Adrenal Physiology

Question 1

Epinephrine and Norepinephrine are known as __________, which are rapid-response stress hormones secreted from the _______. These are _______ -derivatives. Steroids are ____ response hormones produced by the ________. These are ______-derivatives.

Answer 1

Catecholamines = rapid-response stress hormones made in adrenal medulla = Tyrosine-derivatives.
Steroids = slow-response hormones from the adrenal cortex = Cholesterol-derivatives.

Question 2

Describe what each layer of the adrenal cortex produces.

Answer 2

Zona glomerulosa (salt) makes mineralocorticoids, Zona fasciculata (sugar) makes glucocorticoids and the Zona reticularis (sex) makes androgens from cholesterol precursors.

Question 3

The specialized post-synaptic sympathetic ganglia in the medulla are ________ cells. Name at least 3 stimuli that trigger the release of their products.

Answer 3

Chromaffin cells (specially stained) secrete catecholamines in response to hunger, dehydration or a fight-or-flight scenario.

Question 4

What catecholamine is greater in quantity in the presence of cortisol?

Answer 4

Epinephrine is in greater quantity than Norepinephrine since cortisol stimulates the converting enzyme PNMT.

Question 5

The sympathetic stimulation of what enzyme can trigger the conversion of Tyrosine to DOPA in the catecholamine biosynthesis pathway?

Answer 5

Tyrosine hydroxylase enzyme

Question 6

Beta-adrenergic receptors are more responsive to ________. Name at least 5 actions that they are responsible for.

Answer 6

Epinephrine @ Beta receptors;

Lipolysis, increased heart rate, inotropy, arteriolar dilation, low BP at skeletal muscles and bronchioles

Question 7

Alpha-adrenergic receptors are more responsive to __________. Name at least 3 actions that this stimulation is responsible for.

Answer 7

Norepinephrine @ alpha-receptors;

Arteriolar vasoconstriction, glycogenolysis and increased BP at the visceral organs, kidneys and genitalia

Question 8

Name some common uses of catecholamines agonists. Provide an example drug.

Answer 8

Amphetamines, for example, are nasal decongestants, appetite suppressors, stimulants, bronchodilators (to treat asthma)

Question 9

Name some common uses of catecholamine antagonists.

Answer 9

Lower blood pressure, treat anxiety, treat abnormal cardiac rhythms. An example would be a Beta-blocker.

Question 10

Briefly describe the 5 events that occur in the biosynthesis of steroid hormones. Put an (*) next to the rate-determining step.

Answer 10

1. Cholesterol binds LDL receptor or is made in situ via Acetyl-CoA.
2. Cholesterol is sterilized and hydrolysis to be transported into outer membrane of mitochondria (mt)
3. RDS Cholesterol is converted into Pregnenolone via CYP11A enzyme.
4. Pregnenolone is transported out into E.R. To be modified via hydroxylations.
5. End products diffuse out of the cell and into the bloodstream to be distributed to effector tissues.

Question 11

What determines what biosynthetic pathway pregnenolone travels down to form steroid end-product?

Answer 11

Depending on the layer of the adrenal gland.

Question 12

The adrenal cortex is pivotal in the production of androgens for what sex?

Answer 12

A.C. Is important for androgen production in females, since males have testes that play a major role in that function.

Question 13

The zona ______ lacks CYP17 enzyme to make _________. This differs form the zona fasciculata and reticularis that make ______ and _____.

Answer 13

Zona glomerulosa makes Aldosterone. ZF and ZR have CYP17 enzyme to produce DHEA and androgens.

Question 14

The up-regulation of what 3 enzymes can stimulate cortisol production.

Answer 14

1. CYP11A
2. Steroidogenic Acute Regulatory Protein (StAR)
3. CYP17 enzyme

Question 15

In regards to the circadian rhythm, when does the highest level of cortisol secretion occur? What is its significance on ACTH? How does it affect appetite and blood sugar levels?

Answer 15

In the early morning at about 6-7 AM, cortisol and ACTH levels rise. As cortisol builds, it inhibits ACTH secretion via negative feedback. Cortisol is a potent stimulator of appetite and helps normalize blood sugar levels throughout the day.

Question 16

What effects does Corticosteroid-binding globulin (CBG) have on Cortisol? What significance does it have for a chronically stressed individual?

Answer 16

CBG serves as a mobile reservoir and protects cortisol from degradation. By doing this, it extends its half-life in the body which is why a chronically-stressed person, stimulated by ACTH, can have a 50-fold increase in cortisol levels.

Question 17

What enzyme is responsible for keeping active cortisol at equilibrium with it’s inactive analog? What are the 2 types and where can they be found?

Answer 17

The 2 types of 11-HSD (11-Beta hydroxysteroid dehydrogenase) keeps cortisol levels at equilibrium between active and inactive forms. Type 1 produces the ACTIVE cortisol and is found in multiple tissues such as in bone and the pituitary gland. Type 2, however, makes the INACTIVE form and can only be found in the kidney and other aldosterone target tissues.

Question 18

How does kidney failure relate to high levels of cortisol in circulation?

Answer 18

Kidney failure results in a loss of Type 2 11-HSD enzyme which would increase cortisol levels. This is because it normally keeps cortisol levels in check by forming the inactive cortisone.

Question 19

What is a good clinical marker cortisol?

Answer 19

The presence of Glucouronides in urine is a better clinical marker of cortisol than cortisol from drawing blood.

Question 20

Describe 3 major effects that excess cortisol has on the body.

Answer 20

1. Increases lipogenesis in face, trunk, neck and abdomen.
2. Increase appetite thus increasing caloric intake.
3. Reduced Insulin uptake of glucose = elevated blood sugar levels.

Question 21

How does cortisol work against insulin and why does it trump its effect?

Answer 21

Cortisol maximizes glucose production and minimizes glucose uptake, which opposes insulin’s functions. It’s posited to be more effective against insulin, since glucose is needed in the brain (as an obligate energy source) more than in muscle when the body is stressed out.

Question 22

Describe the mechanism by which cortisol is anti-inflammatory.

Answer 22

Cortisol inhibits enzymes phospholipase and cyclooxygenase which reduces lymphocyte migration and vasodilation, respectively. Therefore, it impairs the vascular component of inflammation.

Question 23

Why does Cortisol inhibit immune and inflammatory responses?

Answer 23

Suppressing the immune response shuts down non-required functional activities that allows the body to better deal with stress. Cortisol plays a co-regulatory role to make sure that conditions of autoimmunity or chronic inflammation does not get out of control.

Question 24

What are cortisol’s 2 effects on an immune response?

Answer 24

1. Cortisol inhibits production of interleukin-1 (antigen) from macrophages which reduces the recruitment of T cells.
2. it also inhibits interleukin-2 which reduces the secondary proliferation of helper and suppressor T-cells.

Question 25

What effects does Aldosterone have on K+ and Na+?

Answer 25

Aldosterone results in Na+ retention to which water follows to increase Blood volume and BP. It also promotes excretion of K+ into sweat, urine and feces.

Question 26

In what cases, would cortisol be involved in the RAAS system to replace Aldosterone’s function?

Answer 26

Kidney failure, rare mutational loss of Type 2 11-HSD enzyme or hyperadrenal disorders can overwhelm the kidney and impair the ability to deactivate cortisol. For instance, Cushing’s disease may impair this, as 80% of patients present with hypertension.

Question 27

List at least 5 major signs/symptoms associated with Cushing’s Disease.

Answer 27

Obesity (with fat deposits at the face, neck and abdomen), muscle atrophy, osteoporosis, HTN, insulin resistance.

Question 28

List at least 5 major signs/symptoms associated with Addison’s Disease.

Answer 28

Loss of appetite (weight loss), fatigue, insulin sensitivity, hypotension & HYPER-pigmentation

Question 29

Why is hyperpigmentation correlated to Addison’s disease?

Answer 29

Hyperpigmentation is associated with primary Addison’s disease since there is a deficiency with negative feedback in the hypothalamus and pituitary gland. This leads to an XS production of ACTH that adversely impacts pre-pro-opio-melanocortin (POMC) that stimulates melanocytes.

Question 30

List at least 3 methods used to manage the symptoms of Cushing’s Disease.

Answer 30

1. Dietary changes: increase Ca++ and Vitamin D, decrease Na+
2. HTN: thiazides (Ca++ sparing) and Amiloride (K+ sparing)
3. Steroid-hormone inhibitors (metropole; drawback = hypogonadism)
4. Glucocorticoid antagonist (Mifepristone)

Question 31

Name one effective way to manage/treat Addison’s Disease.

Answer 31

Prednisone supplement as a synthetic agonist of the low levels of endogenous cortisol. It is 4x as effective as cortisol in glucocorticoid use.