Adrenocortical Hormones Flashcards
What are the 2 major parts of the adrenal gland?
outer thin cortex, inner medulla
What are the 3 zones in the adrenal cortex? What is each of the zone responsible for producing?
- zona glomerulosa: aldosterone
- zona fasciculata: glucocorticoids
- zona reticularis: sex hormones/ androgens
What is the primary controller for aldosterone secretion?
Angiotensin II
What is primary controller for glucocorticoid secretion?
ACTH
What’s the precursor for adrenocortical hormones?
Cholesterol, from plasma. Esterified once it enters the cell, and stored in lipid droplets
Which enzyme is required for cholesterol conversion to glucocorticoids/ androgens?
17-hydroxylase
Which of the adrenocortical hormone has the longest half life?
Cortisol - highly protein bound ~ 90min
Aldosterone, not as highly protein bound, ~ 20min
Which enzymes is responsible for the cleavage of cholesterol to pregnenolone?
cholesterol desmolase (rate limiting)
Where does the conversion of cholesterol to adrenal steroids occur?
mitochondria or ER
Where is adrenocortical hormone metabolized?
in the liver
conjugated to glucuronic acid. Freely soluble in plasma, excreted through urine
Which is the primary mineralocorticoid secreted by the adrenal cortex?
Aldosterone
What does 11-beta-hyddroxysteroid dehydrogenase type 2 have to do with mineralocorticoid activity?
This enzyme is found in the renal epithelium. It can convert cortisol to cortisone (cortisol has high affinity to mineralocorticoid receptors, but not cortisone)
In what circumstances can cortisol have a substantial mineralocorticoid effect?
when there is a congenital absence or inhibition of 11-beta-hyddroxysteroid dehydrogenase type 2 (when you eat too much licorice), then cortisol will have a substantial mineralocorticoid effect
What’s the MOA of aldoesterone?
Increased Na+ resorption, K+ excretion
- acts on the distal nephron –> collecting tubules/ducts (principal cells of the collecting tubules)
- bind to intracellular receptors
- increased # of Na/K ATPase on the basolateral membrame
- increased Na+ and K+ channels on the apical membrane
- net result = more Na+ back into the blood stream, and more K+ into the urine
What action doe aldosterone have on the intercalated cells in the cortical collecting tubules?
stimulates secretion of hydrogen in exchange for Na+
What other organs can aldosterone act on?
colon, sweat and salivary glands
How is aldosterone secretion controlled?
Angiotensin II directly stimulates the zona glomerulosa to secrete aldosterone
What stimulates the increase in angiotensin II?
activation of renin-angiotensin system
- when there is hypovolemic, hypotension
How does K+ concentration effect aldosterone?
increase in K+ concentration stimulates aldosterone secretion, leading to tubular K+ secretion
What’s the role of ACTH in aldosterone secertion?
If there is a chronic decrease in ACTH, aldosterone’s response to angiotensin II is diminished.
Acute increase in ACTH can increased aldosterone, but chronic increase in ACTH does not
What are some other factors that can affect aldosterone secretion?
Increase in Na+ can slightly decrease aldosterone.
Increase in atrial natriuretic peptide, can decrease aldosterone
What is the primary glucocorticoid secreted by the adrenal cortex?
cortisol
How does cortisol effect metabolis?
Protein: decreases extrahepatic update of amino acids, catabolic, and anti-anabolic
Liver: the increased amino acid in the blood is taken up by the liver, and converted to glucose and protein
How does cortisol effect blood glucose concentration?
- increase hepatic gluconeogenesis.
Gluconeogenesis and glycogenesis in the liver
- makes sure there is a supply of glucose for hormones such as glucagon and epinephrine to use - impair peripheral tissue uptake of glucose
Anti-insulin effect in muscles and adipose tissues
- excess cortisol = diabetogenic
How does cortisol affect fat metabolism?
has permissive effect on fatty acid mobilization during fasting
- allows other lipophilic hormones, such as growth hormone and epinephrine, to use fatty acids from lipid stores
How does cortisol influence inflammation and immunity?
- decreases inflammation –> inhibits phospholipase –> decreases synthesis of arachidonic acid, precursors for other pro-inflammatory molecules such as leukotriene, prostaglandins, and thromboxane
- stabilizes the lysosomal membranes –> decreases the release of proteolytic enzymes from damaged cells
- suppresses the immune system by suppressing T cells and antibodies
- inhibit fibroblastic activity
How is cortisol secretion controlled?
hypothalamus-pituitary axis –> CRH –> ACTH –> adrenal cortex
- ACTH has direct stimulatory action on the zona fasciculata (most important one) and zona reticularis
- ACTH increases conversion of cholesterol to pregnenolone, via cAMP 2nd messenger
- chronic ACTH stimulation –> hypertrophy and hyperplasia of the 2 zones, with sustained cortisol release
What’s the negative feedback mechanism for cortisol?
- free cortisol has direct negative feedback on the pituitary on ACTH release, and indirect CRH release
- ACTH release = diurnal (most in the morning, least at night)
How does stress influence ACTH?
High stress can override the cortisol negative feedback mechanism on ACTH release
- stressors stimulate the neuroendocrine cells of the hypothalamus to secrete CRH.
How are the symptoms of Addison’s explained?
Lack of both mineral and glucocorticoids
Decrease in mineralocorticoids:
- lack of Na retention –> hypotension, hypovolemia, hyperkalemia; mild acidosis
Decrease in glucocorticoids:
- abnormal fat, protein, and glucose metabolism –> muscle weakness, hypoglycemia, impaired utilization of fats for energy
- weight loss/ decreased appetite
- poor tolerance to stress –> Addisonian Crisis
What is aldosterone escape?
Even with excess amount of aldosterone, the Na+ retention will still only be transient. Increased Na+ will increased extracellular fluid volume and blood pressure, leading to pressure natriuresis and pressure diuresis , so the renal output of Na+ and water will be normal again despite excess aldosterone.
What happens if there is excessive aldosterone?
hypokalemia
when severe, can lead to muscle weakness
What happens if there no aldosterone?
- hyperkalemia –> cardiac toxicity
- normally, it would exchange K+ for H+ in the intercalated cells, too much K+ = little H+ = alkalosis
How does ACTH effect the zona glomerulosa?
ACTH –> binds to receptor on phospholipid bilayer –> activate adenylyl cyclase –> formation of cAMP in the cytoplasm –> activates other intracellular enzymes
- activate protein kinase A –> involved in the rate limiting step of formation pregnenolone from cholesterol
Which diuretic antagonizes the action of aldosterone?
spironolactone
