Arterial blood supply to kidneys?
superior, middle, inferior suprarenal
Which vein returns blood from kidney?
suprerenal v.
The sinusoid system of blood flow in the kidney allows what to be modulated?
enzymatic activity in medulla
Which zone of adrenal gland?
aldosterone synth
zona glomerulosa
Which zone of adrenal gland?
cortisol synth
zona fasciculata
Which zone of adrenal gland?
DHEA synth
zona reticularis
Which zone of adrenal gland?
catecholamine synth
medulla
The order of zonate structures in the adrenal from superficial to deep…
ZG
ZF
ZR
Synthesis of these two hormones is under pituitary ACTH control…
Cortisol and androgens
Synthesis of this hormone is under pituitary ACTH and RAAS control
aldo
Synthesis of medullae are under control of…
SNS
What is the basis of steroid synthesis throughout the layers of the adrenal gland?
absence or presence of enzymes
1st step of steroid hormone biosynthesis… catalyzed by…
cholesterol to pregnenolone
via cholesterol desmolase
What is the rate limiting step of steroid hormone synthesis?
cholesterol to pregnenolone
Cholesterol desmolase is dependent on the action of which protein, and what hormone?
StaR transport to inner mito
ACTH stimulation
Thee methods of cholesterol liberation…
LDL
hydrolysis of cholesterol esters
de novo by ACoA
Progression from cholesterol to aldosterone…
Cholesterol
to
pregnenolone
to
progesterone
to
11-deoxycorticosterone
to
corticosterone
to
aldosterone
Enzyme for…
pregnenolone to progesterone
3B-HSD
Enzyme for…
progesterone to 11-deoxycorticosterone
21B-Hydroxylase
Enzyme for…
11-deoxycorticosterone to corticosterone
11B-Hydroxylase
Enzyme for…
Corticosterone to aldosterone
aldosterone synthase (+ ATII)
The zona glomerulosa lacks which enzyme, ensuring pregnenolone can only be converted to progesterone…
17-a-hydroxylase
What substances stimulate aldosterone secretion, and rank them in order…
ANG II > Increase K > ACTH
Aldosterone binds to ______ which can then bind to ______ to stimulate sodium reabsorption, potasium/H+ secretion
binds to MR1
MR1 binds to MRE
A patient presents with…
Increased Na reabsorption: hypernatremia, fluid retention and hypertension Increased K + secretion: hypokalemia Increased H secretion: metabolic alkalosis Low renin levels
Conn’s syndrome
Deficiency in 17-a-hydroxylase leads to…
increased 11-deoxycorticosterone and corticosterone
no androgens, GC
Why is aldosterone level low in 17-a-hydroxylase deficiency?
corticosterone excess leads to HTN
Three signs of 17-a-hydroxylase deficiency…
HTN, hypokalemia, metabolic alkalosis
The Z. fasciculata converts cholesterol to…
cortisol and corticosterone
Which enzyme?
pregnenolone to 17-hydroxypregnenolone
17-a-hydroxylase
which enzyme?
progesterone to 17-hydroxyprogesterone
17-a-hydroxylase
which enzyme?
17-hydroxypregnenolone to
17-hydroxyprogesterone
3B-HSD
Z. Reticularis has which enzymes? (4)
Cholesterol desmolase
3B-HSD (vertical)
17-a-hydroxylase (horizontal)
17,20-lyase (horizontal )
Z. Fasciculata has which enzymes? (5)
Cholesterol desmolase
17-a-hydroxylase (horizontal)
3B-HSD (vertical)
21B-hydroxylase (vertical)
11B-hydroxylase (Vertical)
which 2 enzymes does Z. Fasciculata lack? meaning what can’t be produced?
aldo. synthase: no aldo
17,20-lyase: no androgens
In cortisol synthesis, 17-hydroxypregnenolone is converted to…
17-hydroxyprogesterone (3B-HSD)
In cortisol synth, 17-hydroxyprogesterone is converted to…
11-deoxycortisol (21B-hydroxylase)
in cortisol synth, 11-deoxycortisol is converted to…
cortisol (11B-hydroxylase)
Rows of Enzymes in Adrenal Hormone Synthesis (5 rows)
Row 1: desmolase
Row 2: 3B-HSD
Row 3: 21B-hydroxylase
Row 4: 11B-hydroxylase
Row 5: aldo synthase
Columns of Enzymes in adrenal hormone synthesis (2 columns)
Column 1: 17-a-hydroxylase
Column 2: 17,20-lyase
In androgen synthesis, cholesterol is converted to…
dehydroepiandrosterone (DHEA)
androstenedione
In androgen synthesis, 17-hydroxypregnenolone is converted to…
DHEA (17,20-lyase)
in androgen synthesis, 17-hydroxyprogesterone is converted
androstendione (17,20-lyase)
Cortisol has what effect on CRH?
direct inhibition
inhibits CRH on corticotrophs
ACTH release is…
circadian and pulsitile
CORT secretion occurs ____ and drops ____
high in morning, drops throughout day
In times of stress, ACTH secretion is enhanced by…
increased amplitude, not frequency
Describe the actions of cortisol on glucose…
decreased glucose utilization in fat and liver
decreased insulin sensitivity
Cortisol has what effect on protein catabolism and lipolysis?
increased
Cortisol effect on bone…
inhibit bone formation
anti-inflammatory/immune effects of cortisol
inhibits IL-2
inhibits lipocortin, decreased PGs and LTs
In the CV system, cortisol up-regulates what receptor?
alpha-1
In addition to the GR receptor, cortisol can bind ___ because it is closely related to aldosterone…
MR receptor
11B-HSD Type II has what effect on cortisol?
cortisol to cortisone: inactivation
What are three factors that enhance specificity of MR to aldosterone instead of cortisol?
cortisol binding to albumin, CBG
11B-HSD Type II
Slow aldo dissociation from MR
11B-HSD Type I does what?
cortisone to cortisol: activation
Where is 11B-HSD Type I expressed? What effect does this have on insulin?
adipose tissue, can lead to insulin resistance
Which condition?
Decreased cortisol, aldo, androgens
hyperpigmentation on elbows, knees, nipples, scars
Addison’s, Primary adrenocortical insufficiency
What three are compounds are responsible for the skin pigmentation in addison’s?
y-MSH, a-MSH, B-MSH via increased POMC/ACTH
Which condition:
low ACTH
normal aldo
no hyperpigmentation
secondary/tertiary adrenal cortical insufficiency
Cushing syndrome is caused by _____ while disease is caused by _____
syndrome: adrenal hyperplasia
Disease: excess ACTH
Cushings, ACTH is ___ while cortisol is___
low ACTH, high cortisol
Which condition?
masculinization: penis-like clitoris, scrotum-like labia
sodium loss, hypoglycemia
no GC or MC
21B-hydroxylase deficiency
Why are ACTH levels high in 21B-hydroxylase deficiency?
no cortisol neg feedback on ACTH
Synthesis of catecholamines occurs in what cell type?
chromaffin cells of medulla
What is the pathway of compounds for catecholamine synth?
tyrosine
to
DOPA
to
DA
to
NE
to
Epi
Which step of catecholamine synthesis occurs in granules?
DA to NE
Epi is produced in cytosol and stored…
in granules
Rate limiting step of catecholamine synthesis?
Tyr to DOPA (via tyrosine hydroxylase)
Enzyme for DOPA to DA
amino acid decarboxylase
enzyme for DA to NE
dopamine-B-hydroxylase
Enzyme for NE to Epi
phyneylethanolamine-N-methyltransferase
Acute stimulation has what effect on tyrosine hydroxylase?
increased activity
chronic stimulation of tyrosine hydroxylase has what effect…
increased expression and concentration
What role does cortisol play in catecholamine synthesis?
activates phenylethanolamine-N-methyltransferase
What degrades NE? where?
MAO, neuronal cytopalsm
What degrades Epi?
COMT, heart/liver/kidney
MAO and COMT convert catecholamines to…
MHPG
MHPG is converted to ____ which can be excreted in the urine.
VMA
____ is an index of SNS activity/pathology
VMA