adrenocorticosteroids Flashcards by Monique Yuan

Where are the 2 adrenal glands located in relation to the kidney?

a) beside
b) in front
c) below
d) behind

a) beside

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What are the 2 main divisions/layers of the adrenal gland? Which one is the innermost layer?

1) cortex

2) medulla (innermost)

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What are the 2 main hormones that the adrenal medulla produces?

1) adrenaline

2) catecholamines/AA hormones

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What are the 3 zones/layers of the adrenal cortex?

1) zona glomerulosa
2) zona fasciculata
3) zona reticularis

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The adrenal cortex produces ____________ hormones.

steroid

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What is the common precursor for all adrenal steroid hormones?

cholesterol

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What are the 3 types of steroid hormones produced by the adrenal cortex? For each type of steroid hormone, provide: function, adrenal cortex zone that produces it, example hormone.

(hint: salt, sugar, sex)

1) mineralocorticoids (salt)
- salt balance
- zona glomerulosa
- aldosterone

2) glucocorticoids (sugar)
- metabolic and immune effects
- zona fasciculata
- cortisol

3) androgens (sex)
- act as precursor for strong androgens (testosterone) and estrogens
- zona reticularis
- DHEA (precursor androgen)

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What is the HPA axis? (i.e. what does it stand for?)

hypothalamus-pituitary-adrenal axis

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What response does the HPA axis control?

a) glucocorticoid response
b) mineralocorticoid response

a) glucocorticoid response

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HPA axis controls release of ________ from the zona ________.

cortisol, zona fasciculata

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in order of release from the hypothalamus –> anterior pituitary –> adrenal cortex, which is correct (HPA axis)?

a) CRH –> ACTH –> cortisol
b) cortisol –> ACTH –> CRH
c) ACTH –> CRH –> cortisol
d) cortisol –> CRH –> ACTH

a) CRH –> ACTH –> cortisol

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Does cortisol exert positive or negative feedback on CRH and ACTH?

negative feedback

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What is the function of cortisol?

immunosuppression

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What response does the RAAS system control?

a) glucocorticoid response
b) mineralocorticoid response

b) mineralocorticoid response

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What does RAAS stand for? (hint: which hormone does this system release?)

renin-angiotensin-aldosterone system

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What is the primary role of RAAS?

control blood pressure and blood volume

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what is the primary target organ of aldosterone?

kidneys

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Aldosterone promotes _______ and ________ reabsorption and ________ excretion.

Na+ and H2O reabsorption

K+ excretion

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What are the 4 steps of steroid hormone action?

1) hormone binds to unliganded receptor in complex with Hsp90 in CYTOPLASM
2) hormone dissociates from Hsp + is transported to nucleus
3) dimerized receptors interact with DNA and influence TRANSCRIPTION of TARGET GENES
4) GRE - glucocorticoid receptor/response element

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What are the 2 key targets of GR (glucocorticosteroid response/receptor) binding?

lipocortin and COX-2

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TRUE or FALSE: a given steroid has different affinities for either the glucocorticoid receptor or the mineralocorticoid receptor.

TRUE - steroids lie on a spectrum where one end represents high affinity to glucocorticoid receptor binding and the other end represents high affinity to mineralocorticoid receptor binding

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TRUE or FALSE: Cortisol can act on both the glucocorticoid receptor and the mineralocorticoid receptor, but it has a higher affinity for the glucocorticoid receptor.

FALSE - cortisol has EQUAL AFFINITY for both GC and MC receptors

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What enzyme is responsible for activating cortisol IN VIVO? what is the precursor of cortisol in vivo?

enzyme: 11-beta-hydroxysteroid dehydrogenase, type 1

cortisone –enzyme–> cortisol
ketone –enzyme–> hydroxyl

Explain why, even though cortisol has a 1:1 affinity for GC and MC receptors, it has weak MC effects IN VIVO?

kidney cells (MC targets) produce 11-beta-hydroxysteroid dehydrogenase, type 2, which DEACTIVATES cortisol

i.e. cortisol –enzyme–> cortisone

What is the difference between 11-beta-hydroxysteroid dehydrogenase, type 1 and type 2?

type 1: cortisone --> cortisol | type 2: cortisol --> cortisone

Which is the active form? a) prednisone b) prednisolone

b) prednisolone

Which one is more widely used (oral/injection)? a) prednisone b) prednisolone

a) prednisone

Which one has a strong topical effect? a) prednisone b) prednisolone

b) prednisolone

What is the structural difference between prednisone and prednisolone?

``` prednisone = ketone prednisolone = hydroxyl ```

1) TRUE or FALSE: prednisone is significantly metabolized by the liver and GC target tissues in order to become prednisolone. 2) What is the term used for this metabolism of a drug by the liver to become an active form of the drug?

1) TRUE | 2) first pass metabolism

Pseudohyperaldosteronism is caused by licorice overdose. Explain how this works.

- licorice contains an inhibitor of the an 11-beta-hydroxysteroid dehydrogenase, type 2 inhibitor (remember: type 2 inhibits cortisol binding to MC receptors) - this allows glucocorticoids like cortisol to bind to aldosterone target tissues (e.g. kidney), which is the WRONG EFFECT of cortisol IN VIVO - aldosterone increases Na and H2O reabsorption - reabsorption of Na and H2O results in high blood pressure

What is the genetic disease that results in pseudohyperaldosteronism? what causes this genetic disease?

apparent mineralocorticoid excess caused by mutation in 11-beta-hydroxysteroid dehydrogenase, type 2 gene

What is the overall metabolic effect of glucocorticoids? a) catabolic b) anabolic

a) catabolic

Do glucocorticoids increase or decrease circulating glucose?

increase

TRUE or FALSE: glucocorticoids lead to fat deposition in limbs but fat breakdown in the trunk.

FALSE - GC --> fat deposition in trunk + fat breakdown in limbs

Glucocorticoids cause a/an ___________ of muscle and bone mass in _________. a) loss; the trunk b) loss; the limbs c) gain; the trunk d) gain; the limbs

b) loss; the limbs

What is one term (2 words) that summarize the effects of fat/lipid balance as a result of glucocorticoid action?

"skinny fat"

What are the 2 key mechanisms in glucocorticoid anti-inflammatory effects?

1) glucocorticoids inhibit AA generation 2) glucocorticoids inhibit prostanoid synthesis note: these mechanisms cause DOWNSTREAM effects on inflammatory reactions

In the anti-inflammatory mechanism, glucocorticoids cause _______ suppression. a) COX-1 b) COX-2 c) COX-1 and COX-2

b) COX-2 suppression

Explain the mechanism of glucocorticoids in COX-2 suppression. (hint: what does COX-2 do?)

- COX-2 = inflammatory mediator - COX-2 metabolizes arachidonic acid to prostanoids - glucocorticoid suppresses TRANSCRIPTION of COX-2 GENE --> suppression of COX-2 expression on the PROTEIN levels

TRUE or FALSE: Glucocorticoid regulation of COX-2 involves direct receptor antagonism.

FALSE - glucocorticoids suppress COX-2 gene expression

Why does lipocortin induction by glucocorticoid receptor activation result in anti-inflammatory effects? (i.e. explain the mechanism)

- lipocortin has annexin A which has 2 anti-inflammatory roles: 1) direct effects on leukocytes --> inhibit tissue infiltration 2) suppression of phospholipase A2 (PLA2) activity --> prevent AA generation --> suppress generation of prostanoids

what is another name for lipocortins? why?

annexins --> lipocortins are characterized by annexin repeats

What causes Addison's disease? a) insufficient adrenocorticosteroids (GC and MC) b) excess adrenocorticosteroids (GC and MC)

a) insufficient adrenocorticosteroids

what are the 4 symptoms of Addison's disease?

1) fatigue 2) salt imbalance 3) sugar imbalance 4) skin discoloration

What drug is used to treat Addison's disease?

HYDROCORTISONE

Cushing's syndrome is caused by: a) insufficient adrenocorticosteroids (GC and MC) b) excess adrenocorticosteroids (GC and MC) c) excessive cortisol d) insufficient cortisol

c) excessive cortisol

What are the 4 causes of Cushing's syndrome?

1) adrenal tumor (cortisol-producing) 2) pituitary tumor (ACTH-producing) 3) drug induced 4) ectopic tumor (ACTH-producing)

What are the 3 symptoms of Cushing's syndrome?

1) round face 2) fat deposition in trunk 3) muscle loss, osteoporosis (protein and bone catabolism)

What is the treatment for Cushing's Syndrome?

- resect adrenal or pituitary tumor | - follow with gradual adjustment towards maintenance dose of CORTISOL

What are the main therapeutic effects of glucocorticoids?

1) anti-inflammatory 2) immunosuppressive 3) treat asthma 4) treat hematologic disorders

What is the metabolic side effects of glucocorticoids?

hyperglycemia

What is immunosuppressive side effects of glucocorticoids?

latent infections can emerge

What is the catabolic side effect of glucocorticoids?

osteoporosis and muscle wasting

what is the anti-inflammatory side effect of glucocorticoids?

slow wound healing and ulceration

TRUE or FALSE: glucocorticoids may lead to hypotension and psychosis.

FALSE - HYPERtension and psychosis

Why do you need to use tapering when stopping the long-term use of glucocorticoids? (i.e. what does abruptly stopping the use of GC lead to?)

- abruptly stopping GC --> Addison-like symptoms - this is due to negative feedback of GC administration on CRH and ACTH production - if you stop abruptly, body does not have time to readjust - therefore. tapering is necessary