lectures - adrenal cortex + steroids

what are the main types of adrenal steroids

glucocorticoids (GCs)

Mineralocorticoids (MCs)

Adrenal androgens

what are some examples of GCs

cortisol and corticosterone

what animals have cortisol

fish/larval amphibians

most mammals

what animals have corticosterone

rodents

birds

reptiles

adult amphibians

what do GCs generally do

regulate metabolic fuel availability

what is an example of a MC

aldosterone

what do MCs generally do

play important role in water + salt balance

C19s are

androgens

C18s are

estrogens

MCs have a keto group at

C18

why is C17 important in adrenal androgens

its where the SC attaches to

what is the main product of the adrenal cortex

cortisol

describe the general process of HPA axis

CRH from hypothala → ACTH from ant pit → cortisol + others from adrenal cortex → cortisol (-) feedback to ant pit + hypothala

does cortisol require a carrier to move through blood

yes

Define secretagogue

substance that causes the secretion of another substance

what is the pattern of cortisol synth and release

on circadian rhythm with timed surge to overcome (-) feedback

without cortisol what happens to CRH and ACTH levels

they go wild as there is not regulation from cortisol

in an animal with an adrenalexctomy, what can be used to keep ACTH and CRH levels low

DEX - synthetic GC that can act like cortisol in (-) feedback

what mouse is a model for AVP deficiency

brattleborro lab rat (BB)

what do BB lab rats show

that without AVP, ACTH release in response to hypoglycemia is dampened

describe the adrenal cortex

derived from mesoderm of abdominal wall

80-90% of adrenal gland mass

made up of 3 zones

what are the 3 zones of the adrenal cortex

zona glomerulosa - outer most

zona fasciculata

zona reticularis - inner most

what is made in the zona glomerulosa (ZG)

MCs like aldosterone

what is made in the zona fasciculata (ZF)

GCs like cortisol

what is made in the zona reticularis (ZR)

androgens like DHEA

describe the adrenal medulla

derived from neuroectoderm

makes up 10-20% of adrenal gland mass

part of autonomic/sympathetic NS

what kind of hormones are made in the adrenal medulla

epi and norepi

epi and norepi are derivatives of

tyrosine

do epi and norepi require mem receptors

yes

how does the ZF respond to ACTH

hypertrophy and hyperplasia

how does ZR respond to ACTH

hypertrophy and hyperplasia

how does ZG respond to ACTH

virtually no change

in general, ACTH acts on the adrenal cortex to....

↑ GCs

↑ DHEA

↑ adrenal weight

↑ medullary hyperplasia

what is the ACTH receptor

MC2R which is expressed in ZF and ZR

is MC2R expressed in adrenal medulla

no

describe MC2R

GPCR using Gs

statins inhibit what

HMG-CoA reductase therefore inhibiting cholesterol synth

cholesterol is a derivative of

acetyl-CoA

what is the function of cholesterol (CHO)

maintain fluidity of plasma mems

what makes up CHO

acetyl-CoA + acetoacetyl-CoA

what is the main source of de novo CHO synth

liver

what contains most of the bodys CHO

the brain in the form of myelin sheaths

how does CHO transport in blood

on LDLs

describe an LDL

CHO bound to long chain FA at hydroxyl group

CHO is the substrate or precursor for....

all steroid hormones and is critical component for cell mem

can cells synth all needed CHO

no cells cannot supply all CHO needed for steroid production so we still need some in diet

CHO in plasma mem interacts with what

GPCR and ion pumps which have specific binding site for CHO molcs

if CHO is missing from plasma mem, ion pumps are deactivated

define steroidogenesis

synth of steroid hormones

where are the main sites for steroidogenesis

adrenal cortex and gonads

some made in brain and placenta

steroid hormones are a product of...

enzymatic rxns starting from CHO

in steroidgenic cells, where in particular are steroids made

starts and ends in the mito, intermediate steps in ER

are steroids stored

no

what converts CHO to pregnenolone

P450scc, it removes SC from cholesterol

when converting from pregnenolone to an androgen, what is removed

C20 + C21 are removed to make the C19 androgen

aldosterone is made in the

ZG

cortisol and corticosterone are made in the

ZF

aldosterone synthase is restricted to

ZG

17α-hydroxylase is not expressed in

ZG

17,20 lyase activity of CYP17A1 is only in

ZR resulting in DHEA synth

what happens when LDL binds

LDL + receptor gets endocytosed, LDL is hydrolyzed by CHO esterase

LDLrs are moved back to mem

what does PKAs role in steroidogenesis

phoses stAR and P450scc

what does PKA do to stAR

phoses stAR to grab free CHO in cyto and moves it to mito

what is the 1st rate limiting step of steroidogenesis

stAR

describe cytochrome P450 enzymes

family of oxidases with diff functions including steroidogenesis

7 in mito

50 in ER

where is P450scc found and what is its function

in mito, CHO SC cleavage

where is P450aldo found and what is its function

MIT, biosynth of aldosterone