Flashcards in Lecture 5: Hormonal Regulation of the Adrenal Cortex Deck (53):
What does ACTH stimulate in the end organ? What is the end organ?
Cortisol release by specific cell types in the adrenal cortex
What is the effect/main role of cortisol on the body?
Hyperglycemic hormone causing blood glucose to rise during stress response to ensure that organs called upon have the metabolic substrates necessary
What hormone has a similar structure to cortisol? What does this mean?
Cortisole can also bind mineralcorticoid receptors on kidney tubule to work with aldosterone synergistically
What is aldosterone generated by?
The renin-angiotensin-aldosterone system: produced by the outer section (zona glomerulosa) of the adrenal cortex in the adrenal gland
What is the function of aldosterone? How does it work?
It binds the mineralcorticoid receptors on the kidney tubule to promote sodium reabsoption and potassium secretion
What is the effect of cortisol on hypo and pit?
Describe the general cell composition of the adrenal cortex.
Heterogenous cell composition organized in layers
Describe the detailed cell composition of the adrenal cortex with the function of each layer.
1. Connective tissue capsule
2. Zona glomerulosa: where aldosterone is synthesized
3. Zona fasciculata: where cortisol is made
4. Zona reticularis: where androgens (DHEA and androstenedione) are synthesized
5. Medulla: irrelevant for this lecture
What is the precursor to all steroids?
What are the 2 functions of 21-α-hydroxylase?
1. Converts progesterone to 11-deoxycorticosterone (on aldosterone synthesis path)
2. Converts 17-α-hydroxyprogesterone to 11-deoxycortisol (on cortisol synthesis path)
What are the 2 functions of 11-β-hydroxylase?
1. Converts 11-deoxycorticosterone to
corticosterone (on aldosterone synthesis path)
2. Converts 11-deoxycortisol to cortisol
What happens when either 21-α-hydroxylase or 11-β-hydroxylase does not work properly? Would there be negative feedback back to hypo and pit?
The precursor substances are shunted to the androgenic pathway --> excess DHEA and androstenedione --> virilizing effects especially in women
No negative feedback so even more DHEA and androstenedione
What is virilization?
Masculinization is the biological development of sex differences
What are the 8 factors that stimulate ACTH secretion by the anterior pituitary and CRH secretion by the hypothalamus?
1. Cortisol decrease (either because of adrenolectomy or metyrapone)
2. Sleep-wake transition
4. Psychiatric disturbance (anxiety/depression)
6. β-adrenergic agonists
7. α-adrenergic antagonists
What is the effect of the drug metyrapone?
Blocks 11-β-hydroxylase => cortisol/aldosterone decrease
What are the 6 stressors that increase ACTH secretion by the anterior pituitary?
What is a pyrogen?
Substance, typically produced by a bacterium, that produces fever when released into the blood
Why does ADH stimulate ACTH secretion by the anterior pituitary?
Because there is a subpopulation of ADH-secreting neurons in
the paraventricular nucleus (the parvocellular neurons) that are co-localized with CRH-secreting
neurons. Therefore CRH and ADH are co-secreted into the portal vessels.
What are the 4 factors that inhibit ACTH secretion by the anterior pituitary? Which one is the strongest factor?
1. Cortisol increase: STRONGEST FACTOR
What 4 effects does cortisol have at baseline levels?
1. Glucose being stored as glycogen
3. Glucose being converted to lipids
4. Proteins being synthesized
What 4 effects does cortisol have at high concentration?
1. Glycogenolysis in liver
2. Inhibition of glucose uptake and glycolysis in resting muscles, lymphoids, adipose tissue, connective tissue
3. Increase in proteolysis in muscles, skin, and other tissues to liberate AAs in circulation for gluconeogenesis
4. Lipolysis to liberate free FAs to be converted to glucose OR ketones for energy (alternate source for the brain) and inhibition of lipid storage
Explain how the RAA system works. 6 steps
1. Drop in blood pressure/volume/sodium OR increase in potassium
2. Juxtaglomerular apparatus (JGA) in kidney releases renin into circulation
3. Renin converts angiotensinogen to angiotensin I
4. Angiotensin-converting enzyme (ACE) in vascular endothelium converts angiotensin I to angiontensin II
5. Angiotensin II binds to receptors on cells in the ZG of adrenal cortex to stimulate aldosterone production
6. Aldosterone acts on kidney tubules to stimulate sodium reabsorption to raise BP and potassium excretion to inhibit stimulation of aldosterone
What is the only organ in the body that sees 100% of the cardiac output?
What is the effect of high blood potassium on the adrenal cortex?
Stimulates aldosterone secretion
What causes Cushing's disease? 2 symptoms? 2 prolonged effects? Effect on water retention?
Caused by pituitary adenoma that releases excess ACTH: high cortisol levels
Symptom: purple striae on skin (similar to stretch marks) due to skin proteolysis of collagen and lipolysis in hips, thighs, and butt (not uniform) causing a redistribution of fat
Prolonged effects: insulin resistance and Type 2 diabetes because constant hyperglycemia and free FAs also trigger insulin causing a redeposition in fat store in belly and back of neck (buffalo hump)
Water retention increase: moon facies (puffy and round)
What can excessive water retention lead to?
What causes Cushing's syndrome? Symptoms? Treatment?
Cause is NOT pituitary adenoma but problem with adrenal gland (usually adrenal tumor)
Symptoms: same as Cushing's disease
Treatment: adrenal gland removal
How to diagnose Cushing's disease vs syndrome?
Cushing's disease: high ACTH and cortisol levels
Cushing's syndrome: low levels of ACTH and high cortisol levels
What is congenital adrenal hyperplasia (CAH) caused by? 2 options. Most common one? What does this cause? Symptoms? Treatment?
Deficiency in 21-α-hydroxylase (more common) OR 11-β-hydroxylase
Effect: Steroid hormone precursors are shunted toward the androgenic branch of the pathway and
cause excess production of DHEA and androstenedione + Low cortisol and low aldosterone: poor regulation of blood sugar and electrolyte balance
Symptoms: In women, you see virilization symptoms, suchas clitoromegaly (enlarged clitoris) and hirsutism (growth of excess body hair).
Treatment: glucocorticoid and aldosterone replacement therapy, which also provides negative feedback to hypothalamic-pituitary-adrenal axis causing a decrease in androgens
What can patients with very low cortisol experience in time of stress?
Vascular collapse: BP goes to 0, insufficient blood flow and nutrients to the brain, sometimes fatal
What causes Addison's disease? Treatment? Symptoms?
Autoimmune attack on adrenal cortex, which cannot produce cortisol nor aldosterone
Treatment: glucocorticoid and aldosterone replacement therapy
Symptoms: high ACTH, low BP, low blood glucose levels, potential vascular collapse, and very tan skin (palms, feet soles, and gums)
Why do Addison patients have very tan skin?
1. Lack of cortisol causes ACTH levels to rise
2. Breakdown of proopiomelanocortin (POMC) (to create ACTH) also produces α-melanocyte-stimulating hormone (α-MSH)
3. α-MSH stimulates melanocytes in the skin to produce pigment in response to UV
Where do most of the androgens in men come from?
Where do most of the androgens in women come from?
Why is aldosterone important during the stress response?
To increase blood flow to organs who need glucose during the stress response
How many AAs in ACTH?
What is the prepropetide of ACTH?
Proopiomelanocortin = POMC
What constitutes the first 13 AAs of ACTH?
α-melanocyte secreting hormone (α-MSH)
What is beta-endorphin? What is its function?
An other product of POMC breakdown
What is a common food supplement to boost testosterone levels?
What does DHEA stand for?
When does the single largest burst of cortisol blood levels occur? What is the purpose of this?
Ensures blood glucose is ready to feed your organs when you wake up
What are adrenergic receptors?
Sympathetic NS receptors that are G protein-coupled receptors and targets of the catecholamines, especially norepinephrine and epinephrine
What is adrenaline?
Difference between alpha and beta adrenergic receptors?
Alpha receptors: stimulation and constriction of blood vessels, orgasms, pupil dilation, growth
Beta receptors: relaxation and dilatation of blood vessels, heart rate increase, reduction of gut motility, dilation of lungs, insulin secretion
What are enkephalins?
Breakdown product of POMC
What kind of feedback loop is the one exerted by enkephalins on CRH/ACTH secretion?
Short-loop negative feedback
What organ produces ACE?
Does aldosterone negatively feedback on hypo and pit?
List the 7 molecules that result from the breakdown of POMC.
Where are androgens produced?
What hormone is ACTH similar to? What does this mean?
alpha-MSH, so can bind to its receptors when in excess and cause tanning of skin