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Endocrinology > Regulation of adrenocortical steroidogenesis > Flashcards

Regulation of adrenocortical steroidogenesis Flashcards

1
Q

what does the adrenocorticotropic hormone do

A

ACTH (produced by corticotrophs in the anterior pituitary glands) regulates adrenal gland steroid hormone production

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2
Q

what is the cholesterol-building block

A

C27 (modified steroid)
made up of a polar head group, steroid body, and a hydrophobic side chain
cholesterol is attracted to both the polar head and the hydrophobic tail of membrane phospholipids

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3
Q

what is a steroid hormone

A

fat-soluble hormone
made from cholesterol
regulate the growth and function of many tissues

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4
Q

what are corticosteroids

A

steroid hormones made in cortex of adrenal gland

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5
Q

mineralocorticoids

A

hormones that maintain salt and water balance (electrolyte and fluid balance)

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6
Q

what is the function of glucocorticoids

A

glucose synthesis
protein and lipid metabolism
inflammation
immune response

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7
Q

what is the function of adrenal androgens

A

foetal steroids and growth

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8
Q

where are sex steroids made

A

gonads

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9
Q

what is the function of androgens

A

growth and function of the male reproductive system

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10
Q

what is the function of oestrogens

A

growth and function of the female reproductive system

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11
Q

what is the function of progesterones

A

female menstrual cycle
maintenance of pregnancy

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12
Q

what is the function of vitamin D

A

maintains calcium balance

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13
Q

what are the key human adrenal steroid hormones and their function

A

aldosterone - C21, mineralocorticoid, sodium potassium balance
cortisol - C21, glucocorticoid, physiological stress
androstenedione - C19, adrenal ‘androgen’, secondary sexual traits

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14
Q

what are the key gonadal/sex steroid hormones

A

progesterone - C21, progestogen, female steroid
testosterone - C19, androgen, male steroid
oestradiol - C18, oestrogen, female steroid

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15
Q

what is the classical genomic mechanism

A

classical receptors in the cytoplasm activated by steroid binding, translocate to nucleus
gene transcription and protein synthesis
slow action (>30 mins to 48hr)

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16
Q

what is an example of the classic genomic mechanism

A

aldosterone-regulated synthesis of kidney epithelial sodium channel subunits

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17
Q

what is the non-genomic mechanism

A

non-classical receptors, activated by steroid binding (eg ion channels in plasma membrane)
intra-cellular signalling pathways
rapid signalling (<1min)

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18
Q

what is an example of non-genomic mechanisms

A

aldosterone-mediated vasoconstriction of vascular smooth muscle and endothelial cells

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19
Q

how are steroid hormones made

A

cholesterol is a precursor for steroid hormones
hydrophobic 6-carbon side chain is removed (steroid hormones are more water soluble than cholesterol)
most steroid hormones have a varied substituent at C-17 (enzyme nomenclature indicates the site of action)
extra-specificity from the side-chain modification (again enzyme nomenclature indicates sight of action)

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20
Q

what is the action of cytochrome P450s

A

highly expressed in lover (drug detoxification) organs that synthesise steroids (adrenal cortex, testis, ovaries, placenta)
cleave or modify cholesterol side-groups

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21
Q

what is the method of action of steroid dehydrogenases/reductases

A

interconvert active and inactive forms of steroid
usually paired

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22
Q

describe cortisol metabolism and transport

A

bound and inactive hormones transported into the plasma, hormones reactivated in the target tissue
most cortisol converted to cortisone in the liver

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23
Q

how can you work out if a person is over/underproducing cholesterol

A

urine biochemical assay

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24
Q

what is the function of the human adrenal glands

A

coordinate the body’s response to internal physiology and environmental stimuli
first responder to physiological stress

25
Q

where are the adrenal glands located

A

12th thoracic vertebra
positioned bilaterally and anteriorly on the superior poles of the kidneys

26
Q

what are the adrenal glands a key component of

A

hypothalamic-pituitary-adrenal (HPA) axis (adrenal cortex)
neuroendocrine sympathetic nervous system (adrenal gland)

27
Q

what is the function of the adrenal cortex

A

make steroid hormones (mineralocorticoids, glucocorticoids, adrenal androgens)

28
Q

what is the blood supply of the adrenal cortex

A

receives blood from 30-50 short arteries penetrating the capsule
arteries supply a subcapsular plexus of arterioles
capillary sinusoids extend through the cortex separating chords of cells
allows for rapid transmission of stimuli to cells and products to targets

29
Q

what are the zones of the cortex

A

zona glomerulosa (outermost)
zona fasciculata (middle)
zona reticularis (innermost)

30
Q

what are the steroids synthesised in each adrenocortical zone determined by

A

zone-specific P450 gene expression

31
Q

what is the function of the medulla

A

make catecholamines (adrenaline, noradrenaline)

32
Q

what is the blood supply to the adrenal medulla

A

receives long cortical arteries and capillaries from cortex
medulla and cortex drain via the central medullary nerve

33
Q

where is the adrenal medulla located

A

centre of the adrenal gland

34
Q

describe aldosterone

A

principle mineralocorticoid
made in the zona glomerulosa
under the control of the reticular activating system (regulated by angiotensin II and plasma potassium)
regulates salt and water retention in kidney distal tubule

35
Q

describe cortisol

A

principle glucocorticoid
made in the zona fasciculata
under the control of the HPA axis (regulated by ACTH from pituitary gland)
regulates glucose homeostasis, stress response, inflammation and immune response

36
Q

describe adrenal androgens

A

made in the zona reticularis
under the control of the HPA axis ( regulated by ACTH from pituitary gland)
intracrine conversion to testosterone and oestradiol in peripheral tissues

37
Q

describe prenatal DHEA production

A

role in maintaining an oestrogenic environment
possible role in foetal development

38
Q

describe post-natal DHEA production

A

possible role in initiation of puberty
main source of androgens and post-menopausal oestrogen in females
possible role in longevity????

39
Q

what stimulates CRH release from the hypothalamus

A

circadian rhythm (daily suprachiasmatic nucleus circadian rhythm) and stress inputs (neurotransmitter-mediated stress inputs via nerve fibres in the medulla oblongata)

40
Q

what are examples of stimulatory factors

A

serotonin, acetylcholine, encephalin, and ADH/ADP

41
Q

what are examples of inhibitory factors

A

alpha-adrenergic agonists, GABA, endorphin, dopamine and cortisol negative feedback

42
Q

where is CRH released from

A

the median eminence

43
Q

what do plasma cortisol levels show

A

diurnal rhythm, diurnal CRH release regulates ACTH release from pituitary corticotrophs

44
Q

what are the normal levels of ACTH throughout the day

A

high in early morning (4am-8am)
lower later in the day

45
Q

what regulates cortisol synthesis

A

ACTH
from the zona fascicularis

46
Q

what are the levels of cortisol throughout the day

A

high on waking (8am-10am)
lower later in the day
activity spikes with stress
lowest in the middle of the night
cortisol rhythm is lost in disease states

47
Q

what is the function of steroid acute regulatory proteins (StAR)

A

chaperones cholesterol across the mitochondrial membrane
activity rapidly increases in response to angiotensin II to ACTH stimulation
this is the rate-limiting step in the production of steroid hormones

48
Q

overview of cortisol

A

essential to survival and to resist physiological and environmental stress
part of the counter-regulatory defence against hypoglycaemia

49
Q

what is the dual action of cortisol

A

anabolic in the liver to promote gluconeogenesis (glucose homeostasis)
catabolic in peripheral muscle and fat to promote protein and lipid breakdown

50
Q

what is the normal action of cortisol

A

maintains plasma glucose levels for the brain

51
Q

other catabolic actions of cortisol

A

immune system supression
increased muscle protein breakdown
increased fat breakdown
increased bone resorption
increased appetite and central fat deposition

52
Q

pathophysiological action (anabolic)

A

secondary diabetes mellitus

53
Q

pathophysiological action (catabolic)

A

muscle and connective tissue wasting
weakness
poor wound healing and skin ulcers
uncontrolled muscle protein breakdown
increased fat redistribution
osteoporosis
uncontrolled appetite central fat deposition
excess mineralocorticoid action (Na+ and fluid retention, hypertension)

54
Q

what is Cushing’s disease

A

pituitary tumour

55
Q

what is Cushing’s syndrome

A

adrenal or ectopic tumours

56
Q

what is the phenotype of cushing’s

A

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

57
Q

what is hypertension in cushing’s caused by

A

multiple effects of elevated plasma cortisol

58
Q

what is the difference between an ACTH-secreting tumour and a cortisol-secreting tumour

A

high plasma ACTH and high plasma cortisol in an ACTH-secreting tumour
low plasma ACTH but high plasma cortisol in a plasma-secreting tumour

Endocrinology (16 decks)

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