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Endocrinology > Regulation of adrenocortical steroidogenesis > Flashcards

Regulation of adrenocortical steroidogenesis Flashcards

(58 cards)

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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

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A

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

25
where are the adrenal glands located
12th thoracic vertebra positioned bilaterally and anteriorly on the superior poles of the kidneys
26
what are the adrenal glands a key component of
hypothalamic-pituitary-adrenal (HPA) axis (adrenal cortex) neuroendocrine sympathetic nervous system (adrenal gland)
27
what is the function of the adrenal cortex
make steroid hormones (mineralocorticoids, glucocorticoids, adrenal androgens)
28
what is the blood supply of the adrenal cortex
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
what are the zones of the cortex
zona glomerulosa (outermost) zona fasciculata (middle) zona reticularis (innermost)
30
what are the steroids synthesised in each adrenocortical zone determined by
zone-specific P450 gene expression
31
what is the function of the medulla
make catecholamines (adrenaline, noradrenaline)
32
what is the blood supply to the adrenal medulla
receives long cortical arteries and capillaries from cortex medulla and cortex drain via the central medullary nerve
33
where is the adrenal medulla located
centre of the adrenal gland
34
describe aldosterone
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
describe cortisol
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
describe adrenal androgens
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
describe prenatal DHEA production
role in maintaining an oestrogenic environment possible role in foetal development
38
describe post-natal DHEA production
possible role in initiation of puberty main source of androgens and post-menopausal oestrogen in females possible role in longevity????
39
what stimulates CRH release from the hypothalamus
circadian rhythm (daily suprachiasmatic nucleus circadian rhythm) and stress inputs (neurotransmitter-mediated stress inputs via nerve fibres in the medulla oblongata)
40
what are examples of stimulatory factors
serotonin, acetylcholine, encephalin, and ADH/ADP
41
what are examples of inhibitory factors
alpha-adrenergic agonists, GABA, endorphin, dopamine and cortisol negative feedback
42
where is CRH released from
the median eminence
43
what do plasma cortisol levels show
diurnal rhythm, diurnal CRH release regulates ACTH release from pituitary corticotrophs
44
what are the normal levels of ACTH throughout the day
high in early morning (4am-8am) lower later in the day
45
what regulates cortisol synthesis
ACTH from the zona fascicularis
46
what are the levels of cortisol throughout the day
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
what is the function of steroid acute regulatory proteins (StAR)
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
overview of cortisol
essential to survival and to resist physiological and environmental stress part of the counter-regulatory defence against hypoglycaemia
49
what is the dual action of cortisol
anabolic in the liver to promote gluconeogenesis (glucose homeostasis) catabolic in peripheral muscle and fat to promote protein and lipid breakdown
50
what is the normal action of cortisol
maintains plasma glucose levels for the brain
51
other catabolic actions of cortisol
immune system supression increased muscle protein breakdown increased fat breakdown increased bone resorption increased appetite and central fat deposition
52
pathophysiological action (anabolic)
secondary diabetes mellitus
53
pathophysiological action (catabolic)
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
what is Cushing's disease
pituitary tumour
55
what is Cushing's syndrome
adrenal or ectopic tumours
56
what is the phenotype of cushing's
hypertension, low plasma K+, elevated plasma cortisol, low plasma aldosterone and renin activity
57
what is hypertension in cushing's caused by
multiple effects of elevated plasma cortisol
58
what is the difference between an ACTH-secreting tumour and a cortisol-secreting tumour
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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