Adrenal (synthesis and regulation) Flashcards
principle source of cholesterol for steroidogenesis is what
circulating low-density lipoprotein (LDL)
how do LDLs enter steroidgenic cells
receptor mediated endocytosis
what happens to cholesterol in steroidgenic cells
either enters steroidgenic pathway or undergoes esterification to form cholesterol esters that coalesce into lipid droplets
what is the first step in steroid hormone synthesis
conversion of cholesterol to pregnenolone
rate limiting step in biosynthesis of steroids is what?
transfer of cholesterol to the inner mitochondrial membrane
what catalyzes the conversion of cholesterol to pregnenolone
P450scc
what facilitates the movement of cholesterol from outer mitochondrial membrane to the inner mitochondrial membrane
steroidogenic acute regulatory (StAR) protein
synthesis of StAR protein can be rapidly induced by what
a cAMP dependent mechanism
the flow of steroid hormone precursors form one cell compartment to the next after the formation of pregnegolone is what
unrestricted
Pregnegolone is used to synthesize what
all adrenal, gonadal, and placental steroids
specific synthetic products produced by a given steroidogenic tissue depends on what
which steroidgenic enzymes are expressed by that tissue
synthesis of what type of steroids can involve more than once cell type
steroid hormones
congenital deficiencies in steroidgenic enzymes can lead to what
deficiency in steroids past the block in the pathway
build up of intermediates ahead of the block in the pathway
when are steroid hormones released
as soon as they are synthesized
how are steroid hormones released
diffusion through plasma membrane
what provides a reservoir of precursor for steroid hormone synthesis
storage of cholesterol esters
what mobilizes stored cholesterol for steroidgenesis
tropic hormones
how do tropic hormones mobilize stores cholesterol
stimulate cholesterol esterase
inhibit acyltransferase activity
how is cholesterol converted to cholesterol esters
cholesterol acyltransferase in the ER
binding proteins able what for steroid hormones
higher concentrations in plasma then predicted by their limited solubility in aqueous solutions
protect from metabolization and excretion
provide plasma reservoir of steroid hormones
what are the steroid binding proteins (name them)
corticosteroid-binding globulin (CBG)
sex steroid-binding globulin (SHBG)
Vitamin D-binding globulin
corticosteroid-binding globulin (CBG) binds what
cortisol and progesterone
sex steroid-binding globulin (SHBG) binds what
estrogens and androgens
what affect plasma levels of binding proteins
disease
certain hormones
drugs
fraction of steroid pool binds non-specifically to what
albumin
what is the relation between free fraction of steroid hormones and that which is bound to binding proteins
in equilibrium with eachother
how are steroid hormones degraded
conversion to inactive metabolites
principle site of steroid inactivation is
liver
after inactivation what happens to steroid metabolites
conjugated to glucuronic acid or sulfate
conjugation of steroid hormone metabolites does what
facilitates clearance of inactive steroid hormones by:
increasing their solubility in water
decreasing affinity for binding proteins
what is a good clinical indicator of the function of the glands secreting the hormones
24-hour urinary excretion measurement
in certain peripheral tissues what happens to steroid hormones
converted to more active metabolite or a metabolite with a different action
steroid hormone receptors function as what
ligand-activated transcription factors
steroid hormone receptor has what type of signal
nuclear localization signal
nuclear localization signal (what does it do)
allows receptor to reside in the nucleus or be translocated to the nucleus when activated
when hormone binding site is unoccupied what do the receptors do
form large molecular weight complexes with chaperones proteins (heat-shock proteins)
what happens to chaperone proteins when steroid hormone binds its receptor
they dissociate
about DNA-binding domain of steroid hormone receptors is what and what is the result of that
highly conservative
receptors do not bind DNA unless the hormone is bound to its appropriate binding site on the receptor
steroid receptors will only bind DNA if
hormone is bound to its appropriate binding site on the receptor
hormone response element (HRE)
what is it
specific DNA sequences located in the promoter region of spefic genes
typical steroid hormone receptors do what when occupied
form homodimers
receptor homodimers form when?
two identical hormone-bound receptors bind to a given response element
allow hormone-occupied receptors recognize and bind target genes
hormone response element (HRE)
activation of gene transcription due to steroid hormones occurs when
the steroid hormone bound receptor dimers recruit a complex of coactivator proteins
in hormone-dependent negative regulation of gene transcription what happens
steroid hormone-bound receptor dimers recruit corepressor proteins to hormone binding site
binding of receptor antagonist does what to steroid hormone receptor
induces conformational change in the receptor that may prevent coactivators from binding to it
adrenal medulla (location and derivation)
located center of adrenal gland
derived from nuroectodermam cells
adrenal medulla is essentially what and secretes what
essentially modified sympathetic ganglion
catecholamines
adrenal cortex is derived from what
mesodermal cells
what are the layers of the adrenal cortex
zona glomerulosa
zona fasciculata
zona reticularis
all 3 zones of adrenal cortex can do what
synthesize pregnelone and progesterone from cholesterol
the conversion of cholesterol to 11-deoxycorticosterone (DOC) occurs via the same pathway where
zona glomerulosa
zona fasciculata
DOC is converted to aldosterone where
zona glomerulosa
what does the zona glomerulusa is the only zone to express what
aldosterone synthase
the zona glomerulosa does not express what
17alpha-hydroxalase activity of enzyme P450c17
b/c the zone glomerulosa does not express 17alpha-hydroxylase activity of enzyme P450c17 what cannot happen
neither cortisol nor androgens are formed in this zone
in the zona fasciculata formation of DOC is considered what type of pathway for this zone
minor pathway
DOC formed in the zona fasciculata is converted into what
corticosterone (a glucocorticoid)
what facilities the conversion of DOC to corticosterone in the zona fasciculata
11beta-hydroxylase
what is the principle glucocorticoid in humans
cortisol
what converts 11deoxycortisol to cortisol
11beta-hydroxylase
what is required for the synthesis of cortisol and androgens
17alpha-hydroxylase and 17,20-lyase activities
17alpha-hydroxylase and 17,20-lyase activities are associated with what enzyme
P450c17
P450c17 can be found where
zona fasciculata
zona reticularis
zona reticularis mainly synthesizes what
androgens
what enzyme is needed for formation of cortisol and androgens
P450c17
most glucocorticoids are synthesized where
zona fasciculata
transcription of StAR protein is induced by what
ACTH
Angiotensin II
transcription of StAR protein is induced by ACTH by what mechanism and where
via cAMP-dependent mechanisms
zona fasciculata and reticularis
transcription of StAR protein is induced by Ang-II by what mechanism and where
Ca2+-calmodulin-dependent mechanism
zona glomerulosa
Ang-II levels are elevated when?
renin-angiotensin system is activated by Renin due to low blood pressure
what induces aldosterone synthesis
K+
Ang-II
how does K+ activate aldosterone synthesis in zona glomerulosa
activation of VG-Ca2+ channels
what is the primary action of mineralocorticoids
maintain extracellular fluid volume by regulating Na+ resorption
mineralocorticoids promote exertion of what
K+ and H+
principle mineralocorticoids in humans
aldosterone
compare circulating levels of aldosterone, DOC, and cortisol in normal person
aldosterone and DOC are in similar quantities
cortisol 100x as much as aldosterone
what binding-globulin does aldosterone bind
corticosteroid-binding globulin (CSB)- weak affinity
does not have a specific aldosterone-binding globulin
most bound aldosterone is associated with what
albumin
why does cortisol not contribute to mineralocorticoid activity
converted to inactive cortisone in mineralocorticoid target tissues
what converts cortisol to cortisone
11beta-hydroxysteroid dehydrogenase (11beta-HSD2)
if 11beta-HSD2 is deficient or inhibited what can cortisol cause
mineralocorticoid hypertension
