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adrenal gland Flashcards

1
Q

what is the function of aldosterone and what releases it ?

A

regulates sodium and potassium balance –> secretes potassium and reabsorb sodium

Zona glomerulosa of the cortex of the adrenal gland

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2
Q

what is the function of cortisol and what secretes it ?

A

regulates metabolism, increase blood glucose , critical for physiological stress response

Zona fasciculata of the cortex of adrenal gland

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3
Q

what is the function of androgens and where they are secreted?

A

Growth and development of both genders

zona reticularis of the cortex of the adrenal gland

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4
Q

what releases catecholamines?

A

adrenal medulla

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5
Q

which part of the adrenal gland releases which kind of hormones?

A

zona glomerulosa —> mineralocorticoids –> aldosterone

zona fasciculata —> glucocorticoids –> Cortisol

zona reticularis —> adrenal androgens —> male sex hormones mainly –> testesterone and DHEA ( gets converted to Testesterone, Estrogen )

Adrenal medulla —> catacholamines

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6
Q

what is the precursor of adrenal steroids ?

A

cholesterol

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7
Q

what are the characteristics of cholesteorl?

A

cholesterol has total of 27 carbon atoms

characterized by presence of steroid nucleus —> four conjoined rings

lipid –> found in cell membranes

amphipathic –> have both hydrophilic and hydrophobic parts

2 forms –> free form , stored after esterification

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8
Q

what are the 4 conjoined rings of cholesterol?

A

3 benzene rings

cyclopentane ring

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9
Q

what are the functions of cholesterol ?

A

part of cell membrane

precursor of steroidal hormones

precursor of vit D

precursor of bile acid and salt

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10
Q

how is cholesterol synthesized?

A

endogenous synthesis –> form acetyl coa by HMG synthase

Exogenous source : Diet

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11
Q

what is the stored form of cholesterol?

A

in cytoplasm as cholesterol esters

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12
Q

what is the effect of ACTH on cholesterol esteR?

A

stimulates its hydrolysis via esterase and it will be released for hormone synthesize

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13
Q

what is responsible for moving cholesterol from cytoplasm to mitochondria?

A

Steroidogenic acute regulatory protein ( STAR )

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14
Q

what converts cholesterol (27 carbons ) to pregnenolone ( 22 carbons ) ?

A

Cytochrome p450 side chain cleavage enzyme ( P450scc )

pregnenolone is the precursor for adrenal hormones

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15
Q

what are the requirements for the synthesize of adrenal gland hormones?

A

Cyt P450 monooxygenase for hydroxylation

Dehydrogenases

isomerase and lyases

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16
Q

what is the cofactor for cyt p450 monooxygenase?

A

NADPH

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17
Q

where does the synthesize of adrenal hormones occur?

A

mitochondria

endoplasmic reticulum

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18
Q

how does cholesterol enter the adrenal hormones synthesize pathway?

A

cholesterol —–> pregnenolone via P450CSS

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19
Q

what is the main pathway that cholesterol enter in and then it can be changed later?

A

aldosterone synthesize pathway

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20
Q

what are the first 3 steps of aldosterone pathway?

A

cholesterol ——-> pregnenolone ( P450SCC) , cholesterol is moved to the mitochondria via STAR

pregnenolone ——> progesterone

progesterone —-> deoxycorticosterone ( limiting step) —> NO COME BACK

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21
Q

what enzyme is responsible for converting pregnenolone to progesterone ?

A

3 beta hydroxysteroid dehydrogenase

3B HSD

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22
Q

what is the enzyme responsible for converting progesterone to deoxycorticosterone?

A

21 hydroxylase

RATE LIMITING STEP

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23
Q

when the pathway can be shifted to cortisol pathway?

A

at pregnenolone

at progesterone

at both molecules the pathway can be shifted to the cortisol pathway

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24
Q

what is the enzyme responsible for shifting the pathway from aldosterone to cortisol?

A

17 alpha hydroxylase

pregnenolone —–> 17-OH pregnenolone

progesterone ——> 17 - OH progesterone

THEN NOW WE ARE IN THE CORTISOL PATHWAY

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25
what is the enzyme that converts 17-OH pregnenolone to 17 OH progesterone to advance in the cortisol pathway?
3 beta hydroxysteroid dehydrogenase 3B HSD
26
what is the enzyme responsible for converting 17 OH progesterone to 11 deoxycortisol?
21 hydroxylase khalas rate limiting step no come back
27
when is the pathway can be shifted from cortisol to Androgens?
similar to the first shift at pregnenolone and progesterone 17-OH pregnenolone 17-OH progesterone
28
what is the enzyme responsible for the shift from cortisol to androgens pathway?
17,20 lyase
29
what happens when you have deficiency in 21 hydroxylase?
you can be forming aldosterone or cortisol cuz it is the one responsible for the limiting step in both pathways the pathway will be shifted towards androgens only and mainly NO MORE ALDOSTERONE OR CORTISOL
30
what signaling method does ACTH uses?
G protein second messenger pathway Adenylate cyclase
31
describe the mechanism of ACTH and it is signaling pathway?
ACTH will bind to the receptor ----> G protein gets activated ---> Adenylate cyclase is activated ---> increased CAMP ----> PKA ---> cholesterol is released from the free form and STAR is activated to transport cholesterol into the mitochondria
32
how are the adrenal gland cortex hormones transported?
they are hydrophobic and lipid soluble so they require binding proteins in the blood they bind to Albumin, globulins and other specific steroid binding protein called TRANSCORTIN
33
how do adrenal cortex hormone exert their functions on other cells ?
they are lipid soluble so they pass through the membrane directly and enter the cell
34
where are the receptors for the adrenal cortex hormones located?
intracellularly on THE CYTOPLASM
35
what is the end effect of adrenal cortex hormone binding to their receptors?
alter gene transcription
36
what is the function of cortisol ?
protein catabolism in all body except liver immune suppression due to protein catabolsim lipolysis in limbs and lipogenesis in the trunk '''' increase glucose level
37
what are the stimulus of aldosterone secretion?
renin, ang2 Hyperkalemia K+
38
what does the binding of aldosterone to its nuclear receptor leads to?
transcription of genes that lead to the formation of proteins responsible for sodium transport
39
what are the catecholamines?
dopamine norepinephrine epinephrine
40
where are the catecholamines synthesized?
Dopamine and norepinephrine ---> CNS epinephrine is minimal in CNS and is more in adrenal gland
41
what is the methylated form of norepinephrine ?
epinephrine and it is made in adrenal medulla
42
what is the signaling method for catecholamines ?
Second messenger pathway ---> CAMP ---> protein kinase A
43
what is the function of epinephrine?
glycogen degradation and increase glucose blood levels lipolysis
44
what type of hormones are catecholamines ?
Tyrosine derived
45
what is the rate limiting step of synthesize of epinephrine ?
tyrosine --------> L - DOPA L-dopa will be converted to dopamine then dopamine to norepinephrine and then finally epinephrine
46
what is the enzyme responsible for the rate limiting step?
tyrosine oxidase
47
what is the signaling cascade of epinephrine?
adrenergic receptors -----------> G protein/Adenylate kinase------> increase CAMP levels ------> Protein kinase A
48
what is the function of PKA in the heart?
phosphorylation of phospholamban ----> stimulate Ca2+ atpase resulting in greater uptake and storage of ca+ by sarcoplasmic reticulum ----> faster relaxation and briefer contraction
49
what is the function of PKA in the liver and skeletal muscles?
phosphorylation of glycogen phosphorylase -------> glycogenlysis
50
what is the result of short term stress?
Release of epinephrine and norepinephrine
51
what is the result of long term stress?
ACTH ---> release of glucocorticoids and mineralocorticoids
52
what is cushings syndrome?
hypersecretion of cortical hormones
53
what is adrenogenital syndrome ?
hypersecretion of gonadotrpins
54
what is addison disease ?
adrenal insufficiency or hypofunction primary ---> ACTH is high but no response secondary ---> low ACTH , Low adrenal hormones
55
what is conns syndrome ?
primary aldosteronism
56
what are the signs and symptoms of cushing disease ?
it is when cortisol is increase so it will also increase androgens and aldosterone leading to : adiposity : deposition of tissue in the face and neck and trunk moon shaped face buffalo hump weight gain Na and H2O retention K is lost hypokalemia hirsutism
57
what is the number one test for diagnosing cushing ?
Measure cortisol level : 24 hour test for urinary cortisol Serum cortisol salivary cortisol
58
what do you have to consider when measuring cortisol level?
Cortisol level is affected by stress and circadian rhythm Concentration of cortisol are highest in the morning and lowest at night
59
why is the 24 hour urinary cortisol test reliable?
24 hour urinary cortisol test gives reliable indication of how much cortisol is produced a day because it is covering the whole day and every point assessing the increase in morning and decrease in night IF it is higher than 50-100 this indicates cushing syndrome
60
what is the second test for diagnosing cushing syndrome ?
Overnight dexamethasone suppression test taking a dose of synthetic cortisol ( dexamethasone ) to see how it affects the cortisol hormone in the blood
61
what happens when you give low dose of dexamethasone ( 1-2 mg ) to a normal person at night?
the dexamethasone ( synthetic cortisol ) should SUPPRESS THE cortisol level by negative feedback and SUPRESS ACTH secretion level
62
when is high dose of dexamethasone 8 mg used ?
detection of ectopic ACTH --> ACTH IS SECRETED FROM OTHER PLACE THAN PITUITARY if you give high dose and cortisol is STILL HIGH and ACTH is still HIGH then it is ectopic if cortisol is still high and ACTH IS LOW = primary ---> adrenal cushing
63
what is cushing disease ?
hypercorticolism due to pituitary tumor if you give low dexamethasone and it doesnt suppress then it is cushing syndrome ( elevated cortisol level ) if you give HIGH dexamethasone and it suppresses the cortisol lvl then it is pituitary tumor ---> CUSHING DISEASE if it doesnt and ACTH IS LOW then it is primary like adrenal adenoma
64
What is the most specific test for addison disease?
ACTH stimulation test
65
describe the ACTH stimulating test?
Measures blood and urine cortisol before and after injection of ACTH ---> short/rapid ACTH test after 30-60 minutes of injection measures the cortisol level normally it should rises the cortisol if not = ADRENAL INSSUFICIENCY
66
what is congenital adrenal hyperplasia ( CAH ) ?
genetic defect that results in a missing enzyme for one of the hormones
67
what is the commonest enzyme deficiency for CAH ?
21 hydoxylase this will shift the pathway toward androgens only no cortisol no aldosterone
68
what would happen to ACTH when you dont have 21 hydroxylase?
no 21 hydroxylase = no cortisol = HIGH ACTH
69
what is pheochromocytoma ?
tumor of adrenal meddulla secondary cause of hypertension due to increased production of catecholamines
70

biochem Y2S1 (5 decks)

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