8 Cortisol Flashcards
list the layers of the adrenal gland
capsule, zona glomerulosa, zona fasciculata, zona reticularis, adrenal medulla
which layer of the adrenal gland is the largest?
cortex (90%)
what is the precursor to the hormones produced in the adrenal gland?
cholesterol
are the zones of the adrenal gland able to produce the same hormones?
no, the don’t express the same enzymatic machinery
what is the first step of steroidogenesis?
conversion of cholesterol to pregnenolone in the mitochondria.
what is the enzyme called that helps shuttle cholesterol from storage into the mitochondria?
StAR (Steroid Acute Regulatory Protein)
what are the hormones that can induce cAMP? significance?
any protein capable of binding to GPCRs; can lead to StAR expression, thus leading to steroidogenesis
where are the cells located that produce cortisol?
zona fasciculata (middle of cortex)
is cortisol stored?
no - it’s a steroid (fat soluble) hormone so it’s not stored; it is produced only when necessary
half-life of cortisol?
70-120 mins
how is cortisol regulated?
converted to inactive cortisone in the liver and excreted in the urine; cortisone can be reactivated by other cell types
functions of cortisol?
depends on cell type, eliciting different cellular responses
- affects liver by stimulating glycogen synthesis
- stimulates gluconeogenesis
- increases FA production (similar to diabetic symptoms)
- anti-inflammatory
negative effects of cortisol?
too high concentrations can lead to depression and psychosis, and GI tract uclerations
prolonged exposure can lead to skin thinning or reduced muscle mass
can negatively impact vertical growth
what enzyme is required for the conversion of cortisol to cortisone?
11B-HSD type 2
the B is a beta
why is the inactivation of cortisol to cortisone important?
cortisol can also interact with aldosterone receptors, which means cells needs to be able to negotiate that. cortisol is also produced at a much higher concentration in compared to aldosterone (the cortex layers is larger).
Aldosterone responsive cells need to nerf cortisol so they can do their main job
what happens when you’re deficient with HSD11B2?
you get excess cortisol: interacts with MR (mineralocorticoid receptor) elicits aldosterone-like responses in the cells, called AME (apparent mineralocorticoid excess)
what enzyme does the skin have that affects cortisol?
HSD11B1 - inactivates active form
how does cortisol function?
cortisol, being a steroid, is received by a nuclear receptor called GR (glucocorticoid receptor) - in its inactive form, they’re present in the cytoplasm, not the nucleus. when bound - it can dimerize with another activated GR which an shuttle into the nucleus where the dimer of GR can act as a transcription factor
what kind of transcription factor does cortisol act as?
depends on cell type
- muscle cells/adipocytes: increased catabolism
- liver: increased glycogen synthesis and increased gluconeogenesis
compare/contrast cortisol and insulin
they’re basically opposites. overall with cortisol, there is increased glucose in the blood while there is increased glycogen storage in the liver
how does cortisol have anti-inflammatory function
inhibits this response by immune cells; can be used to treat rheumatoid arthritis; can cause atrophy in immune tissues by stimulated apoptosis (lymph nodes)
reduces number of immune cells able to synthesize antibodies
concerns with taking cortisol for medication?
- inducing of diabetic-like symptoms
- increased risk of infection
- advised not to take long-term
list some other effects of cortisol that pertains more to circulation and nervous system
- sensitizes arterioles to action of norepinephrine (hypertension)
- leads to glycogenolysis, leading to hyperglycemia
- known to have positive effect on the CNS, something also known as the euphoric steroid
- interacts with MR, leading to increased fluid in circulation (hypervolemia —> hypertension)
what hormone primarily regulates cortisol?
ACTH
is cortisol capable of negative feedback?
yes, at both hypothalamic and pituitary levels
does cortisol have diurnal rhythm?
yes, because ACTH also does. ACTH concentrations are highest in early morning, which means cortisol’s peak is also during the early morning
True or false: release of cortisol is pulsatory
true
true or false: increased production/release of cortisol is due to increased amplitude, not frequency
false - it’s due to increased frequency
what stimulus is capable of increasing cortisol production?
stress
true false: cortisol must be transported with a binding protein
true; most of it (75%) is transported with CBG; serum albumin can also be bound to cortisol (15%); the rest is free (10%)
what is CBG?
Cortisol Binding Globulin: binding protein for cortisol
where is CBG synthesized?
in the liver
is bound or free cortisol activated or inactivated by the liver?
free - CBG protects cortisol from being destroyed by already being more water soluble
it is inactivated (cortisone) by making it more water soluble to be excreted by the kidney
what happens when there’s too much cortisol? (blood sugar, muscles, skin, immune, blood pressure)
Cushing’s syndrome
- diabetes mellitus (bc of induced hyperglycemia)
- muscle wasting (bc catabolism of gluconeogenesis)
- thinning of skin
- thinning of bones: osteoporosis
- susceptibility to infection
- hypertension (bc regulation of permeability of arterioles from acting like aldosterone)
- production of tumors (can be functional or not; can further increase cortisol production)
if a tumor is at the level of the adrenal gland, is production of cortisol reliant on ACTH?
no, because these cells are already capable of producing cortisol without ACTH
what is Iatrogenic?
illness caused by the doctor :(
what is the sella turcica?
saddle shaped bone that houses the pituitary gland. it can be enlarged due to Cushing’s syndrome
what does Cushing’s syndrome do to the back?
can cause a buffalo hump
what happens when there is too little cortisol?
Addison’s disease
- most often caused by autoimmunity
- fatigue, weakness, faintness, nausea, vomiting, low blood pressure, salt craving, severe pain in muscles and joints, excessive freckling
describe the Addison Crisis Pathway
when there is hypofunction of adrenal gland leading to low levels of cortisol, this can lead to defects in liver functions (low concentration of sugar in blood); low levels of cortisol can also reduce enzymes in the GI tract leading to decreased blood sugar. this all affects the brain’s function because of its limited fuel.
treatment must tailor to this cycle; requires continuous monitoring
