Adrenal Gland Flashcards
1
Q
what are the two sections making up the adrenal gland
A
adrenal cortex (90%) and inner medulla (10%)
2
Q
what are the 3 zones making up the adrenal cortex
A
zona glomerulosa
zona fasciculata
zona reticulosa
3
Q
which hormone is produced by the zona glomerulosa
A
aldosterone
4
Q
which hormone is produced by the zona fasiculata
A
cortisol and corticosterone
5
Q
which hormones are produced by the zona reticulosa
A
sex steroids - androgens mainly which are precursors for testosterone
6
Q
which hormone are produced by the medulla
A
catecholamines (epinephrine and norepinephrine)
7
Q
humans produce less corticosterone than poultry, but they are produced as intermediates fro synthesis of ______
A
aldosterone
8
Q
what is the main glucocorticoid produced by large mammals
A
cortisol
9
Q
what is the main glucocorticoid produced by rodents and birds
A
corticosterone
10
Q
what type of cells make up the medulla
A
modified neurons
11
Q
what is the first step of steroidogenesis common to all steroids
A
the formation of pregnenolone from cholesterol
12
Q
what is a rate limiting step of steroidogenesis
A
uptake of cholesterol regulated by StAR
13
Q
which enzyme regulate uptake of cholesterol
A
StAR protein [steroid acute regulatory protein]
14
Q
what stimulates the production of StAR
A
tropic hormones such as ACTH in the adrenal gland and gonadotropics in gonads will bind to GPCR and induce StAR gene through cAMP
15
Q
where does steroidogenesis occur
A
in the mitochondria
16
Q
what is the action of P450scc and which gene encodes this enzyme?
A
P450scc is encoded by CYP11A1 and cleaves the side chan of cholesterol to produce prgnenolone
17
Q
which enzyme converts pregnenolone to progesterone
A
HSD3B2
18
Q
which enzyme converts 11-deoxycorticosterone -> corticosterone -> 18OH-corticosterone -> Aldosterone
A
CYP11B2
19
Q
which enzyme converts pregnenolone to 17OH-pregnenolone
A
CYP17A1
20
Q
which enzyme converts 17OH-pregnenolone to 17OH-progesterone
A
HSD3B2
21
Q
which enzymes convert cortisol to cortisone and vice versa
A
HSD11B2
HSD11B1
22
Q
which enzymes do the cells found in zona glomerulosa require to produce aldosterone
A
CYP11A1 HSD3B2 CYP21A2 CYP11B1 CYP11B2
23
Q
which enzymes do the cells found in zona reticularis require to produce testosterone
A
CYP11A1
CYP17A1
HSD3B2
HSD17B
24
Q
which enzymes do the cells found in zona fasciculata require to produce cortisol/cortisone
A
CYP11A1 CYP17A1 HSD3B2 CYP21A2 CYP11B1 HSD11B2 and HSD11B1
25
tissues that produce steroids are ______ because producing steroids is _____
metabolically active
| energetic demanding
26
what is the main source of cholesterol used for steroidogensis
circulatory LDL
27
cortisol can be covered to inactive ____ by the ____ and other target cells
cortisone
| liver
28
what is the pathways of cortisol secretion
diurnal rhythm and stressors (hypoglycemia, hypotension, fever, trauma) will stimulate the hypothalamus which will release CRH which acts on the pituitary
Pituitary will release ACTH which acts on cells found in zona fasciculata in adrenals -> cortisol secretion
29
what is the feedback regulation of cortisol
negative feedback on hypothalamus and pituitary
30
what are the effects of cortisol on metabolism
increases: GLUCONEOGENESIS in liver , glycogenolysis, proteolysis, lipolysis [glucocorticoid involved in glucose metabolism and energy]
31
what are the effects of cortisol on cardiovascular system
increases myocardial contractility, cardiac output, catecholamine pressor effect
32
cortisone cannot be converted back to cortisol. true or false
false, cortisone can be converted to active form cortisol through HSD11B1
33
how is cortisol production activated
ACTH activates cortisol production from cholesterol via G-protein/cAMP signaling pathway and through enzymatic cascade
34
secretion of cortisol is ____
pulsatile
35
what is a diurnal rhythm
when the concentration of plasma hormones is highest in the morning
36
why is there a higher level of cortisol early in the morning?
the average level increases due to the summation of more frequency pulses of ACTH
37
how is circulating cortisol transported
transported by corticosteroid binding globulin CBG=transcortin or albumin
38
___ cortisol is protected from inactivation by the ____
bound cortisol
| liver
39
which enzyme converts cortisol to cortisone
HSD11B2
40
why is it important to be able to convert cortisol into its inactive form cortisone
cortisol levels are much higher than aldosterone concentrations. This high concentration of cortisol can cause it to bind to mineralocorticoid receptors NR3C2 which can cause aldosterone-like symptoms such as hypertension, hypokalemia, low renin, and low aldosterone levels . Therefore aldosterone responsive cells have to be able to inactive cortisol to be able to respond specifically to aldosterone
41
which receptors is the glucocorticoid receptor
NR3C1
42
which glucocorticoid receptor isoform has a negative feedback on the other isoform
GR beta inhibits GR alpha
43
the metabolic effect of cortisol are generally opposite to ____ and similar to ____
opposite to insulin but similar to GH
44
in muscle cells, adipocytes and lymphocytes, cortisol has a ____ effect and in liver it has a ____ effect
catabolic
| anabolic in liver
45
the overall effect of cortisol on liver is ____. how so?
anabolic: increased enzyme activity, gluconeogenesis, glycogen synthesis, glycogen storage
46
cortisol increases ____ despite the increase in ____
increases blood glucose despite the increase in glycogen storage
47
how does cortisol have an anti-inflammatory property
cortisol inhibits the immune response by decreasing the number of lymphocytes and antibody production -> anti-inflammatory
48
mechanism of action of hydrocortisone cream
used as topical anti-inflammmatory treatment because skin has HSDB1 which activates cortisone into cortisol
49
what are the 3 mechanisms used by glucocorticoid receptors to inhibit inflmmation
1. with coactivators C-fos/C-jun activated inhibitor I-kappa-B) of the immune response transcription factor NFkB
2. GR-cortisol binds and inhibits nuclear migration of NFkB
3. GR competes with NFkB for other interacting transcription factors (eg. CREB)
50
what is the main transcription factor of pathay o inflammation
NFkB
51
what are the main effects of cortisol
anti-inflammatory and glucose metabolism
52
what is Cushing's syndrome and what causes it
overproduction of cortisol due to:
- CRH producing tumor
- ACTH producing tumor
- lack of feedback control of cortisol
- cortisol producing adrenal tumor
- iatrogenic [most common cause, resulting from chronic glucocorticoid therapy]
53
what are the symptoms of Cushing's syndrome
- diabetes (increased gluconeogeneiss)
- muscle wasting (protein catabolism)
- increased and redistribution of adipose tissue
- susceptibility to infection (decreased immune cells/reponse)
- sodium retention and hypertension -> apparent mineralocorticoid excess AME
- low ACTH in primary hypercortisolism
54
what is Addison disease
adrenal hypofunction, most commonly due to destruction of the adrenal gland by an autoimmune response
55
if the adrenal glands are not functioning, what are the consequences
- very low or absence of cortisol
| - very low of absence of aldosterone
56
what is the main function of zona glomerulosa
produces aldosterone: recovery of sodium in the kidney and enhances potassium secretion into the urine adjusting extra-cellular fluid and blood volume
- regulation of fluid volume
- water absorption
- sodium/potassium homeostasis
- sodium transport
57
what structure present in the arterioles regulate how much blood goes into the capillaries
precapillary sphincters
58
the _________ is a major determinant of the BP in the arteries and controls the distribution of the blood supply to tissues
diameter of arterioles
59
which factors positively regulate the sodium appetite
- aldosterone
| - angiotensin 2
60
which factors negatively regulate the sodium appetite
increased sodium concentration of blood plasma, post-ingestive signals from the gut sensed via the vagus nerve, circulating and CNS peptide hormones/neuromodulators
61
thirst and sodium appetite effectively adjust BP and blood volume. true or false
false, thrust is much more robust in terms of effectively adjusting BP and blood volume than sodium appetite
62
_____ cells detect sodium levels in kidney tubule
macula densa cells
63
______ cells near afferent arterioles detect BP
juxtaglomerular cells
64
Pericytes near afferent arterioles produce ____
renin
65
Renin synthesis and secretion is simulated by _____ and ____
macula dense cells and juxtaglomerular cells
66
explain the renin-angiotensin-aldosterone system
- renin from afferent arterioles in kidney converts angiotensinogen from liver to angiotensin 1
- angiotensin converting enzyme from endothelial cells of lungs converts angiotensin 1 to a angiotensin 2
- angiotensin 2 stimulates aldosterone secretion by zona glomerulosa
- angiotensin 2 increases sodium absorption and potassium excretion and water retention
67
angiotensin 2 is inactivated to angiotensin 3 by _____
aminopeptidase A
68
the posterior pituitary releases ____ which also stimulates water resorption in kidney
AVP/ADH antidiuretic hormone
69
aldosterone adds ____ on distal tubule side of kidney to achieve water absorption
aquaporins
70
aldosterone activates ____ on distal tubule side of kidney to excrete potassium
ROMK and BK channels
71
aldosterone activates ____ on distal tubule side of kidney to absorb sodium
ENaC
72
aldosterone acts mainly on ____ and ____ for sodium retention and potassium excretion
distal tubules and collecting ducts of the kidney
73
what is the net effect of aldosterone
rise in plasma volume and hence blood pressure
74
what is Conn's disease
hyperaldosteronism due to hypersecretion of aldosterone usually caused by adrenal hyperplasia or tumor
75
what are the consequences of hyperaldosteronism
- excess excretion of potassium and H+ [serum alkalosis and neuropathy - hypokalemia]
- increased water retention
- increased sodium reabsorption
- increased blood pressure
76
what causes hypoaldosteronism and what are the symptoms
impaired function of aldosterone or deficiency of aldosterone production
- low sodium (hyponatremia)
- too much potassium (hyperkalemia)
- metabolic acidosis
- low BP
77
what is the function natriuretic peptides
ANP and BNP peptides that increase the excretion of water and sodium thereby decreasing blood volume and blood pressure
78
which cells produce natriuretic peptides
heart muscle cells
79
where are the natriuretic peptide receptors located
located in the glomeruli, medullary collecting ducts of the kidney, zona glomerulosa fo the adrenal cortex and in peripheral arterioles
80
mode of action of natriuretic peptides
they can inhibit renin production in kidney which will reduce angiotensin and aldosterone production + increase GFR causing excretion of sodium [natriuresis] => decreased blood volume and decrease BP
81
androgens are precursors for _____
testosterone
82
sex steroids are mainly synthesized in the ____ and regulated by
gonads regulated by gonadotropins
83
which are the female sex steroids
estrogen and progesterone
84
which is the male sex steroid
androgen
85
the zona reticularis contributes to the production of ____ and _____ regulated by _____ and _____
DHEAS and androstenedione regulate by ACTH and hypothalamic CrH
86
while aldosterone production by glomerulosa is less under the influence of _____ and more under the influence of _____, zona fasciculata and reticularis are mainly regulated by _____ and ____
ACTH
angiotensin
CRH and ACTH
87
what is CAH and what causes it
congenital adrenal hyperplasia which is caused by deficiency of CYP21A2 in zona glomerulosa and fasciculata causing reduced aldosterone and cortisol but excessive androgen production in zona reticularis causing masculinization of genitalia
88
which cells make up the adrenal medulla
Chromaffin cells
89
what are chromatin cells
modified postganglionic sympathetic neurons
90
how do chromaffin cells release catecholamines
preganglionic neurons release acetylcholine to stimulate the chromaffin cells to release catecholamines
91
what is the role of catecholamines
they coordinate fight-or-flight response to alarm by increasing blood pressure and cardiac output and dilating pupils
92
catecholamines are synthesized from ____
tyrosine
93
what is the rate limiting step of catecholamine synthesis
tyrosine into Dopa through tyrosine hydroxylase
94
epinephrine (catecholamine) synthesis is under the influence of ____
cortisol
95
which enzyme is stimulated by cortisol in epinephrine synthesis [norepinephrine to epinephrine]
phenylethanolamine N-methyltrasnferase PNMT
96
which are the 2 catecholamines that are released by medulla and their proportions
- 80% are epinephrine
| - 20% norepinephrine
97
how are catecholamines degraded
inactivated by monoamine oxidase MAO and COMT pathways into vanillylmandelic acid VMA which is excreted
98
the adrenal medulla secretes catecholamines and other hormones including ____
met-enkephalin and leu-enkephalin which are related to endorphins
99
function of enkephalins
block neurotransmitters like morphine
| act as an endogenous analgesic [runners overcoming pain and being euphoric]
100
the ____ nervous system activates the adrenal medulla in a fight-or-flight response releasing _____
sympathetic nervous system
| releasing norepinephrine and epinephrine
101
effect of epinephrine
- rapidly metabolizes fatty acids as the primary fuel for muscle action: increases muscle glycogenolysis, mobilizes glucose for the brain by increasing hepatic glycogenolysis and gluconeogenesis, preserves glucose for CNS by decreasing insulin release leading to reduced glucose uptake by muscle/adipose, increases cardiac output
102
effect of norepinephrine
elicits réponses of the CV system - increased blood flow and decreased insulin secretion
103
which are the adrenergic receptor and what do they bind
alpha and beta1 bind epinephrine and norepineprhine
| beta2 bind primarily epinephrine
104
____ activates beta2 receptors and dilates bronchioles - relief od asthma
salbutamol
105
which of epinephrine and norepinephrine has a greater effect on cardiac stimulation leading to greater cardiac output?
epinephrine
106
which of epinephrine and norepinephrine has a greater effect on constriction of blood vessels leading to increased peripheral resistance -> increased arterial pressure
norepinephrine
107
which of epinephrine and norepinephrine has a greater effect on increasing metabolism
epinephrine
108
what are the effects of cortisol suppression on adrenal medulla
epinephrine deficiency
