12.01.17 Adrenal steroids

Question 1

Name the layers of the adrenal cortex and their products (3):

Answer 1

• Zona glomerulosa: aldosterone
• zona fasciculata: cortisol, corticosterone
• zona reticularis: DHEA

Question 2

In the adrenal cortex, cholesterol is converted to pregnenolone by _____. Corticosterone is converted by ____ to aldosterone. This enzyme is found only in the ____ of the adrenal cortex.

Answer 2

In the adrenal cortex, cholesterol is converted to pregnenolone by ACTH. Corticosterone is converted by aldosterone synthase to aldosterone. This enzyme is found only in the zona glomerulosa of the adrenal cortex.

Question 3

Two types of corticoid receptors exist:

• type I: _____ receptor, it has high affinity for ____ and ____. Present in CNS, kidney and gut.
• type II: _____ receptor, it binds ____ but much lower affinity for ____. Present in nearly all tissues.

Answer 3

Two types of corticoid receptors exist:

• type I: mineralocorticoid receptor, it has high affinity for cortisol and aldosterone. Present in CNS, kidney and gut.
• type II: glucocorticoid receptor, it binds cortisol but much lower affinity for aldosterone. Present in nearly all tissues.

Question 4

Mineralocorticoids promote ____ reabsorption in the kidneys.

Answer 4

Mineralocorticoids promote sodium reabsorption in the kidneys.

Question 5

Glucocorticoids stimulate ____ in the liver, which increases plasma ____. It also increases ____ secretion. It can also decrease glucose uptake by muscle and other tissues, except ____ tissue. Increase release of ____ from muscle and increase release of ____. It can decrease ____ synthesis and increase its degradation.

Answer 5

Glucocorticoids stimulate gluconeogenesis in the liver, which increases plasma glucose. It also increases insulin secretion. It can also decrease glucose uptake by muscle and other tissues, except brain tissue. Increase release of amino acids from muscle and increase release of fatty acids. It can decrease collagen synthesis and increase its degradation.

Question 6

Mineralocorticoids primary site of action is in the ____ of the kidney. It promotes ____ retention and ____ elimination. ____ retention leads to ____ retention. Increased aldosterone is secreted in response to decreased ____ levels and ____.

Answer 6

Mineralocorticoids primary site of action is in the distal tubules of the kidney. It promotes sodium retention and potassium elimination. Sodium retention leads to water retention. Increased aldosterone is secreted in response to decreased sodium levels and BP.

Question 7

Outline the mechanical steps of aldosterone at the distal tubule.

Answer 7

1. Aldosterone binds to nuclear receptor
2. Hormone-receptor complex translocates to nucleus
3. Transcription, translation of new proteins
4. New channels and pumps made and existing channels and pumps modified to modulate activity
5. Net effect is increased sodium reabsorption and increased potassium secretion

Question 8

HSD2 (11β-Hydroxysteroid dehydrogenase) inactivates ____, but not ____ in kidney tubules. HSD2 is inhibited by glycyrrhetinic acid in licorice.

Answer 8

HSD2 (11β-Hydroxysteroid dehydrogenase) inactivates cortisol (to inactive cortisone), but not aldosterone in kidney tubules. HSD2 is inhibited by glycyrrhetinic acid in licorice.

Question 9

The zona glomerulosa is not activated by ___ secreted by the pituitary. The ____ system stimulates production of aldosterone.

Answer 9

The zona glomerulosa is not activated by ACTH secreted by the pituitary. The renin-angiotensin system stimulates production of aldosterone.

Question 10

Increased blood plasma ___ levels stimulate the zona glomerulosa to release ____. The atria of the heart secretes ____ (ANP), a hormone used to monitor high BP.

Answer 10

Increased blood plasma potassium levels stimulate the zona glomerulosa to release aldosterone. The atria of the heart secretes atrial natriuretic peptide (ANP), a hormone used to monitor high BP.

Question 11

The primary endogenous glucocorticoid is ____, which increases the concentration of plasma ____ at the expense of fat and proteins in a process called ____.

Answer 11

The primary endogenous glucocorticoid is cortisol, which increases the concentration of plasma glucoseat the expense of fat and proteins in a process called gluconeogenesis.

Question 12

The liver breaks down ___ into ___ to maintain blood glucose levels. When depleted, new glucose is made from (3):

Answer 12

The liver breaks down glycogen into glucose to maintain blood glucose levels. When depleted, new glucose is made from (3): lactate, glycerol and glucogenic amino acids (serine and alanine)

Question 13

The brain can only function using ___ or ___ for energy. It takes time to break down fat in time to supply brain.

Answer 13

The brain can only function using glucose or ketone for energy. It takes time to break down fat in time to supply brain.

Question 14

Cortisol:

• ___ glucose utilization by cells everywhere in the body except ___.
• stimulates ____ degradation in all cells except liver cells
• ___ lipolysis or release of fatty acids into the blood. FFA can be converted to ketone bodies by the liver.

Answer 14

Cortisol:

• decreases glucose utilization by cells everywhere in the body except brain.
• stimulates protein degradation in all cells except liver cells
• increases lipolysis or release of fatty acids into the blood. FFA can be converted to ketone bodies by the liver.

Question 15

Lipocortin inhibits ____, which converts phospholipids to arachidonic acid.

Answer 15

Lipocortin inhibits phospholipase A, which converts phospholipids to arachidonic acid.

Question 16

Glucocorticoid block ___ migration out of blood vessels by (2):

Answer 16

Glucocorticoid block neutrophil migration out of blood vessels by (2):

• inhibit response to chemotactic molecules
• prevent passage through endothelial gap junctions

Question 17

Glucocorticoids inhibit tissue destruction by ____ by blocking their activation and release of proteases like collagenase, elastase and plasminogen activator.

Answer 17

Glucocorticoids inhibit tissue destruction by macrophages by blocking their activation and release of proteases like collagenase, elastase and plasminogen activator.

Question 18

List a few reasons why corisol might be released in response to stress:

Answer 18

• Heightened brain function necessary (get glucose to brain)
• Maintenance of vascular response to NE for “flight”
• Suppression of self-healing mechanisms that divert energy (eg. inflammation and immunity)
• pain suppression

Question 19

Outline the feedback control of cortisol release in HPA axis

Answer 19

Hypothalamus releases CRH–>anterior pituitary release ACTH–>adrenal gland releases cortisol

*negative feedback look with cortisol inhibiting anterior pituitary and hypothalamus

Question 20

Adrenocortical Insufficiency (Addison’s Disease) is separated into primary and secondary:

• primary: characterized by ____ dysgenesis, or destruction/atrophy
• secondary: inadequate secretion of ____ (hypopituitarism, gucocorticoid receptor deficiency), prolonged treatment with ____

Answer 20

Adrenocortical Insufficiency (Addison’s Disease) is separated into primary and secondary:

• primary: characterized by adrenal gland dysgenesis, or destruction/atrophy
• secondary: inadequate secretion of ACTH (hypopituitarism, gucocorticoid receptor deficiency), prolonged treatment with corticosteroids

Question 21

Symptoms of adrenocortical insufficiency include (6):

Answer 21

– fatigue & weakness
– anorexia, nausea, weight loss
– poor blood glucose regulation
– hypotension
– can lead to severe volume depletion and shock
– inability to cope with stress

Question 22

95% of cases of congenital adrenal hyperplasia (CAH) are due to ____ deficiency. A nonfunctional allele of ____ in the genome leads to recombination and mutation of the gene.

Answer 22

95% of cases of congenital adrenal hyperplasia are due to 21α-hydroxylase deficiency. A nonfunctional allele of CYP21B in the genome leads to recombination and mutation of the gene.

Question 23

Symptoms vary with 21α-hydroxylase deficiency:

• Severe: ____ CAH, life-threatening ___ and ___ during first weeks of life.
• Moderate: simple ____ CAH, causes ___ in prepubertal children
• Mild: ____ CAH, cause androgen effects and ___ in adolescent and adult women.

Answer 23

Symptoms vary with 21α-hydroxylase deficiency:

• Severe: salt-wasting CAH, life-threatening vomiting and dehydration during first weeks of life.
• Moderate: simple virilizing CAH, causes virilization in prepubertal children
• Mild: non-classical CAH, cause androgen effects and infertility in adolescent and adult women.

Question 24

Remaining 5% of cases of congenital adrenal hyperplasia are due to mutations in (4):

Answer 24

– 11β-hydroxylase
– 17α-hydroxylase
– 3β-dehydrogenase
– StAR

Question 25

Adrenocortical hyperfunction (Cushing’s syndrome) results from ____ levels, manifesting in ___ decade. Causes can include ___ adenomas or be result of pharmacologic causes (___ or ___ administration)

Answer 25

Adrenocortical hyperfunction (Cushing’s syndrome) results from continued high glucocorticoid levels, manifesting in 3rd-6th decade. Causes can include pituitary or adrenal adenomas or be result of pharmacologic causes (glucocorticoid or ACTH administration)

Question 26

List a few signs of Cushing’s syndrome:

Answer 26

– moon face (subcutaneous fat deposition)
– buffalo hump
– central obesity (fat is deposited in the body trunk)
– extremity thinning and atrophy
– glaucoma and cataract formation
– brittle bones
– hirsutism and masculinization
– blood-glucose levels rises chronically (may cause pancreatic beta cells to die, causes adrenal diabetes)

Question 27

Therapeutic uses of adrenal corticoids include (4):

Answer 27

• Replacement Therapy
– Adrenocortical insufficiency
– Congenital adrenal hyperplasia 
• Diagnosis of Cushing’s syndrome •
 Anti-inflammation treatment 
• Cancer chemotherapy