what's basically the hormones the adrenal cortex makes?

what about the medulla?

cortex - steroid hormones incl. gluco/mineralocorticoids

medulla - catecholamines

what specific hormones do the three layers of the adrenal cortex produce?

which hormones do the medulla produce?

cortex: zona glomerulosa - aldosterone

  zona fasciculata, reticularis - cortisol & androgens

the deeper you go the sweeter:

G-salt, F-sugar, R-sex

medulla: epi/norepinephrine 

what's the precursor to catecholamines?

what's the rate limiting enzyme?

what enzyme converts NE to E?

where does this conversion occur?

tyrosine

tyrosine hydroxylase (tyrosine to DOPA)

PNMT

in chromaffin cells

what stimulates synthesis of catecholamines?

what causes neg feedback? on what enzyme?

sympathetic stimulus

dopamine & NE neg feedback on tyrosine hydroxylase

α1 receptors

distribution?

what do they activate?

which has a more potent effect, NE or E?

what effect on arteries, intestines, iris, bladder sphincter, liver, pancreas, skin

wide distribution in body

activate Gq-PLC-intracellular Ca²⁺ second messenger pathway

NE is a more potent activator

vasoconstriction

intestinal relaxation

iris dilations

bladder sphincter contraction

glycogenolysis

inhibit insulin release

skin sweating

function of α2 receptors?

where are they found in the body?

order of potency of NE & E?

inhibit NE release

mostly in presynaptic terminals

NE more potent than E

β1-3 adrenergic receptors

what effect in the cell?

order of potency of NE & Epi?

where found in the body?

activate Gs/AC/cyclic AMP second messenger cascade

affect of β1 receptors

β1: cardio acceleration 

cardiac contractility go up

lipolysis

vasodilation

bronchodilation

uterine relaxation

increase glyconeogenesis

lowers glucose utilization

stimulated: more Epi released

basal: more NE in blood (maintains sympathetic tone like BP control)

which enzymes break down the catecholamines?

how does the body get rid of them?

what are MAO inhibitors used for?

MAO & COMT

excreted in urine

MAO inhibitors used to treat depression

pheochromocytoma

what causes it?

symptoms?

catacholamine secreting tumor in the chromaffin cells of adrenal medulla

symptoms - 5 p's

pressure (BP)

pain (headache)

perspiration

palpitations

pallor

what's the precursor to steroid hormones?

what's the rate limiting step?

cholesterol

conversion of it to pregnenolone

major - cortisol & aldosterone

minor - DHEA & androgens

what steroid hormone is produced in each layer of the adrenal cortex? 

and what control mechanism is each involved in?

zona glomerulosa - aldosterone - renin-angiotensin system

fasciculata - cortisol - ACTH

reticularis - androgens - ACTH

how much cortisol is free in the blood? 

what is the rest mostly bound to?

10% free

the rest is bound to CBG (corticosteroid binding globulin)

how much aldosterone is free in the blood?

what is the rest mostly bound to?

40% free

the rest is bound to Albumin

they are metabolically inactivated in the liver & excreted in the urine

water solubility is increased by conjugation with other compounds in the liver

what's the main function of glucocorticoids?

what about mineralocorticoids?

is there overlap?

gluco - intermediary metabolism

mineral - electrolyte metabolism

there's overlap, example, aldosterone has a minor glucocorticoid function and visa versa for cortisol

thus if one is out the other can compensate a tiny bit

1. stimulation of gluconeogenesis & glycogensis

2. increased protein catabolism

3. increased lipolysis

blocks inflammation

supresses the immune system

stimulates gluconeogenesis

function of aldosterone?

how does it achieve this?

what are the non-renal targets?

increase BP by increasing blood volume

regulate renal tubule to excrete K & retain Na

does this by increasing activity & expression of lumenal Na channels

non-renal targets: sweat glands, salivary glands, colon, heart

what 2 things does ACTH do in the kidney?

what 3 physiological effects regulate ACTH release?

adrenocortical growth & glucocorticoid secretion

1. stress

2. circadian rhythm (just before rising in the morning)

3. cortisol exert neg feedback on hypothalamus (CRF release) & ant pituitary (ACTH release)

LDL uptake -> converted and stored as cholesterol esters

ACTH then cause it's uptake into the mitochondria

it's converted to pregnolone ---> cortisol

what effect does exogenous glucocorticoids have on the adrenal cortex?

what danger is involved?

it supresses the hyptohalamic-pituitary-adrenal cortex synthesis of cortisol

eventually atrophy of the adrenal cortex

dangerous to suddenly withdraw it

regulated by electrolyte balance (K vs. Na)

and by the renin-angiotensin system (RAS)

angiotensin II causes aldo release.

Addison's disease

what's the main problem?

caused by what?

symptoms?

what's and Addisonian crisis?

Adrenal Atrophy Absence of hormone production

adrenal cortex can't synthesize cortisol & aldosterone

symptoms are

impaired intermediary metabolism & weight loss

reduced tolerance to stress

hyperpigmentation (cross reaction of excess ACTH & MSH)

hyperkalemia &or hyponatremia

Addisonian Crisis: life threatening state resulting from inability to cope w/ stress

secondary adrenocortical insufficiency

cause?

what's different than primary insufficiency / addisons disease?

symptoms?

pituitary can't synth ACTH

aldosterone system still intact

symptoms similar to primary but less severe,

no hyperpigmentation

cushing's syndrome

main effect?

4 causes?

adrenal cortical hyperfunction

excess glucocorticoid & aldosterone

can be caused by

2^o adrenal tumor (low ACTH)

1^o pituitary tumor - excess ACTH (ACTH dependent)

3^o hypothalamic dysfunction - excess CRF

ectopic (high) ACTH-secreting tumor (common in lung carcinoma)

symptom of cushing's syndrome

how can one diagnose this syndrome?

centripetal obesity

hypertension

hyperglycemia

hirsutism (hairy face)

moon face

Dx - dexamethasone suppression test (inhibits ACTH release)

healthy - low cortisol after low doe

ACTH-producing pituitary tumor - high cortisol after low dose, low cortisol after high dose

Ectopic ACTH producing tumor - high cortisol after high/low dose

what's 1^o and 2^o hyperaldosteronism?

what are the effects of it?

1 - adrenal tumor that causes excess mineralocorticoids (aldosterone) - hypertension

2 - excessive renin-angiotensin activity

so the difference is if renin is high or low

hypokalemia & hypernatremia

water retention leads to edema, ECF expansion

CAH (congenital adrenal hyperplasia)

21-hydroxylase deficiency

low cortisol & mineralocorticoids

hypotension - hyperkalemia

CAH (congenital adrenal hyperplasia)

low sex hormones, low cortisol, high mineralocorticoids

hypertension - hypokalemia

phenotypically female but no maturation

CAH (congenital adrenal hyperplasia)

low cortisol & aldosterone

high sex hormones

masculinization

hypertension