Mstn Ii - Lecture 24

Front 1

Steroid hormones are all made from:

Back 1

precursor cholesterol

Front 2

21 Carbons

Back 2

Pregnane nucleus (everything but Androgens, estrogens)

Front 3

19 Carbons

Back 3

Androstane nucleus (androgens)

Front 4

18 Carbons

Back 4

estrane nucleus (estrogens)

Front 5

No hydroxyl groups

Back 5

Progesterones

Front 6

Cortisol has OH at

Back 6

C11, C17, C21

Front 7

Aldosterone has OH at:

double bonded oxygen at:

Back 7

C11, C21

C19

Front 8

testosterone has OH at:

Back 8

C17

Front 9

Estrogen has:

Back 9

an aromatic ring (aromatase) which knocks off C18, which is why estrogens have 1 less carbon than androgens

Front 10

HMG-CoA reductase

Back 10

main regulated step of cholesterol synthesis

converts HMG-CoA into Mevalonate

inhibited by statin

Front 11

pregnenolone

Back 11

21C precursor for adrenal steroid synthesis

Front 12

P450scc (side chain cleavage)

Back 12

cleavage of cholesterol into pregnenolone

stimulated by increased levels of cAMP

inhibited by aminoglutethimide

Front 13

ZG (zona glomerulosa)

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makes mineralocorticoids - aldosterone

Front 14

glomerulosa controls the:

Back 14

glomerulus

Front 15

3β-hydroxysteroid dehydrogenase (3βHSD) Δ5-4 isomerase

Back 15

convert prognenolone to progesterone in the adrenal cortex

dehydrogenates C3 into a carbonyl group and moves the C5-6 double bond to C4-5

Front 16

1st step of Synthesis of Aldosterone

Back 16

Cholesterol -> Pregnenolone

P450 SCC

Front 17

2nd step of Synthesis of Aldosterone

Back 17

Pregnenolone -> progesterone

3betaHSD

Front 18

3rd step of synthesis of aldosterone

Back 18

Progesterone -> 11-deoxycorticosterone

21-hydroxylase

Front 19

4th step of synthesis of aldosterone

Back 19

11-deoxycorticosterone -> corticosterone

11beta-hydroxylase

Front 20

5th step of synthesis of aldosterone

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18 - hydroxydehydrogenase

Front 21

11-deoxycorticosterone

Back 21

weak mineralocorticoid

Front 22

21-hydroxylase

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make progesterone into 11-deoxycorticosterone

Front 23

corticosterone

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main glucocorticoid that acts in rodents

Front 24

11beta-hydroxylase

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converts 11-deoxycorticosterone into corticosterone in the mitochondria

mito enzyme

Front 25

18-hydroxylase and 19-hydroxydehydrogenase

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convert corticosterone into aldoterone

mito enzymes

Front 26

hydroxylases

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add OH

Front 27

hydroxydehydrogenases

Back 27

take off the hydrogen from an OH group

Front 28

progesterone

Back 28

precursor for aldosterone, cortisol, androgen synthesis.

kept in the adrenal cortex, so we do not have the effects of excessive progesterone production.

Front 29

Aldosterone is defined as a mineralocorticoid because:

Back 29

the double bonded oxygen at 19 protects the hydroxyl group at 11 from 11beta-HSD.

This is not the case with glucocorticoid.

Front 30

Primary regulatory mechanism of regulating aldosterone synthesis:

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via the renin-angiotensin system

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When there is low blood pressure, the kidney...

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release renin.

Front 32

Renin converts:

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angiotensionogin to angiotensin I, which is cleaved by ACE to form angiotensin II and III.

Front 33

Angiotensin II and III

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stimulate p450scc and 18-hydroxylase

This leads to increase of aldosterone synthesis.

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renal artery stenosis

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- narrowing of the artery decreases perfusion pressure downstream (in the kidney) leading to increased renin, etc.

- lead to high blood pressure

Front 35

Zona Fasciculate (ZF)

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makes glucocorticoid

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Major glucocorticoid in human:

major glucocorticoid in rodent:

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human: cortisol

rodent: corticosterone

Front 37

cortisol vs. corticosterone... why is one made and not the other?

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activity level of SER enzyme 17 alpha hydroxylase.

Front 38

17 alpha hydroxylase

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if levels are high: cortisol will be the major product

Front 39

zona glomerulosa (ZG)

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aldosterone is made

- does not have 17 alpha hydroxylase so corticosterone builds up.

- has 18 hydroxylase and 18 hydroxydehydrogenase

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18 hydroxylase and 18 hydroxydehydrogenase

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converts corticosterone to aldosterone

Front 41

Only difference between corticosterone and cortisol synthesis:

difference between the 2 molecules:

Back 41

17 alpha hydroxylase

presence of 17 -OH for cortisol

Front 42

CRH (hypothalamus)

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Corticotropin releasing hormone

increase POMC and ACTH

Front 43

POMC

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propiomelanocortin

precursor of ACTH

Front 44

ACTH (pituitary)

Back 44

adrenocorticotropic hormone

primary regulatory factor controlling cortisol synthesis

increase cortisol synthesis

Front 45

cortisol exhibits negative feedback:

Back 45

by binding to steroid receptors on the pituitary and hypothalamus to shut off CRH and POMC synthesis

Front 46

Once glucocorticoids are made, they can be:

Back 46

inactivated or cleared from the bloodstream by conjugation with glucuronic acid.

Front 47

ways to make glucocorticoids more hydrophilic so they no longer bind to their carrier molecules:

(2)

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- conjugate with glucuronic acid, which binds to an -OH group.

- get rid of the C3 carbonyl group as well as the double bond in ring A.

Front 48

11 beta HSD

Back 48

inactivate glucocorticoids

- get rid of the carbonyl on C19, so it can't form the hemiacetal form.

Front 49

Cortisol is long lasting because:

Back 49

is a stress hormone that helps with enduring stress

aldosterone is quick acting to retain sodium and water.
(lots in free form, not bound to carrier proteins)

Front 50

Zona Reticularis (ZR)

Back 50

makes androgens

most dehydroepiandrosterone (DHEA)

Front 51

dehydroepiandrosterone (DHEA)

Back 51

uses pregnenolone as a precursor

Front 52

17 alpha hydroxylase

C17-20 lyase

Back 52

required in the synthesis of androgens

Front 53

androstenedione synthesis:

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parallel pathway from progesterone via 17 alpha hydroxylase and C17-20 yase

Front 54

178 HSD

Back 54

convert androstenedione to testosterone.

Front 55

aromatase

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peripheral tissues (like fat) have aromatase which can aromatize testosterone into estrogens.

Front 56

ZR synthesis of androgens is controlled by:

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ACTH

Front 57

GC deficiency due to a destoryed ZF wil lead to:

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elevated androgen levels.

no GC or low levels of it leads to decreased negative feedback on ACTH. Thus ACTH levels increase to try to stimulate more GC synthesis and in the process, also stimulate androgen production as well.

Front 58

Addison's

Back 58

- patients appear tan due to increased ACTH production.
- ACTH has melanocyte stimulating activity as does its precursor, POMC.
- Hyperpigmentation occurs also around the gum area. When ACTh excess is due to an ectopic source (tumor), then the hyperpigmentation on the skin may be less and the nailbed may be darker.

Front 59

Cushing's

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- GC excess causes uncontrolled gluconeogenesis, which redeposits fat from the limbs to the trunk area.

- truncal obesity
- buffalo hump
- moon face
- red stripes called 'striae' on stomach

GCs are immunosuppressive, patients with Cushing's are prone to infection

Front 60

Conn's

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Mineralocorticoid excess leading to water retention and high blood pressure.

Front 61

21-hydroxylase deficiency

Back 61

- adrenal cortex is unable to make aldosterone, cortisol, or corticosterone.
- buildup of precursors which pushes toward teh androgen synthesis pathway leading to increased progesterone levels.

Front 62

low levels of 21-hydroxylase

Back 62

if levels are just low or the enzyme was mutated so the activity was low, this would increase ACTH levels resulting in eventually normal levels of aldosterone and cortisol but high levels of ACTH and androgen.