Biochem 3: Adrenals Flashcards
cholesterol derivative hormones are what type of hormones
steroid hormones
in which part of the adrenals are steroid hormones made
the cortex
Which hormones are created where in the adrenal cortex?
Zona glomerulosa: mineralocorticoids (aldosterone)
Zona fasciculata: glucocorticoids (cortisol)
Zona reticularis: androgens (DHEA
What type of hormones are located in the medulla, name the 3 hormones too?
catecholamines from tyrosine
NE, Epi, Dopamine
Explain how ACTH is important in synthesis of adrenal cortex hormones
Starts the cascade effect of hormone production when ACTH (released from AP) acts on the Gs (cAMP) receptor
What is the cascade effect in synthesis of adrenal cortex hormones
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
what are steroid carrying proteins
proteins that are important in transporting steroid hormones to distant sites
why are steroid carrying proteins so important
steroid hormones are hydrophobic and so they must be attached to a protein
GIve an example of steroid carrying proteins
Cortisol binding protein/globulin
it carries:
1.cortisol
2. aldosterone
CBP is produced in the adrenals TRUE or FALSE
FALSE; they are produced in the liver
whats the point of cortisol-cortisone shunt
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
What happens when cortisol binds with MR
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
what 2 hormones can bind to MR
cortisol and aldosterone
So how does the shunt prevent cortisol from binding with MR
converts cortisol into cortisone
cortisone can’t bind with MR receptor.
what 2 enzymes are involved in activating and inactivating cortisol
11B-HSD2 - inactivator of cortisol in the KIDNEY (cortisol–> cortisone)
11B-HSD1 - activator of cortisol in the LIVER (cortisone–>cortisol)
what is so special about the skin
has 11B-HSD1; allows cortisone cream to convert to cortisol (active form)
Thats why topical is effective
What is interesting about licorice
contains glycyrrhizic acid which INHIBITS 11B-HSD2.
this allows cortisol access to MR which leads to HTN and hypokalemia
What is the role of CYP450 in steroid hormones
convert free cholesterol to metabolite pregnenolone
Pregnenolone is needed …
for the production of all steroids: mineralocorticoids, glucocorticoids, androgens
which enzyme catalyzes cortisol and androgen
CYP17
which hormones do CYP21 catalzye
cortisol and mineralocorticoids
TRUE or FALSE; if theres a deficiency in one of the enzymes it will shift production of steroids to the other pathway
TRUE
if CYP21 is deficient –> coritsol and mineralocorticoid isn’t produced but since CYP17 still works androgen will be produced
TRUE or FALSE; cortisol needs either pathway to work in order to be produced
FALSE; it needs the activity of BOTH CYP17, 21 (and 11)
what is Cushing Syndrome
excess cortisol for any reason
what is Cushing Disease
limited to pituitary adenoma –> increased ACTH levels
Cushing Syndrome can be classified on LOCATION OF PRODUCTION
Endogenous: w/in the hypothal, pit, or adrenal axis
Exogenous: source outside the body (DRUGS)
Cushing Syndrome can be classified on LOCATION OF LESION
Primary: abnl in the ADRENAL gland –> increased cortisol prodcution
Secondary: abnl in the PITUITARY gland –> increased cortisol level
- typically by increasing ACTH levels
What are the 4 symptoms of Cushing Syndrom
- HTN
- Weight gain
- Wound
- Muscle wasting
What is Addison Disease
progressive destruction of adrenal gland —> decreasing steroid synthesis
What will you see with the hormone levels
LOW cortisol and aldosterone
What are the symptoms of Addison Disease
Hyperpigmentation
Hyponatremia
Hyperkalemia
Explain how hyperpigmentation arises in Addison
low cortisol levels –> increase ACTH levels
ACTH release is associated with increases in MSH –> increased MSH –> hyperpigmentation
which hormone is responsible for hyponatremia and hyperkalemia in Addison
Low Aldosterone
What is congenital adrenal hyperplasia
a block in corticosteroid synthesis bc of defect in CYP21 –> leading to shunting into ANDROGEN (CPY17)
increased androgen
what are the symptoms of CAH
virilization in females –> too many androgens (ambiguous genitalia)
hyperkalemia, hyponatremia, and wegith loss –> NO ALDOSTERONE –> salt and water loss
what is apparent mineralocorticoid excess (AME)
cortisol binds to MR –>mimics high ALdosterone levels –> hypokalemia, hypernatremia –> HTN
which enzyme is defective in AME
11B-HSD2 in the kidney (cortisol –> cortisone)
How are catecholamines synthesized
phenylalanine –> L-Tyrosine –> Dopa –> Dopamine –> NE –> Epi
TRUE or FALSE: neurons make both NE and Epi
FALSE; neurons make up to NE and ADRENAL MEDULLA makes Epi
what 2 enzymes metabolize catecholamines
MAO (monoamine oxidase)
COMT (cathechol -O-methyl transferase)
what do the catecholamine eventually break down to
vanillylmandelic acid, VMA
aka 3-methoxy-4-hydroxymandelic acid
where can you find VMA
excreted in the urine and also seen in teh blood
what is pheochromocytoma
benign enlargements of the medullary adrenal gland –> increases syn of catecholamine (uncontrolled)
what are the symptoms of pheo
HA HTN palpitation tremor diaphoretic
how do you diagnose pheo
find elevated VMA in teh urine
