HPA axis, the adrenal cortex and steroid hormone synthesis Flashcards
suprarenal glands aka adrenal glands are located …
on top of the kidney
what two hormones are necessary for a full response in PC
CRH & AVP
Cortisol has two negative feedbacks in…
hypothalamic >. CRH & AVP
and AP (release of ACTH) cortcotropes
HPA
- CRH & AVP send neurons into Portal system
- Portal system sends secondary hormones into AP stimulating corticotropes to release ACTH
- ACTH is released and binds to ACTHR located in the cortex of the Adrenal gland
- releasing an increase of cortisol and adrenal androgens
- when you have enough cortisol it will start inhibiting CRH and AVP signaling and production of ACTH
Circadian rhythm
Daily rhythm
Adrenal anatomy
zona Glomerulosa
zona Fasciculata
Zona Reticularis
Cortex
80-90% derived from mesoderm (synthesis of steroid hormones) of abdominal wall
Medulla
10-20% derived from neuroectoderm (nervous system)
epinephrine & norepinephrine
zona glomerulosa
mineralocorticoids (aldosterone)
zona fasciculata
glucocorticoids (cortisol)
zona reticularis
DHEA
Adrenal regions have different sensitivity to ACTH
Zona fasciculata = hypertrophy and hyperplasia
zone reticularis = hypertrophy & hyperplasia
zona gomerulosa= no change
Where are MC2R expressed?
zona Fasciculata and reticularis
NOT MEEDULLA
When a stress activates CRH and AVP stimulating corticotropes in AP to release ACTH that binds to MC2R in the adrenal cortex …
What happens ??
increase of glucocorticoids (cortisol)
increase of DHEA
increase of adrenal weight (hypertrophy/hyperplasia)
increase in medullary hyperplasia (due to cortisol stimulation)
Hypertrophy
increase cell growth
Hyperplasia
increase cell number
Cholesterol
component of lipid bilayer
biosynthesis of acetyl CoA and acetoacetyl-CoA
Liver is main source of making cholesterol itself
brain contains the most»_space; myelin sheaths
Transports in blood (LDL - low density lipoprotein) – FA + hydroxyl group
CHO is synthesized by
cells «_space;can not supply all CHO for steroid production
CHO interacts with GPCR and ion pumps
BUT what if you don’t have any CHO??
without CHO ion pumps are deactivated
Steroidogenesis
synthesis of steroid hormones
main sites» adrenal cortex and gonads
Steroids hormones are products of …
a series of enzymatic rxns from a common precursor cholesterol
Cytochrome P450 Enzymes
oxidases with different functions + steroidogenesis
human genome 57 P450 enzyme genes
7 Mitochondrial
50 located in ER
P450scc
Located in Mito
CHO side chain is cleaved
p450c17
and p450c21
located in ER
adds -OH groups
P450aldo
located in Mito
biosynthesis of aldosterone
3beta-HSD
Dehydrogenase
Preg to Prog
17alphapreg-17 alpha prog
DHEA to Androstenedione
Sulfokinase
DHEA to DHEAS
Cortisol very widespread actions in the body… such as
- regulates a lot of different processes to maintain homeostasis
- a lot of different tissues express glucocorticoid receptors «_space;receptor for cortisol
What happens in response to Hypoglycemia
PVN»_space; CRH & AVP release into portal system
- stimulates corticotropes to release ACTH
- ACTH binds to MC2R in cortex of Adrenal gland
- increases cortisol which stimulates liver gluconeogenesis
- bring in more glucose into the blood
effects of cortisol
increases blood glucose by inhibiting uptake by tissues and by gluconeogenesis
- want to keep it in blood by
effects of insulin
decrease blood glucose increasing uptake by tissues
- want to remove it
how do cortisol keep glucose in the blood
muscle: stimulates catabolism to release AA myostatin (breaks down muscle cells)
Adipose tissues: stimulates lipolysis to release FA and glycerol»_space; activating HSL (hormone sensitive lipase)
peripheral tissues inhibits glucose uptake
SAVE GLUCOSE
Liver stimulates gluconeogenic enzymes PEPCK»_space; increasing blood glucose
