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command & control Y2 > regulation of adrenocortical steroidogenesis W6 > Flashcards

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
Q

what do the adrenal glands do!

A

coordinates the bodies response to internal physiology and environmental stimuli

26
Q

where are the adrenal glands located?

A

around 12th thoracic vertebra
positioned bilaterally and anteriorly above kidneys

27
Q

anatomists name for adrenal glands?

A

suprarenal glands

28
Q

2 endocrine axes that adrenal glands play a role in?

A

hypothalamic-pituitary-adrenal (HPA) axis

neuroendocrine sympathetic nervous system

29
Q

which part of the adrenal glands is involved in the HPA axis

A

adrenal cortex

30
Q

which part of the adrenal glands is involved in the neuroendocrine sympathetic nervous system

A

adrenal medulla

31
Q

function of adrenal cortex?

A

makes steroid hormones

32
Q

adrenal medulla function?

A

extension of sympathetic nervous system
makes catecholamines

33
Q

blood supply to adrenal cortex?

A

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
Q

adrenal medulla blood supply?

A

receives long cortical arteries and capillaries from cortex

35
Q

adrenal medulla and cortex venous drainage?

A

drain via central and medullary vein

36
Q

zones of adrenal cortex?

A

zone glomerulosa
zona fasciculata
zona reticularis

37
Q

where is aldosterone made

A

zona glomerulosa

38
Q

what is aldosterone under control of

A

RAS (renin-angiotensin system)

39
Q

what does aldosterone regulate

A

salt and water retention in kidney distal tubule

40
Q

aldosterone is the principle what?

A

aldosterone is the principle mineralocorticoid in humans

41
Q

cortisol is the principle what?

A

cortisol is the principle glucocorticoid in humans

42
Q

where is cortisol made

A

zona fasciculata

43
Q

what is cortisol under control of

A

HPA axis

44
Q

what does cortisol regulate?

A

glucose homeostasis
stress response
inflammation
immune response

45
Q

where are C19 adrenal androgens made

A

zona reticularis

46
Q

what are C19 adrenal androgens under control of

A

HPA axis

47
Q

C19 adrenal androgens function?

A

intracrine conversion to testosterone and oestradiol in peripheral tissues
prenatal and postnatal DHEA production

48
Q

positive regulators of CRH (cortisol releasing hormone)

A

serotonin
acetylcholine
encephalin

49
Q

negative regulators of CRH (cortisol releasing hormone)

A

alpha-adrenergic agonists
GABA, endorphin
dopamine

50
Q

circadian rhythm of CRH release?

A

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
Q

what are corticotropes

A

cells in anterior pituitary that release ACTH, MSH and lipotropin

52
Q

homeostatic feedback regulation of cortisol synthesis by the HPA axis?

A

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
Q

StAR protein function?

A

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
Q

what hormone levels rise as plasma glucose falls?

A

glucagon
adrenaline
noradrenaline
growth hormone
cortisol

55
Q

dual action of cortisol?

A

anabolic in liver to promote gluconeogenesis
catabolic in peripheral muscle and fat to promote protein and lipid breakdown

56
Q

anabolic actions of cortisol?

A

increased gluconeogenesis and liver glucose output

57
Q

catabolic actions of cortisol?

A

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
Q

pathophysiological actions of cortisol - anabolic?

A

elevated plasma glucose - secondary diabetes mellitus

59
Q

pathophysiological actions of cortisol - catabolic?

A

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
Q

disease of cortisol excess?

A

Cushing’s Disease

61
Q

Cushing’s disease - features

A

hypertension
low plasma K+
elevated plasma cortisol
low plasma aldosterone and renin activity.

62
Q
A

command & control Y2 (61 decks)

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