Physiology: Endocrine # 10 - Adrenal Cortex Hormones.

Front 1

adrenal cortex - what are its layers and what are the major products of each layer?

Back 1

zona glomerulosa : makes aldosterone (mineral corticoid steroid hormone)

zona fasiculata: makes glucocorticoids (mainly cortisol - required for life).

zona reticularis: makes DHEA-S (DiHydroEpiAndrosterone sulfate) and Androstenedione. These are precursors to androgens/estrogens.

Front 2

what are the primary outputs of the cortex and what's most active?

Back 2

primary outputs are cortisol and DHEA-S, though the tiny amount of aldosterone that's made is more active than the androgen precursors.

Front 3

where does the MEDULLA come from? what are the cell types called?

Back 3

neuroectodermal cells of the sympathetic ganglia.

cells = chromafin cells.

Front 4

what are the main outputs of the medulla? In what percentages are they made? why?

Back 4

main outputs are norepi and epi.

note that epi makes up >80% because most of the blood bathing the medulla passes through the cortex first, bringing with it lots of glucocorticoids.

these activate PNMT (phenylethanolamine n methyl transferase) which converts norepi to epinephrine.

just think that the adrenals are known for releasing epinephrine - that's how you remember the percentages.

Front 5

how are steroid hormones stored in the cortex?

Back 5

there is no storage of steroid hormones - they're made and released.

Front 6

on which regions of the cortex does ACTH work?

Back 6

mostly on the fasiculata to release cortisol, but also on the reticularis to release its hormones (glucocorticoids also made in the reticularis).

Ang II is what makes aldosterone leave the glomerulosa.

Front 7

what's the rate-limiting step in steroid biosynthesis?

Back 7

availability of cholesterol from lipid droplets in the cell to the p450 desmolase enzyme in the mitochondria.

Front 8

what do the p450 enzymes do, generally? as in what kinds of reactions? what cofactors are required?

Back 8

steroid hydroxylations.

requires lots of 02, NADPH, flavoprotein, and ANDRENOXIN (contains iron)

Front 9

what happens if one cortical steroid biosynthetic pathway gets blocked? use cortisol as an example:

Back 9

if you block the production of cortisol, there will be more precursors around to make other things.

additionally, the lack of cortisol will stop negative feedback of ACTH, making levels of ACTH go way up - this will upregulate the release of other steroid hormones (androgen/estrogen precursors, etc). DHEA-S up.

Front 10

How many carbons does cortisol have?

Generally, what group is added/taken away from cholesterol to make cortisol?

What is the rate limiting step in its creation and what controls this step?

Back 10

Cortisol has 21 carbons, just like progesterone and aldosterone.

Cortisol comes from hydroxylation, aka the addition of a carbon 11 hydroxyl.

It's first step is the rate-limiting...conversion of cholesterol to PREGNENOLONE via P-450 desmolase, aka cholsterol desmolase.

pregnenalone is the precursor for pretty much all our steroid hormones including aldosterone, DHEA, cortisol.

Front 11

aldostrone synthesis - how many carbons are there and where is the OH added?

what common precursor(s) do cortisol and aldosteorne share?

Back 11

aldosterone also has 21 carbons like cortisol.

here though, the hydroxyl is added at the 18 position carbon.

note that pretty much the same enzyme that does the 11 hydroxylation in cortisol does the 18 hydroxylation in aldosterone...not sure why it does it in a different place here.

both share, of course, pregnanalone as a precursor, as well as progesterone (not required for cortisol, is required for aldosterone).

Front 12

men vs. women - how important are the androgen precursors in the adrenals?

how many carbons do sex steroids have? where are they hydroxylated?

Back 12

in women they provide 50% of the androgens required. in men, not so important.

androgens and estrogens are hydroxylated at the 17 position.

so, cortisol = 11, alsoterone = 18, and sex = 17

Front 13

what happens to DHEA-S, DHEA, and androstendione?

Back 13

they're converted to testosterone and estradiol by peripheral tissues. by themselves, they're weak androgens.

Front 14

what does cortisol feed back on?

Back 14

it rapidly stops the effect of CRH on the pituitary (blocking receptors?) to stop ACTH release.

also can downregulate ACTH secretion

Also can downregulate CRH secretion - so all of these stop more


NOTE - there's a synthetic analog called DEXAMETHASONE that can do the same thing.

Front 15

what does cortisol do and when is it released? how is it in relation to insulin? how does hypoglycemia affect it?

Back 15

of course released by ACTH, but this can be overridden by stress inputs.

its required for survival of stressed animals. released during exercise.

immune activation can turn it on (probably so it'll feedback and shut itself off?)

it'll try to produce glucose from proteins (biggest effect) while simultaneously encourage storage of that new glucose as GLYCOGEN (not gluconeogenesis for immediate release).

It's a big antagonist of insulin, stopping its action to intake glucose into muscle cells.

it's a big promoter of glucagon - encouraging breakdown (cortisol is big time turned on by hypoglycemia) and helps rebuild the glycogen stores after they've been used up.

so it's catabolic, anabolic, and DIABETOGENIC (opposes insulin)

Front 16

if cortisol increases glycogen production, why release it if you're hypoglycemic?

what does it do to bone/CT?

Back 16

it makes tissues less sensitive to insulin, so you can keep your blood glucose high.

it simultaneously gets protein turned into sugar turned into glycogen to get ready to release it if needed.

it reduces bone and CT production.

Front 17

what's cushing's syndrome?

Back 17

too much cortisol.
NOTE: cortisol is upped during hypoglygemia, sepsis, after surgery, major fracture.

people tend to gain weight (makes you eat more - get more CUSHion).

skin becomes thin (ct goes down) and capillaries rupture = bruising.

get muscle weakness and atrophy and osteoperosis.

Front 18

what hormones can be messed up in the cortisol pathway and what can this cause?

Back 18

beta 21 or beta 11 hydroxylase are used in the synthesis of both cortisol and aldosterone.

this makes a lot more available for the production of adrenal cortical androgens, which can cause fetal masculinization.

Front 19

what are the major functions of aldosterone?

through what second messenger does AngII act to cause aldoserone secretion?

what inhibits aldosterone release, maybe?

Back 19

maintain fluid volume and retain sodium. also, to get rid of excess potassium through the kidneys.

Stimulated by Ang II via IP3/Ca++ acting on AT1 receptors.

ANP and BNP can stop aldosterone release.

Front 20

talk about adrenal cortex hormones in post-menopausal women. what's the main estrogen?

Back 20

the secreted sex hormones by the zona reticularis become the dominant source of estrogen/testosterone after the ovaries dry up.

andrenostendione becomes estrone and testosterone (testosterone can become estradiol) - the ESTRONE becomes the major estrogen in postemenopausal women.

Front 21

what are the signs of addison's disease?

Back 21

first loose cortical androgen production, so loose some hair (especially in women)

also get high ACTH from lack of feedback inhibition.

Hypoglycemia.

WEIGHT LOSS, FATIGUE.

Hyperpigmentation (all that ACTH getting pumped out comes from POMC which also contains the MSH fragment, where the M stands for melanocyte)

low blood pressure.

HYPERKALEMIA from lack of aldosterone...can also cause metabolic acidosis.

Front 22

cushing's disease?

Back 22

overproduction of ACTH, so get too much cortisol release. weight gain. high cortisol and androgen levels.

hypERglycemia (diabetes).

muscle wasting.

bad wound healing

virilization of women.

hypertension (aldosterone up).

osteoperosis