Flashcards in The Adrenal Gland Deck (107):
1
What is the adrenal gland?
a hybrid gland consisting of a cortex and a medulla
2
What is important about the hormones of the adrenal gland?
regulators of metabolism and adaptation to stress
3
What is cortisol?
glucocorticoid which increases plasma glucose levels
4
What is aldosterone?
mineralocorticoid promotes salt and water retention by the kidney
5
What else is secreted by the adrenal cortex?
weak androgens which can be converted to testosterone
6
What are the products of chromaffin cells?
epinephrine but also produces small amounts of norepinephrine
7
What are steroid hormones derived from?
cholesterol - different ring structures and side chains
8
What is the common features of steroid hormones?
lipid soluble so are freely permeable
9
How are steroid hormones are carried in the blood ?
complexed to binding globulins - corticosteroid binding globulin binds cortisol
10
Where are the enzymes that produce steroids from cholesterol?
in the mitochondria and smER
11
What are the sources of free cholesterol in the cell is maintained relatively constant?
cellular synthesis of cholesterol from acetate
LDL -> esterified cholesterol from LDL droplets inside the cell
12
What is the rate limiting step in steroidogenesis?
the transport of free cholesterol from the cytoplasm to the mitochodria
13
How is cholesterol carried into the mitochondria?
Steroidgenic Acute Regulatory Protein (StAR)
14
What is cholesterol converted to in the inner membrane?
pregnenolone by CYP450scc -side chain cleavage aka desmolase
15
Where does cholesterol conversion occur?
in the adrenal, ovary and testis
16
What converts pregnenolone to 17a-hydroxypregnenolone?
CYP17
17
What converts pregnenolone and pregesterone to mineralocorticoids?
CYP11B2
18
Where is CYP17 found?
not in glomerulosa
19
Where is CYP11B2 found?
only in the glomerulosa
20
What is synthesised in the fasiculata?
cortisol
21
Which enzyme esterifies free cholesterol?
acyl coA cholesterol transferase
22
Which enzyme turns lipid droplets back into cholesterol?
hormone sensitive lipase
23
What increases the activity of hormone sensitive lipase?
ACTH
24
How many reactions modify cholesterol to cortisol?
5
25
What is the first enzyme in the modification of cholesterol to cortisol and where is it located?
CYP11A1
inner mitochondrial membrane
26
How is the activity of StAR increased?
ACTH stimulates Gs -> cAMP-> PKA which phosphorylates StAR
27
How is cortisol predominantly transported in the blood?
CBG - 90%
albumin - 5-7%
28
What does the unbound form of cortisol do?
exerts its effects on tissues and feedsback on the pituitary and hypothalamus
29
What does the liver conjugate cortisol with?
gluconoride or sulfate
30
What is the circulating half life of cortisol?
70mins
31
How does cortisol act?
through glucocorticoid receptor which bind the Glucocorticoid response Element and regulates gene transcription
32
What happens to GR in the absence of cortisol?
resides in cytoplasm in complex with chaperones including heat shock protein 90 and cyclophillins
33
What happens to GR in the presence of cortisol?
moves to the nucleus and binding GRE near basal promotors of cortisol regulated genes
recruits co-activator or co-repressor proteins followed by covalent modification of chromatin
34
How is c-GR complex turned off?
phosphorylation and nuclear export or degradation of the GR
35
How is cortisol inactivated?
by 11b-HSD2
36
Why would cortisol be inactivated?
to prevent it binding and activating MR
37
What is the enzyme that activates cortisol?
11b-HSD1
38
Where is 11bHSD1 found?
in cells that express the GR including liver, adipose, skin and CNS
39
What can happen with natural black liquorice?
inactivates 11b-HSD2 which results in MR activation by cortisol, Na retention, increased BP and muscle spasms
40
What are the actions of cortisol essential for?
gluconeogenesis
suppression of inflammatory and immune responses
modulation of CNS function
vascular responsiveness to catecholamines
surviving fasting
41
What does cortisol stimulate?
protein and triglyceride catabolism
gluconeogenesis in the liver
42
What does cortisol inhibit?
glucose uptake by the body - goes to brain
elevates blood glucose - diabetogenic
bone formation
non-essential function i.e. growth
43
How is cortisol secretion regulated by the HP-axis?
CRH and ADH secretion are controlled by the supraoptichiasmatic nucleus and retina - circadian rhythm which thus regulates ACTH and cortisol
44
What happens if there is no ACTH?
fasciculata and reticularis atrophy and no cortisol production - dependent on exogenous glucocorticoids
45
What happens in excess ACTH?
enlarged adrenals, excess steroids
46
What does adrenal hyperplasia do in men and women?
women - virilism, hirsutism, clitoral hyperplasia
men - precocious puberty
47
What causes adrenal hyperplasia?
21-hydroxylase deficiency
48
What happens when the body cannot cope with the demand for cortisol?
ACTH might be used to stimulate androgen production pathway
49
What is the difference between ACTH independent and dependent Cushings Syndrom?
dependent - pituitary tumour - Cushings disease
independent - adrenal tumour
50
What are the 2 primary consequences of Cushings syndrome?
Salt and Water retention with renal loss of K - results in moon face and cardiac hypertrophy due to increased BP and peripheral oedema and glucocorticoid induced diabetes
Catabolism causes muscle wasting, fat accumulation, osteoporosis, kyphosis, buffalo hump, fracture, ulcered skin and poor wound healing§
51
What is Addisons disease?
a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hromones
52
What are the symptoms of addisons disease?
over production of ACTH
skin hyperpigmentation
53
What are the glucocorticoid deficiency symptoms?
hypglycaemia, hypotension, changes in mood, muscle weakness, anemia, decreased GI motility and appetite
54
What are the mineralocorticoid deficiency symptoms?
loss of Na, craving salt, loss of fluids and retention of K, hypotension, muscle fatigue and pain due to increased EC K+
55
What does aldosterone govern?
EC volume due to action on Na retention
56
Where is aldosterone produced?
zona glomerulosa
57
What are the two integrated systems for balancing salt and water?
ADH and aldosterone
58
What enzyme converts cholesterol to aldosterone?
aldosterone synthase
59
What limits the rate of Aldosterone secretion?
there is no storage pool of the hormone
60
What stimulates the production of aldosterone?
ACTH, EC K, and angiotensin II
61
How much aldosterone is free in the plasma?
37%
62
What is aldosterone bound to in the plasma?
GBG and albumin
63
Where does aldosterone act?
mainly kidney
colon, salivary glands, sweat
64
How does aldosterone act?
binds mineralocorticoid receptor and regulates gene transcription
65
What ensures cortisol does not activate the MR?
11b-HSD2
66
What does aldosterone stimulate transcription of?
ROMK channel
ENaC
Na-K pump
SGK-1
67
What is the function of the ROMK?
increases K secretion on apical membrane
68
What is the function of ENac?
brings Na into the cell on the apical membrane
69
What is the function of the Na-K pump?
takes Na into the blood and K into the cell on the basolateral membrane
70
What is the function of SGK-1 expression?
enhances ROMK, ENaC and Na-K pump
decreases degradation fo ENac
serine/threonine kinase
71
What can loss of aldosterone result in?
hyperkalaemia, hypotension
72
What sort of change does a 2% change in Na excretion cause?
3L change in ECV
73
How is aldosterone regulated by Na and water levels?
Feedback through the RAS system
AngII binds to AT1 receptor
Gaq -> PLC -> DAG and IP3
Ca increases depolarising cell and increasing Ca further
Ca stimulates
production of P450scc
delivery of cholesterol
aldosterone synthase
74
What does Ca stimulate in glomerulosa cells?
production of P450scc
delivery of cholesterol
aldosterone synthase
75
What other two systems increase and regulate aldosterone synthesis?
High EC K+
ACTH
76
How does BP regulate aldosterone synthesis?
low BP is detected by baroreceptors in the kidney which release renin from Juxtaglomerular cells and cause activation of sympathetic fibers and innervate JG cells through b1-adrenergic receptors
77
what prevents chromaffin cells from developing into post-ganglionic sympathetic neurons?
cortisol inhibits neuronal differentiation
78
What does cortisol induce in the chromaffin cells?
the expression of PNMT which converts norepinephrine to epinephrine
79
where are adrenal medullary catecholamines secreted?
into the blood where they act as hormones
80
What does ACTH stimulate in the adrenal medulla?
the conversion of tyrosine to DOPA
81
What enzyme converts tyrosine to DOPA?
tyrosine hydroxylase
82
What is DOPA converted to and by what?
dopamine by amino acid decarboxylase
83
How is dopamine stimulated to convert to norepinephrine?
ACTH stimulates dopamine b-hydroxylase
84
Where does norepinephrine go?
diffuses out of the granule
85
Where does epinephrine go?
back to the granule by vesicular monoamine transporters VMATS
86
What is epinephrine stored in the chromaffin granule with?
ATP, Ca, chromogranins
87
What is the difference between the needs for epinephrine and norepinephrine?
all of the epinephrine is derived from the medulla
only 30% of circulating norepinephrine is derived from the medulla
88
Where does the rest of the norepinephrine come from?
the postganglionic sympathetic nerve terminals
89
Where does the rest of the norepinephrine come from?
the postganglionic sympathetic nerve terminals
90
Where are the autonomic centres that initiate the sympathetic response?
hypothalamus and brain stem
91
Where do the hypothalamus and brain stem recieve inputs from?
the cerebral cortex, limbic system and other regions of the hypothalamus and brain stem
92
What are the general signals which stimulate secretion of epinephrine and norepinephrine?
various forms of stress, including exercise, hypoglycaemia and surgery
93
What is the chemical signal for catecholamine release?
ACh -> nAChR on the chromaffin cells
94
What enzymes does ACh increase the rate of?
tyrosine hydroxylase
dopamine b-hyrdoxylase
exocytosis of chromaffin granules
95
How does cortisol regulated catecholamine secretion?
maintaining adequate expression of PNMT
96
what are the primary enzymes involved in degrading catecholamines?
MAO - neuronal mitochondria
COMT
97
What is the fate of catecholamines in non-neuronal tissues?
methylation to metanephrine and metanorepinephrine
98
What does MAO convert metanephrine to?
VMA - vanillylmandelic acid
99
What does the liver and gut do to metanephrine?
conjugates them to sulfate or glucuronide
100
Where is epinephrine more potent than norepinephrine?
the liver where it activates b2 increaseing cAMP
101
where do catecholamines decrease cAMP?
pancreatic b cells on a2
102
Where do catecholamines increase IP3 and DAG?
a1 on vascular smooth muscle
103
Where are b1 and b3 found?
heart and adipose tissue respectively
104
What are the physiologic actions of catecholamines?
fatty acids broken down
blood glucose increased
HR and force increases
digestion slows
respiratory passages dilate
bronchiole dilation occurs
BP goes up from vasoconstriction
105
What is pheochromocytoma?
uncommon tumour caused by hyperlasia of the adrenal medulla or other chromaffin tissues
106
What does pheochromocytoma cause?
sudden hypertension
headaches
episodes of sweating
anxiousness
tremor
glucose intolerance
107