Where are the adrenal glands located?
in the retroperitoneal cavity above each kidney. These glands receive the most blood flow per unit weight of any organ
Where does the adrenal medulla derive from?
Where does the adrenal cortex derive from?
When does the adrenal cortex differentiate in gestation?
week 8. However, this is a fetal adrenal cortex and soon after birth it involutes, and is replaced by the three-layered adult adrenal cortex
What hormones does the adrenal cortex secrete?
glucocorticoids, mineralcorticoids, and androgens
What hormones do the zone reticularis and fasciculata secrete? zona glomerulosa?
glucocorticoids (cortisol and corticosterone) and adrenal androgens (DHEA, and DHEA sulfate). NOTE: the zone reticularis develops postnatally (by 3 yo)
The zona glomerulosa secretes mineralcorticoids (aldosterone) and has abundant smooth ER
What is the blood supply to the adrenal gland?
Each gland is supplied by the superior, middle and inferior suprarenal arteries, which arise from the inferior phrenic artery, abdominal aorta and renal artery respectively. The blood reaches the outer surface of the gland before entering and supplying each layer. When the blood reaches the adrenal's center, it flows into the medullary vein. The medullary veins emerge from the hilum of each gland before forming the suprarenal veins, which join the inferior vena cava on the right side and the left renal vein on the left.
Describe the portal system of the adrenal glands
Blood enters the cortex via the capsular artery and enters a capillary system in the Z.G., which drains to the corticol sinusoid in the Z.F., the venous capillary plexus in the Z.R. while a concurrently corticol arteriolr branches from the capsular artery and drains to the medullary arteriole. The medullary arteriole then joins the venous capillary plexus near the medulla and drains to the medullary vein
How are the adrenal cortex hormones made?
all from cholesterol delivered via blood or made de novo which then use layer-specific enzymes to produce specific hormones
What is the first step in adrenal cortex hormone synthesis?
conversion of cholesterol to pregnenolone using cytochrome P450 side-chain cleavage via cholesterol desmolase (requires adrenodoxin reductase, NADPH, and O2)
NOTE: ALL layers of the cortex contain cholesterol desmolase (stimulated by ACTH)
What two things can happen to pregnenolone?
3B-hydroxysteroid dehydrogenase can form progesterone OR
17a-hydroxylase can form 17-hydroxy-pregnenolone
What can happen to progesterone?
21-hydroylase can turn it to 11-deoxy-corticosterone OR
converted to 17-hydroxyl-progesterone via 17a-hydroxylase
How is 11-deoxy-corticosterone transformed to aldosterone?
via 11B hydroxylase first to corticosterone and then
via aldosterone synthase (via a corticosterone intermediate) to aldosterone
What can happen to 17-hydroxy-pregnenolone?
3B-hydroxysteroid dehydrogenase can convert it to 17-hydroxyprogesterone OR
DHEA can be form (no enzyme)
What can happen to 17-hydroxyl-progesterone?
21-hydroxylase can convert it to 11-deoxy-cortisol OR
non-enzymatic conversion to androsterone (which then makes androgens testosterone and estradiol) NOTE: in males, adrenal androgens are of little significance since the testes produce their own testosterone but they are important in females
How is 11-deoxy-cortisol converted to cortisol?
NOTE: Cortisol is not absolutely necessary to sustain life is corticosterone can be made (i.e. in an isolated 17a hydroxylase deficiency)
What drugs inhibit glucocorticoid synthesis?
Metyrapone (11B-hydroxylase) and ketoconazole (cholesterol desmolase and other)
What regulates the secretion of ACTH?
CRH from the paraventricular nuclei in the hypothalamus acts on corticotrophs of the anterior pituitary via Gs mechanisms
How is the zona glomerulosa controlled?
It requires ACTH to produce aldosterone, but otherwise is under control of the renin system
How is cortisol released? What pattern? When?
It is released in a pulsatile manner, averaging about 10 bursts/24 hr with the highest rates occurring just before awakening (e.g. 8 am) and the lowest around midnight
NOTE: androgens and ACTH are secreted in similar patterns
How does cortisol regulate ACTH and CRH?
Feedback on both
What are the immediate effects of ACTH on the adrenal cortex?
stimulates transfer of stored cholesterol to the mitochondria to activate cholesterol desmolase
The diurnal pattern that drives CRH secretion can be abolished by what?
coma, blindness, or constant exposure to either light or dark
What isa dexamethasone suppression test?
dexamethasone is a synthetic glucocorticoid that mimics cortisol actions including stimulating negative feedback on ACTH secretion. Thus, the response to a low dose of dexamethasone should be .
This can be used to test whether hypercorticolism is due to an ACTH-secreting tumor (will not see decreased ACTH and cortisol with low dose, but will with a higher dose)) or a cortisol-secreting tumor (will not see decreased ACTH and cortisol with low or high dose)
What other things stimuate ACTH secretion?
decreased cortisol levels
stress, hypoglycemia, trauma
ADH or Serotonin
a-adrenergic agonists or B-adrenergic antagonists
What other things inhibit ACTH secretion?
opiods and somatostatin
When are aldosterone levels highest? Lowest?
Same as other adrenal cortex hormones in that it is diurnal, and highest right before awakening and lowest around midnight
How is aldosterone regulated?
angio II increases the synthesis and secretion of aldosterone by stimulating cholesterol desmolase and aldosterone synthase via Gq protein binding to AT1 receptors in the zona glomerulosa.
This occurs in response to a decrease in ECF volume causing decreased renal perfusion
What does aldosterone do?
stimulates Na+ reabsorption by the kidneys to help restore ECF Na+ content and ECF volume AND
reduces serum K+ and H+