Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine > Glucocorticoid Synthesis > Flashcards

Glucocorticoid Synthesis Flashcards

1
Q

What are Glucocorticoids also called?

A

Corticosteroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do Glucocorticoids regulate?

A

Carbohydrate, Protein, and Fat metabolism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What effects do glucocorticoids have on metabolism?

A

Promote Gluconeogenesis.
Increase BG
Promote protein & fat catabolism in peripheral tissues.
“oppose insulin”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the primary glucocorticoid in man?

A

Cortisol (hydrocortisone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where is Cortisol synthesized?

A

Zona Fasciculata of Adrenal Cortex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the outermost zone of the adrenal gland called and what does it produce?

A

Zona glomerulosa

Aldosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the innermost zone of the adrenal gland called and what does it produce?

A

Zona reticularis

Androgens (DHEA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What controls synthesis of Cortisol and where does it come from?

A 
Adrenocorticotrophic hormone (ACTH)
Anterior Pituitary
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is ACTH secretion regulated?

A

by the Hypothalamus through corticotropin releasing hormone (CRH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is CRH and ACTH release inhibited?

A

By negative feedback through Cortisol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are glucocorticoids synthesized from?

A

Cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where is cholesterol obtained from?

A

Diet
Intracellular Cholesterol esters
Synthesis de novo in adrenals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where is cholesterol transported to for glucocorticoid synthesis?

A

Mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What enzyme cleaves the side chain of cholesterol to pregnenolone?

A

CYP11A1 (P450scc)

RATE LIMITING STEP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the reason for patients who are unable to produce ANY of the steroids?

A

They lack the CYP11A1 enzyme or the Cholesterol Transport Protein (StAR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is characteristic of congenital lipoid adrenal hyperplasia?

A

Lack Cortisol, Aldosterone, Testosterone, Estradiol.

Exhibit –> hyponatremia and hyperkalemia (salt wasting) Female genitalia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What converts pregnenolone to 17 alpha hydroxyprogesterone and androstenedione?

A

CYP17 ( steroid 17 alpha hydroxylase)

and 3beta-hydroxysteroid dehydrogenase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What happens when patients lack CYP17?

A

Unable to synthesize glucocorticoids and sex steroids.

  • Lack Cortisol, Testosterone, Estradiol
  • Exhibit elevated aldosterone levels –> Na retention and hypertension.
  • Lack of sexual development (phenotypic females) and inability to mature sexually.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why is CYP17 not required for aldosterone synthesis?

A

Because CYP17 is not expressed in zona glomerulosa where mineralcorticoids are synthesized.

-Lack of CYP17 causes increased production of aldosterone as glucocorticoids and sex steroids cant be made.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does CYP21 convert hydroxyprogesterone to?

A

11-deoxycortisol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

When patient lack CYP21 what happens?

A

Unable to synthesize aldosterone and cortisol. BUT can still make sex steroids.

-CYP21 not expressed in Gonads cause increased sex steroids in people who lack it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the most common form of Congenital Adrenal Hyperplasia (CAH)?

A

CYP21 Deficiency.

  • 1:14,000
  • Ranges from severe to mild
  • Require hydrocortisone replacement therapy, and in severe cases mineralcorticoid supplementation.
  • typically exhibit virilization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is virilization?

A

Masculinization/precocious puberty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does CYP11B1 (steroid 11beta-hydroxylase) convert 11-deoxycortisol to?

A

Cortisol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What happens when patients lack CYP11B1?

A

Unable to synthesize Cortisol.

-Aldosterone and Sex steroid synthesis remains intact b/c CYP11B1 is not expressed in Gonads and the Zona glomerulosa has a CYP11B2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What does CYP11B1 deficiency result in?

A
  1. Androgen Excess
  2. Aldosterone Excess in some patients - Na retention and hypertension.
  3. frequency of 1:250,000.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the principal mineralcorticoid?

A

Aldosterone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the role of Aldosterone?

A
  1. Regulates Na balance in body

2. Promotes K loss in urine in EXCHANGE for Na.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What does CYP11B2 do to Corticosterone to make Aldosterone?

A

Oxidizes C18 methyl group to aldehyde.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Where is the only place CYP11B2 found?

A

Zona glomerulosa of adrenal cortex (outermost zone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does a CYP11B2 deficiency cause?

A

VERY RARE

-Salt wasting (Na loss) but NO effect on cortisol or sex steroids.

32
Q

What and how much is cortisol bound to?

A

Plasma Proteins, 90% bound.

33
Q

What is characteristic of Corticosteroid Binding Globulin (CBG, Transcortin)?

A

High Affinity and Low Capacity.

-Normal conditions 80% of plasma cortisol is bound to CBG.

34
Q

What is characteristic of Albumin?

A

Low Affinity and High Capacity.

-normal conditions 10% of plasma cortisol is bound to albumin.

35
Q

What is the half life of Cortisol?

A

~100 min.

36
Q

What does reduction of the 4-5 double bond of cortisol cause?

A

Inactive Metabolites

-Can happen extra-hepatically or in the liver.

37
Q

What does reduction of the 3-keto group of cortisol cause?

A

Tetrahydrocortisol.

-Happens in the liver.

38
Q

What happens when Tetrahydrocortisol is conjugated at the 3-position?

A

Yields Glucuronide or Sulfate Metabolite.

-Excretion is via URINE.

39
Q

Where are synthetic glucocorticoids metabolized?

A

In the Liver.

-P450 mediated hydroxylations at various positions
(CYP3A4, 2C9, 2C19)
-Subsequent conjugation to glucuronic acid or sulfate.
-Biliary or renal excretion.

40
Q

What do steroids bind to and activate?

A

The Glucocorticoid Receptor.

41
Q

What is the action of the glucocorticoid receptor?

A

Either Increase or Decrease the Transcription of responsive genes.

-results in delayed onset of response (4-12hr)

42
Q

What may activation of the glucocorticoid receptor involve?

A

induction/activation of histone deacetylases.

43
Q

What does steroid binding to receptors cause?

A
  1. Release of heat-shock proteins
  2. Translocation of receptor to nucleus.
  3. Binding of receptor to GRE-sequences in promoter responsive genes, altering mRNA transcription.
44
Q

What are the required features of glucocorticoids?

A
  1. Ketone at C3 (3beta-HSD)
  2. Double bond at 4-5 of A ring (3beta-HSD)
  3. Hydroxyl at C11 (CYP11B1)
45
Q

Presence of a ketone at the C11 position on glucocorticoids is on what and what is required to activate to create a hydroxyl?

A

Prednisone, Cortisone

11Beta-Hydroxysteroid dehydrogenase (type1)

46
Q

Where is 11B-hydroxysteroid dehydrogenase (type 1) mainly found?

A

Predominantly in the liver.

47
Q

Which form of glucocorticoids is best for topical applications?

A

Hydroxylated

48
Q

Which form of glucocorticoids is best for patients w/ liver dysfunction or 11-HSD1 deficiency?

A

Hydroxylated

49
Q

What protects the kidney from Cortisol?

A

11B-Hydroxysteroid Dehydrogenase

50
Q

The mineralocorticoid receptor is ancestral to what receptor?

A

Glucocorticoid receptor.

-GR evolved from MR by gaining selectivity for cortisol.

51
Q

What does the mineralocorticoid receptor bind?

A

Aldosterone & Cortisol w/ equal affinity.

52
Q

Which receptor has selectivity for cortisol?

A

Glucocorticoid.

53
Q

What is the action of 11B-HSD (Type 2) in kidney cells?

A

Catalyzes oxidation of Cortisol to Cortisone.

  • Cortisone doesnt bind to MR or GR.
  • Protects renal tubule from circulating cortisol (more abundant than aldosterone)
54
Q

Where is the 11B-HSD (Type 2) found?

A

ONLY in aldosterone sensitive cells.

55
Q

Why is aldosterone not oxidized by 11B-HSD?

A

Because of the C-18 Aldehyde.

56
Q

What reactivates cortisone to cortisol and where?

A

11B-HSD (Type 1)

Liver

57
Q

What is a rare disease associated with deficiency in 11B-HSD?

A

Apparent Mienralcoritcoid Excess.

-HTN despite complete lack of aldosterone.

58
Q

What does licorice contain and what does it cause?

A

two compounds that inhibit 11B-HSD (type2) allows cortisol to stimulate MR resulting in HTN.

59
Q

What are the features which ENHANCE glucocorticoid potency/selectivity?

A
  1. Addition of a double bond at 1-2 position.
  2. Addition of a methyl group to C6
  3. Addition of a hydroxyl or methyl group of C16.
  4. Addition of a fluorine to C9.
  5. Combination of above.
60
Q

What does addition of a double bond at 1-2 do?

A

Enhances glucocorticoid potency 4-5 fold without affecting mineralocorticoid potency.

-Slows metabolism

61
Q

What are examples of glucocorticoids that have a double bond at 1-2 position?

A

Prednisone (Deltasone)

Prednisolone.

62
Q

What does addition of a methyl group to C6 do?

A

Further enhances glucocorticoid potency 1-2 fold and reduces mineralocorticoid potency by half.

63
Q

What are examples of glucocorticoids with a methyl group added to C6?

A

Methylprednisone/ Methylprednisolone (medrol)

64
Q

What does addition of a hydroxyl or methyl group at C16 do?

A

Enhances potency by 2.5 fold.

-Eliminates mineralocorticoid effect!!!

65
Q

What does addition of a Fluorine to C9 do?

A

Increases BOTH glucocorticoid (10 fold) and mineralocorticoid activity (125 fold)

-Used in Aldosterone replacement therapy.

66
Q

What is an example of a glucocorticoid with a Fluroine added to C9?

A

Fludrocortisone (Florinef)

67
Q

What does a combination of enhancing features do?

A

Yields highly potent glucocorticoids with NO mineralocorticoid activity.

68
Q

What are examples of glucocorticoids that have a combination of changes?

A
  1. Dexamethasone (Decadron)
  2. Triamcinolone (Aristocort)
  3. Betamethasone (Diprosone)
69
Q

What is an example of a short acting glucocorticoid?

A

Cortisol.

70
Q

What are examples of intermediate acting glucocorticoids?

A
  1. Prednisolone
  2. Methylprednisolone
  3. Triamcinolone
  4. Fludrocortisone
71
Q

What are examples of long acting glucocorticoids?

A
  1. Bethamethasone

2. Dexamethasone

72
Q

What is the G/M potency/activity of Cortisol?

A

1/1

73
Q

What is the G/M potency/activity of Prednisolone?

A

4/0.8

-1,2-ene

74
Q

What is the G/M potency/activity of Methylprednisolone?

A

5/0.5

-1,2-ene, C6-Me

75
Q

What is the G/M potency/activity of Triamcinolone?

A

5/0

-1,2-ene, C16-OH, 9-F

76
Q

What is the G/M potency/activity of Betamethasone and Dexamethasone?

A

25/0

-1,2-ene, C16-Me, 9-F

77
Q

What is the G/M potency/activity of Fludrocortisone?

A

10/125

-9-F

Endocrine (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions