Endocrine 07, 08 - Adrenal Steroid Hormones

Front 1

What is the precursor of all steroid hormones?

Back 1

Cholesterol.

Front 2

How is cholesterol transported from the liver to the adrenal gland (and gonads and placenta)?

Back 2

LDL.

Front 3

Name the 3 zones of the adrenal cortex (from capsule to medulla).

Back 3

1) Glomerulosa
2) Fasciculata
3) Reticularis

Front 4

Which steroid hormone is produced in the zona glomerulosa?

Back 4

Aldosterone (mineralocorticoids).

Front 5

Which steroid hormone is produced in the zona fasciculata?

Back 5

Cortisol (glucocorticoids).

Front 6

Which steroid hormones are produced in the zona reticularis?

Back 6

Androgens (DHEA, Testosterone, Estrogen, Androstenedione, Progesterone).

Front 7

What is the function of cortisol (glucocorticoids)?

Back 7

Increase plasma blood glucose by activating gluconeogenesis, and inhibiting insulin.

Front 8

What is the function of aldosterone (mineralocorticoids)?

Back 8

Increase Na+ retention and therefore water retention and blood pressure.

Front 9

What is the function of androgens?

Back 9

Development of secondary sexual characteristics, etc.

Front 10

To which cell layer does ACTH bind to in the adrenal cortex, and what is the ensuing product?

Back 10

Plasma membrane of cells in the zona fasciculata, producing cortisol.

Front 11

To what cell layer of the adrenal cortex will Angiotensin-II bind, and what steroid hormone will be produced?

Back 11

Zone glomerulosa, producing aldosterone.

Front 12

What is the rate-limiting step of cortisol, aldosterone, and DHEA biosynthesis, where does it occur, and by what enzyme?

What stimulates this conversion?

Back 12

Cholesterol --> pregnenolone.
Mitochondrial membrane.
Cyp450(scc).

ACTH.

Front 13

Which family of enzymes are critical in the formation of all steroid hormone biosynthesis?

Back 13

CypP450 enzymes, which hydroxylate intermediates.

Front 14

Steroid hormone products of the adrenal cortex are synthesized and secreted _________, not ________.

Back 14

on demand; stored.

Front 15

Which hormone secreted by the female ovaries, is only a transient intermediate in the adrenal cortex?

Back 15

Progesterone.

Front 16

Pregnenolone branches into what 2 products?

Back 16

1) Progesterone (transient)
2) DHEA - reticularis

Front 17

Progesterone branches into what 2 products?

What enzymes motivate this conversion?

Back 17

1) Aldosterone - glomerulosa
2) Cortisol - fasciculata

Cyp450 (c21 and c11 respectively)

Front 18

What effect does an increase in cortisol have on the hypothalamus/pituitary hormone pairs?

Back 18

Negative feedback control on the hypothalamus, decreasing CRH/ACTH release - and vice versa.

Front 19

What substrate is critical in the functioning of cortisol?

What enzyme facilitates this?

Back 19

11-OH group is critical for physiological activity.

Cyp450(c11).

Front 20

What is the effect of cortisone?

Back 20

Anti-inflammatory steroid.

Front 21

In aldosterone, what substrate-specific reaction occurs that is important for kidney action?

Back 21

Tying up the 11-OH group to form a hemiacetal.

Front 22

What is Congenital Adrenal Hyperplasia (CAH)?

Back 22

Deficient Cyp450(c21)
Block aldosterone and cortisol pathways
Back up the reticularis pathway
Increase androgen output (male sex hormones)

Front 23

What is the cause of Congenital Adrenal Hyperplasia (CAH)? What test is used to diagnose it?

Back 23

Deficient Cyp450(c21). Inject ACTH and observe a rise in 17-OH-Progesterone, which gets backed up when Cyp450(c21) is deficient.

Front 24

What are the clear clinical characteristics of CAH and in whom are they most clearly observed?

Back 24

Ambiguous genitalia and hirsutism seen clearly in female infants.

Front 25

Where are weak androgens converted to strong androgens?

Back 25

Liver, muscle, adipose tissue.

Front 26

What function do strong androgens play in the female?

Back 26

Major source of testosterone in females, maintain secondary sexual characteristics, are the sole estrogen precursors.

Front 27

Describe how cortisol is secreted by the adrenal cortex (in an unstressed individual)?

Back 27

Pulsatile bursts.

Front 28

What is significant about Pro-opiomelanocortin (POMC)?

Back 28

It derives into ACTH; ACTH production will also result in MSH and opioid formation.

Front 29

How does cortisol respond to different levels of stress?

Back 29

Major stress - cortisol rises steeply.
Minor stress - cortisol rises, but not as much.

Front 30

What stimulation test is used to confirm hypopituitarism with respect to the secretion of cortisol?

Back 30

Insulin injection will cause neither ACTH nor cortisol to rise in response to increased plasma glucose levels.

Front 31

How is cortisol transported in plasma?

Back 31

80% is bound to CBG (Cortisol Binding Globulin), 15% bound to albumin, and 5% is free and active.

Front 32

How is aldosterone transported in plasma?

Back 32

60% is bound to albumin (no globulin transporter), and the rest is free since it is more water soluble than cortisol.

Front 33

Between cortisol and aldosterone, which has a faster turnover rate?

Back 33

Aldosterone.

Front 34

Where are cortisol and aldosterone catabolized?

Back 34

In the liver.

Front 35

What structures of aldosterone and cortisol are preserved during catabolism?

Back 35

Steroid nucleus. Side groups are conjugated and inactivated for secretion.

Front 36

What molecule can be measured as an indicator of cortisol secretion?

Back 36

17-OH-corticoids.

Front 37

True/False: Cortisol is required for survival.

Back 37

True.

Front 38

What processes does cortisol stimulate?

Back 38

1) Liver gluconeogenesis
2) Fat lipolysis

Front 39

What hormone does cortisol block?

Back 39

Insulin.

Front 40

What counterintuitive process occurs during cortisol secretion?

Back 40

Glycogen synthesis. Cortisol causes some glucose to be released into the circulation, and some to store as glycogen.

Front 41

*Increased insulin will suppress gluconeogenesis and glycogenolysis. How will cortisol affect these processes?

Back 41

More insulin is required in the presence of cortisol for insulin to have the same effect.

Front 42

Increased insulin will increase glucose uptake from the circulation. How will cortisol affect this process?

Back 42

It will require more insulin to take up the same amount of glucose. Sometimes cortisol results in hyperglycemia.

Front 43

*How does cortisol affect host defense mechanisms?

Back 43

1) Supresses inflammation (cortisone), usually in response to long-term stress, by blocking phospholipase A2, which blocks the formation of leukotrienes and prostaglandins.
2) Suppresses immune response (block cytokine release, block fever cytokines, block T and B cell proliferation)

Front 44

True/False: Aldosterone is necessary for survival.

Back 44

True.

Front 45

How will the kidney respond to a low circulating blood volume and pressure?

Back 45

RAA pathway: Renin is released converting AT --> AT-I and ACE is released to convert AT-I --> AT-II.

Front 46

What are the main functions of AT-II?

Back 46

1) Regulation of aldosterone synthesis
2) Vasoconstriction

In response to low blood pressure/volume.

Front 47

What plasma ion concentration is critical in aldosterone regulation?

Back 47

Potassium.

Front 48

How is essential hypertension and edema typically treated?

Back 48

ACE inhibitors to lower the synthesis of aldosterone.

Front 49

How do steroid hormones act on the nucleus?

Back 49

Hormones bind to their receptors, which will transform into transcription factors and enter into the nucleus.

Front 50

*What types of dimers are formed by steroid hormone receptors as they act as transcription factors? How will they act on DNA?

Back 50

Homomeric dimers.

Induce transcription by recruiting RNA polymerase, but sometimes suppress it.

Front 51

Steroid hormone receptors may interact with transcription factors in 3 ways. Describe them.

Back 51

1) Homomeric dimer can bind to a positive HRE, inducing transcription.
2) Homomeric dimer can bind to a negative HRE, suppressing transcription.
3) Homomeric dimer can bind directly to the positive transcription factor itself, suppressing transcription.

Front 52

Describe how cortisol induces anti-inflammatory effects.

Back 52

Cortisol binding will induce the transcription of anti-inflammatory protein Lipocortin-1, which inhibits phospholipase A2, which blocks formation of leukotrienes and prostaglandins. An IL-1 antagonist will also form.
The pro-inflammatory TF NF-κβ is also inhibited.

Front 53

*What is the bodyguard protein (11β-HSD)?

Back 53

Due to the high structural similarity between cortisol and aldosterone, the bodyguard protein prevents cortisol from binding to aldosterone receptors, which would cause hypertension.

Front 54

What molecule will inhibit the bodyguard protein (11β-HSD)?

Back 54

Glycyrrhetinic Acid, GA, (found in licorice), and will induce hypertension.

Front 55

What is primary Cushing's Syndrome? What is its distinctive feature?

Back 55

An adrenal cortex adenoma or carcinoma resulting in hypersecretion of cortisol. The distinctive feature is a DROP in ACTH levels.

Front 56

What is secondary Cushing's Syndrome?

Back 56

Also known as Cushing's DISEASE, this is a hypersecretion of Cortisol due to moderately excessive pituitary output of ACTH.

Front 57

What is Ectopic ACTH Syndrome?

Back 57

Hypersecretion of cortisol due to increased ACTH from sources other than adrenal cortex or pituitary (lung cancer).

Front 58

What are the symptoms for Cushing's?

Back 58

Moon-shaped face, muscle wasting, increased facial hair, blood vessel thinning, thin skin.

Front 59

How would you differentiate a hypersecreting cortisol disorder?

Back 59

High Cortisol, Low ACTH - Primary Cushing's (adenoma)

If High Cortisol AND High ACTH:
High dose of DEX resulting in suppression of ACTH - Secondary Cushing's.
High dose of DEX resulting in NO suppression of ACTH - Ectopic ACTH Syndrome.
Low dose of DEX resulting in suppression rules out Cushing's.

Front 60

What is primary Addison's Syndrome?

Back 60

Also known as Addison's DISEASE, adrenal cortex (target organ) failure results in low levels of cortisol.

Front 61

What is secondary Addison's Syndrome?

Back 61

Deficiency in the pituitary gland, resulting in low cortisol levels.

Front 62

What is tertiary Addison's Syndrome?

Back 62

Deficiency in the hypothalamus, resulting in low cortisol levels.

Front 63

What are the symptoms for Addison's?

Back 63

High levels of ACTH and MSH (hyperpigmentation) in Primary Addison's.
Low levels of ACTH (pale skin and inability to tan) in Secondary and Tertiary Addison's.

Front 64

How do you test for Addison's?

Back 64

If plasma cortisol is low, administer ACTH to the adrenal cortex. No cortisol production - Primary Addison's.
Cortisol produced - Secondary or Tertiary Addison's.

Front 65

When do you measure cortisol?

Back 65

8 AM, when the level is highest.

Front 66

What hormone pair does an injection of insulin affect?

Back 66

CRH/ACTH will increase in a normal individual.

Front 67

What effect does cortisol have on the bone and connective tissue?

Back 67

Decrease bone formation and increase bone resorption; decrease connective tissue - typical in osteoporosis.