAR) protein

Question 8

synthesis of StAR protein can be rapidly induced by what

Answer 8

a cAMP dependent mechanism

Question 9

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

Answer 9

unrestricted

Question 10

Pregnegolone is used to synthesize what

Answer 10

all adrenal, gonadal, and placental steroids

Question 11

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

Answer 11

which steroidgenic enzymes are expressed by that tissue

Question 12

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

Answer 12

steroid hormones

Question 13

congenital deficiencies in steroidgenic enzymes can lead to what

Answer 13

deficiency in steroids past the block in the pathway

build up of intermediates ahead of the block in the pathway

Question 14

when are steroid hormones released

Answer 14

as soon as they are synthesized

Question 15

how are steroid hormones released

Answer 15

diffusion through plasma membrane

Question 16

what provides a reservoir of precursor for steroid hormone synthesis

Answer 16

storage of cholesterol esters

Question 17

what mobilizes stored cholesterol for steroidgenesis

Answer 17

tropic hormones

Question 18

how do tropic hormones mobilize stores cholesterol

Answer 18

stimulate cholesterol esterase

inhibit acyltransferase activity

Question 19

how is cholesterol converted to cholesterol esters

Answer 19

cholesterol acyltransferase in the ER

Question 20

binding proteins able what for steroid hormones

Answer 20

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

Question 21

what are the steroid binding proteins (name them)

Answer 21

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

Question 22

corticosteroid-binding globulin (CBG) binds what

Answer 22

cortisol and progesterone

Question 23

sex steroid-binding globulin (SHBG) binds what

Answer 23

estrogens and androgens

Question 24

what affect plasma levels of binding proteins

Answer 24

disease
certain hormones
drugs

Question 25

fraction of steroid pool binds non-specifically to what

Answer 25

albumin

Question 26

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

Answer 26

in equilibrium with eachother

Question 27

how are steroid hormones degraded

Answer 27

conversion to inactive metabolites

Question 28

principle site of steroid inactivation is

Answer 28

liver

Question 29

after inactivation what happens to steroid metabolites

Answer 29

conjugated to glucuronic acid or sulfate

Question 30

conjugation of steroid hormone metabolites does what

Answer 30

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

Question 31

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

Answer 31

24-hour urinary excretion measurement

Question 32

in certain peripheral tissues what happens to steroid hormones

Answer 32

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

Question 33

steroid hormone receptors function as what

Answer 33

ligand-activated transcription factors

Question 34

steroid hormone receptor has what type of signal

Answer 34

nuclear localization signal

Question 35

nuclear localization signal (what does it do)

Answer 35

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

Question 36

when hormone binding site is unoccupied what do the receptors do

Answer 36

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

Question 37

what happens to chaperone proteins when steroid hormone binds its receptor

Answer 37

they dissociate

Question 38

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

Answer 38

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

Question 39

steroid receptors will only bind DNA if

Answer 39

hormone is bound to its appropriate binding site on the receptor

Question 40

hormone response element (HRE) | what is it

Answer 40

specific DNA sequences located in the promoter region of spefic genes

Question 41

typical steroid hormone receptors do what when occupied

Answer 41

form homodimers

Question 42

receptor homodimers form when?

Answer 42

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

Question 43

allow hormone-occupied receptors recognize and bind target genes

Answer 43

hormone response element (HRE)

Question 44

activation of gene transcription due to steroid hormones occurs when

Answer 44

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

Question 45

in hormone-dependent negative regulation of gene transcription what happens

Answer 45

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

Question 46

binding of receptor antagonist does what to steroid hormone receptor

Answer 46

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

Question 47

adrenal medulla (location and derivation)

Answer 47

located center of adrenal gland | derived from nuroectodermam cells

Question 48

adrenal medulla is essentially what and secretes what

Answer 48

essentially modified sympathetic ganglion | catecholamines

Question 49

adrenal cortex is derived from what

Answer 49

mesodermal cells

Question 50

what are the layers of the adrenal cortex

Answer 50

zona glomerulosa zona fasciculata zona reticularis

Question 51

all 3 zones of adrenal cortex can do what

Answer 51

synthesize pregnelone and progesterone from cholesterol

Question 52

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

Answer 52

zona glomerulosa | zona fasciculata

Question 53

DOC is converted to aldosterone where

Answer 53

zona glomerulosa

Question 54

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

Answer 54

aldosterone synthase

Question 55

the zona glomerulosa does not express what

Answer 55

17alpha-hydroxalase activity of enzyme P450c17

Question 56

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

Answer 56

neither cortisol nor androgens are formed in this zone

Question 57

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

Answer 57

minor pathway

Question 58

DOC formed in the zona fasciculata is converted into what

Answer 58

corticosterone (a glucocorticoid)

Question 59

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

Answer 59

11beta-hydroxylase

Question 60

what is the principle glucocorticoid in humans

Answer 60

cortisol

Question 61

what converts 11deoxycortisol to cortisol

Answer 61

11beta-hydroxylase

Question 62

what is required for the synthesis of cortisol and androgens

Answer 62

17alpha-hydroxylase and 17,20-lyase activities

Question 63

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

Answer 63

P450c17

Question 64

P450c17 can be found where

Answer 64

zona fasciculata | zona reticularis

Question 65

zona reticularis mainly synthesizes what

Answer 65

androgens

Question 66

what enzyme is needed for formation of cortisol and androgens

Answer 66

P450c17

Question 67

most glucocorticoids are synthesized where

Answer 67

zona fasciculata

Question 68

transcription of StAR protein is induced by what

Answer 68

ACTH | Angiotensin II

Question 69

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

Answer 69

via cAMP-dependent mechanisms | zona fasciculata and reticularis

Question 70

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

Answer 70

Ca2+-calmodulin-dependent mechanism | zona glomerulosa

Question 71

Ang-II levels are elevated when?

Answer 71

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

Question 72

what induces aldosterone synthesis

Answer 72

K+ | Ang-II

Question 73

how does K+ activate aldosterone synthesis in zona glomerulosa

Answer 73

activation of VG-Ca2+ channels

Question 74

what is the primary action of mineralocorticoids

Answer 74

maintain extracellular fluid volume by regulating Na+ resorption

Question 75

mineralocorticoids promote exertion of what

Answer 75

K+ and H+

Question 76

principle mineralocorticoids in humans

Answer 76

aldosterone

Question 77

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

Answer 77

aldosterone and DOC are in similar quantities | cortisol 100x as much as aldosterone

Question 78

what binding-globulin does aldosterone bind

Answer 78

corticosteroid-binding globulin (CSB)- weak affinity | does not have a specific aldosterone-binding globulin

Question 79

most bound aldosterone is associated with what

Answer 79

albumin

Question 80

why does cortisol not contribute to mineralocorticoid activity

Answer 80

converted to inactive cortisone in mineralocorticoid target tissues

Question 81

what converts cortisol to cortisone

Answer 81

11beta-hydroxysteroid dehydrogenase (11beta-HSD2)

Question 82

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

Answer 82

mineralocorticoid hypertension