regulation of adrenocortical steroidogenesis W6 Flashcards

1
Q

cholesterol structure?

A

HO group (polar head group)
steroid body (4 rings)
hydrophobic side-chain

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2
Q

cholesterol as a component of cell membranes?

A

aligns between membrane phospholipids
attracted to polar head and hydrophobic tail

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3
Q

what are steroids soluble in

A

steroids are fat soluble

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4
Q

2 main types of steroid hormones? where are they made?

A

corticosteroids (cortex of adrenal gland)
sex steroids (made in gonads)

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5
Q

types of corticosteroids?sa

A

mineralocorticoids
glucocorticoids
adrenal androgens

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6
Q

mineralocorticoids function?

A

salt and water retention

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7
Q

glucocorticoids function

A

glucose synthesis
protein and lipid metabolism
inflammation, immune response

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8
Q

adrenal androgens function?

A

fetal steroids and growth

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9
Q

3 types of sex steroids?

A

androgens
oestrogens
progesterones

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10
Q

what is vitamin D?

A

steroid hormone

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11
Q

key adrenal steroid hormones? structural differences?

A

aldosterone (O, CH, OH)
cortisol (OH)
androstenedione (O)

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12
Q

what distinguishes a glucocorticoid from other steroids?

A

11 beta hydroxylase group (?)

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13
Q

steroid hormones mechanism of action (classic ‘genomic’)

A

circulating steroid hormones bind to hormone receptors in cytoplasm, makes active transcription complex that acts on DNA in nucleus creating mRNA that causes protein synthesis in cytoplasm

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14
Q

how long do steroid hormones take to act?

A

30 mins - 48 hrs

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15
Q

‘non-genomic’ mechanism of steroid hormones?

A

receptors such as ion channels in plasma membrane activated directly by steroid binding

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16
Q

‘non-genomic’ mechanism of steroid hormones time to act?

A

<1m

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17
Q

how are steroid hormones made from cholesterol?

A

hydrophobic 6 carbon side chain removed
varied substituent at C-17
Extra specificity from side chain modification eg C-11

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18
Q

2 types of enzymes involved in steroid synthesis?

A

cytochrome P450s (CYPs)
steroid dehydrogenases/reductases

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19
Q

where are cytochrome P450s highly expressed?

A

liver (drug detoxification)
organs that synthesize steroids (adrenal cortex, testis, ovary, placenta)

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20
Q

function of cytochrome P450s?

A

cleave or modify cholesterol side groups

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21
Q

function of steroid dehydrogenases/reductases?

A

interconvert active and inactive forms of steroid

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22
Q

cortisol inactive form?

A

cortisone

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23
Q

what steroid dehydrogenase/reductase converts cortisol to cortisone and vice versa?

A

11β-HSD1 and 11β-HSD2

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24
Q

cortisol pathways?

A

released from adrenal gland into circulation, 90%+ binds to transport protein and affects target tissues.
some cortisol recycles through liver, converted to cortisone which circulates and reaches target tissues where it is reactivated by 11β-HSD1

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25
what do the adrenal glands do!
coordinates the bodies response to internal physiology and environmental stimuli
26
where are the adrenal glands located?
around 12th thoracic vertebra positioned bilaterally and anteriorly above kidneys
27
anatomists name for adrenal glands?
suprarenal glands
28
2 endocrine axes that adrenal glands play a role in?
hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine sympathetic nervous system
29
which part of the adrenal glands is involved in the HPA axis
adrenal cortex
30
which part of the adrenal glands is involved in the neuroendocrine sympathetic nervous system
adrenal medulla
31
function of adrenal cortex?
makes steroid hormones
32
adrenal medulla function?
extension of sympathetic nervous system makes catecholamines
33
blood supply to adrenal cortex?
short arteries penetrate the capsule, supply a subcapsular plexus of arterioles capillary sinusoids extend through the cortex separating chords of cells this structure allows rapid transmission of stimuli to cells and products to targets
34
adrenal medulla blood supply?
receives long cortical arteries and capillaries from cortex
35
adrenal medulla and cortex venous drainage?
drain via central and medullary vein
36
zones of adrenal cortex?
zone glomerulosa zona fasciculata zona reticularis
37
where is aldosterone made
zona glomerulosa
38
what is aldosterone under control of
RAS (renin-angiotensin system)
39
what does aldosterone regulate
salt and water retention in kidney distal tubule
40
aldosterone is the principle what?
aldosterone is the principle mineralocorticoid in humans
41
cortisol is the principle what?
cortisol is the principle glucocorticoid in humans
42
where is cortisol made
zona fasciculata
43
what is cortisol under control of
HPA axis
44
what does cortisol regulate?
glucose homeostasis stress response inflammation immune response
45
where are C19 adrenal androgens made
zona reticularis
46
what are C19 adrenal androgens under control of
HPA axis
47
C19 adrenal androgens function?
intracrine conversion to testosterone and oestradiol in peripheral tissues prenatal and postnatal DHEA production
48
positive regulators of CRH (cortisol releasing hormone)
serotonin acetylcholine encephalin
49
negative regulators of CRH (cortisol releasing hormone)
alpha-adrenergic agonists GABA, endorphin dopamine
50
circadian rhythm of CRH release?
CRH high in early morning (4-8) and lower later in day CRH regulates ACTH release ACTH high on waking (6-10) and lowest in middle of night
51
what are corticotropes
cells in anterior pituitary that release ACTH, MSH and lipotropin
52
homeostatic feedback regulation of cortisol synthesis by the HPA axis?
circadian rhythm and stress inputs stimulate CRH release from hypothalamus CRH stimulates ACTH production from pituitary corticotrophs ACTH stimulates cortisol production from adrenal zona fasciculata cortisol feeds back on release of CRH from hypothalamus and ACTH from the anterior pituitary
53
StAR protein function?
steroid acute regulatory protein sits in membrane of mitochondria and promotes transport of cholesterol from cytoplasm into mitochondria where steroid hormones are made crucial regulatory step!!
54
what hormone levels rise as plasma glucose falls?
glucagon adrenaline noradrenaline growth hormone cortisol
55
dual action of cortisol?
anabolic in liver to promote gluconeogenesis catabolic in peripheral muscle and fat to promote protein and lipid breakdown
56
anabolic actions of cortisol?
increased gluconeogenesis and liver glucose output
57
catabolic actions of cortisol?
inhibition of glucose uptake by peripheral muscle fat and tissue immune system suppression increased muscle protein breakdown increased fat breakdown increased bone resorption increased appetite and central fat deposition
58
pathophysiological actions of cortisol - anabolic?
elevated plasma glucose - secondary diabetes mellitus
59
pathophysiological actions of cortisol - catabolic?
muscle and connective tissue wasting and weakness poor wound healing and skin ulcers uncontrolled muscle protein breakdown increased fat redistribution osteoporosis uncontrolled appetite and central fat deposition excess mineralocorticoid action = Na+ and fluid retention and hypertension
60
disease of cortisol excess?
Cushing's Disease
61
Cushing's disease - features
hypertension low plasma K+ elevated plasma cortisol low plasma aldosterone and renin activity.
62