Biochem 3: Adrenals

Question 1

cholesterol derivative hormones are what type of hormones

Answer 1

steroid hormones

Question 2

in which part of the adrenals are steroid hormones made

Answer 2

the cortex

Question 3

Which hormones are created where in the adrenal cortex?

Answer 3

Zona glomerulosa: mineralocorticoids (aldosterone)
Zona fasciculata: glucocorticoids (cortisol)
Zona reticularis: androgens (DHEA

Question 4

What type of hormones are located in the medulla, name the 3 hormones too?

Answer 4

catecholamines from tyrosine

NE, Epi, Dopamine

Question 5

Explain how ACTH is important in synthesis of adrenal cortex hormones

Answer 5

Starts the cascade effect of hormone production when ACTH (released from AP) acts on the Gs (cAMP) receptor

Question 6

What is the cascade effect in synthesis of adrenal cortex hormones

Answer 6

ACTH bind to Gs receptor –> activate PKA –>activate lipase.

Lipase then cleaves cholesterol esters to free cholesterol.

Free cholesterol is converted to the different hormones via mitochondrial reactions

Question 7

what are steroid carrying proteins

Answer 7

proteins that are important in transporting steroid hormones to distant sites

Question 8

why are steroid carrying proteins so important

Answer 8

steroid hormones are hydrophobic and so they must be attached to a protein

Question 9

GIve an example of steroid carrying proteins

Answer 9

Cortisol binding protein/globulin
it carries:
1.cortisol
2. aldosterone

Question 10

CBP is produced in the adrenals TRUE or FALSE

Answer 10

FALSE; they are produced in the liver

Question 11

whats the point of cortisol-cortisone shunt

Answer 11

to prevent cortisol from binding to mineralocorticoid receptor (MR)

the concentration of cortisol is 1000x greater than aldosterone, which allows it to easily bind with MR causing AME

Question 12

What happens when cortisol binds with MR

Answer 12

Apparent mineralocorticoid excess (AME)

• Conn Syndrome like effect – hyper-aldosteronism
• cortisol can activate MR so with a 1000x concentration of cortisol, its going to active it

Question 13

what 2 hormones can bind to MR

Answer 13

cortisol and aldosterone

Question 14

So how does the shunt prevent cortisol from binding with MR

Answer 14

converts cortisol into cortisone

cortisone can’t bind with MR receptor.

Question 15

what 2 enzymes are involved in activating and inactivating cortisol

Answer 15

11B-HSD2 - inactivator of cortisol in the KIDNEY (cortisol–> cortisone)

11B-HSD1 - activator of cortisol in the LIVER (cortisone–>cortisol)

Question 16

what is so special about the skin

Answer 16

has 11B-HSD1; allows cortisone cream to convert to cortisol (active form)

Thats why topical is effective

Question 17

What is interesting about licorice

Answer 17

contains glycyrrhizic acid which INHIBITS 11B-HSD2.

this allows cortisol access to MR which leads to HTN and hypokalemia

Question 18

What is the role of CYP450 in steroid hormones

Answer 18

convert free cholesterol to metabolite pregnenolone

Question 19

Pregnenolone is needed …

Answer 19

for the production of all steroids: mineralocorticoids, glucocorticoids, androgens

Question 20

which enzyme catalyzes cortisol and androgen

Answer 20

CYP17

Question 21

which hormones do CYP21 catalzye

Answer 21

cortisol and mineralocorticoids

Question 22

TRUE or FALSE; if theres a deficiency in one of the enzymes it will shift production of steroids to the other pathway

Answer 22

TRUE

if CYP21 is deficient –> coritsol and mineralocorticoid isn’t produced but since CYP17 still works androgen will be produced

Question 23

TRUE or FALSE; cortisol needs either pathway to work in order to be produced

Answer 23

FALSE; it needs the activity of BOTH CYP17, 21 (and 11)

Question 24

what is Cushing Syndrome

Answer 24

excess cortisol for any reason

Question 25

what is Cushing Disease

Answer 25

limited to pituitary adenoma --> increased ACTH levels

Question 26

Cushing Syndrome can be classified on LOCATION OF PRODUCTION

Answer 26

Endogenous: w/in the hypothal, pit, or adrenal axis Exogenous: source outside the body (DRUGS)

Question 27

Cushing Syndrome can be classified on LOCATION OF LESION

Answer 27

Primary: abnl in the ADRENAL gland --> increased cortisol prodcution Secondary: abnl in the PITUITARY gland --> increased cortisol level - typically by increasing ACTH levels

Question 28

What are the 4 symptoms of Cushing Syndrom

Answer 28

1. HTN 2. Weight gain 3. Wound 4. Muscle wasting

Question 29

What is Addison Disease

Answer 29

progressive destruction of adrenal gland ---> decreasing steroid synthesis

Question 30

What will you see with the hormone levels

Answer 30

LOW cortisol and aldosterone

Question 31

What are the symptoms of Addison Disease

Answer 31

Hyperpigmentation Hyponatremia Hyperkalemia

Question 32

Explain how hyperpigmentation arises in Addison

Answer 32

low cortisol levels --> increase ACTH levels | ACTH release is associated with increases in MSH --> increased MSH --> hyperpigmentation

Question 33

which hormone is responsible for hyponatremia and hyperkalemia in Addison

Answer 33

Low Aldosterone

Question 34

What is congenital adrenal hyperplasia

Answer 34

a block in corticosteroid synthesis bc of defect in CYP21 --> leading to shunting into ANDROGEN (CPY17) increased androgen

Question 35

what are the symptoms of CAH

Answer 35

virilization in females --> too many androgens (ambiguous genitalia) hyperkalemia, hyponatremia, and wegith loss --> NO ALDOSTERONE --> salt and water loss

Question 36

what is apparent mineralocorticoid excess (AME)

Answer 36

cortisol binds to MR -->mimics high ALdosterone levels --> hypokalemia, hypernatremia --> HTN

Question 37

which enzyme is defective in AME

Answer 37

11B-HSD2 in the kidney (cortisol --> cortisone)

Question 38

How are catecholamines synthesized

Answer 38

phenylalanine --> L-Tyrosine --> Dopa --> Dopamine --> NE --> Epi

Question 39

TRUE or FALSE: neurons make both NE and Epi

Answer 39

FALSE; neurons make up to NE and ADRENAL MEDULLA makes Epi

Question 40

what 2 enzymes metabolize catecholamines

Answer 40

MAO (monoamine oxidase) | COMT (cathechol -O-methyl transferase)

Question 41

what do the catecholamine eventually break down to

Answer 41

vanillylmandelic acid, VMA | aka 3-methoxy-4-hydroxymandelic acid

Question 42

where can you find VMA

Answer 42

excreted in the urine and also seen in teh blood

Question 43

what is pheochromocytoma

Answer 43

benign enlargements of the medullary adrenal gland --> increases syn of catecholamine (uncontrolled)

Question 44

what are the symptoms of pheo

Answer 44

``` HA HTN palpitation tremor diaphoretic ```

Question 45

how do you diagnose pheo

Answer 45

find elevated VMA in teh urine