Adrenal Physiology (5/16) Flashcards
List the parts of the adrenal gland from outside to in
- Capsule
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
- Adrenal Medulla
What does the zona glomerulosa make?
Aldosterone
What does the zona fasciculata make?
Glucocorticoids
What does the zona reticularis make?
Androgens
What does the adrenal medulla make?
Epinephrine
How are adrenocortical hormones made?
Synthesized form cholesterol by cytochrome P450 enzymes in the mitochondria and smooth ER of the adrenal gland
What is the rate limiting step in steroid production?
Side chain cleavage of cholesterol to pregnenolone by CYP11A1
Why is the glomerulosa cell the only location where glucocortiocids become mineralocortiocids?
Only cells with aldosterone synthetase enzyme
Aldosterone is released in response to…?
Increased
- angiotensin
- serum potassium
- ACTH (lesser stimulus)
Cortisol is released in response to…?
Increased
- ACTH
- Arginine vasopressin (lesser stimulus)
Androgens are released in response to…?
Increased ACTH
Norepi and epi are released in response to…?
Sympathetic nervous system activation and its synthesis is dependent on high local concentrations of cortisol
What does aldosterone regulate?
Binds mineralocortioid receptors to regulate blood volume and salt/water homeostasis
What does cortisol regulate?
Binds glucocorticoid receptor to regulate energy balance, CV, metabolic and immune homeostasis
What do androgens regulate?
Bind androgen receptor to regulate pubarche
What do norepi and epi regulate?
Bind adrenergic receptors to regulate CV effects and bronchial dilation
Renin is released in response to…?
Decreased afferent arteriole volume/low renal perfusion ie low blood volume coming into kidney (sensed via juxtaglomerular cells) and decreased distal tubule sodium concentration (sensed via macula densa)
Renin is decreased in response to…?
Increased afferent volume/high renal perfusion pressure and increased distal tubule sodium concentration (tubuloglomerular feedback)
What stimulates aldosterone release?
K+ and angiotensin II stimulate aldosterone synthetase in the zona glomerulosa. ACTH can also stimulate aldosterone synthetase (to a lesser extent).
Aldosterone regulates extracellular volume and potassium balance.
What makes/releases renin?
Juxtaglomerular cells. Renin then converts angiotensinogen to angiotensin I which is converted to angiotensin II by ACE. Angiotensin II then stimulates aldosterone release
Where does aldosterone work and how?
In the distal cortical collecting duct principal cells. Binds mineralocortioid receptors which leads to inc transcription of Na/K channels bringing more Na into the blood and more K+ out…water follows Na.
What causes CRH to be released?
CRH is released in a circadian rhythm. Also physical stressors like hypoglycemia, hypotension, surgery, fever, injury
What cell types does CRH stimulate?
Corticotrophs
What stimulates ACTH release?
CRH, vasopression, pro-inflammatory cytokines (inflammation)
What is the negative feedback in cortisol axis?
Cortisol has neg feedback on ACTH and CRH
What protein is cleaved to make ACTH?
POMC is post-translationally cleaved to become melanocyte stimulating hormones, beta endorphin, beta lipotropin and ACTH
What is the ACTH specific receptor?
Melanocortin 2 receptor on adrenal tissue. It increases LDL receptors to bring in more cholesterol as a precursor for steroid hormones and activates CYP11A1 enzyme for cholesterol side chain cleavage.
How else can ACTH fxn?
Can fxn as melanocortin, activating the melanocortin 1 receptor expressed on melanocytes
Describe cortisol and ACTH secretion rhythms
Diurnal Cortisol Secretion
ACTH and cortisol are pulsatile throughout the day and follow a circadian rhythm
When is cortisol highest?
6-8 hours after sleeping, begins to decline after awakening
When is cortisol lowest?
Midnight
What are cortisols actions on the liver?
Gluconeogenesis, decrease glucose uptake
What are cortisols actions on skeletal muscle?
Release of AAs
Blocks insulin dep glucose uptake (insulin resistance)
What are cortisols actions on inflammatory and immune cells?
Potent immunosuppressant and anti-inflammatory effects
- dec macrophage
- dec T cell
- dec mast cell degranulation
What are cortisols actions on peripheral adipose tissue?
Release of free fatty acids and glycerol
What are cortisols actions on the heart?
Inc BP via vasoconstriction
Inc adrenergic receptor responsiveness
What are cortisols actions on bone?
Inc osteoclast activity, dec calcium absorption
What are cortisols actions on vascular smooth muscle
Vasomotor tone
Responsiveness to vasoconstrictors
–>inc BP
What are cortisols actions on the adrenal medulla?
Epinephrine synthesis (activates PNMT enzyme)
What is the cortisone shunt?
The mineralocorticoid receptor has higher affinity for cortisol than aldosterone. Aldosterone sensitive tissues (like the kidney) have 11-beta HSD2 enzyme shunt that makes cortisol, cortisone. In the tissues where you need more cortisol, like the liver, 11-beta HSD1 will make cortisone into cortisol
What does licorice do?
Prevents inactivation of cortisol by inhibiting 11betaHSD2. Leads to activation of MCR by cortisol and therefore hypertension and hypokalemia (a pseudohyperaldosteronism)
What are the adrenal androgens?
DHEA, DHEAS, androstenedione
When is there a natural inc in production of adrenal androgens?
With age
What is androstenedione converted to?
Testosterone and estrone in peripheral tissues
Where does medulla receive input from?
Sympathetic nervous system through pregang fibers from thoracic spinal cord
What are medulla cells like
Nerve gang, but lack synapses from postgang fibers and releases secretions directly into blood
What is the RLS in catecholamine synthesis?
Tyrosine enters chromaffin cells and is converted by tyrosine hydroxylase to dopa, which is the RLS in catecholamine synthesis
How does cortisol promote epinephrine synthesis in medulla?
Upregulates PNMT, enzyme that converts norepi to epi
What % epi and norpei does medulla secrete?
20% norepi, 80% epi
What can catecholamines be converted to after norepi and epi?
Metanephrines (normetanephrine and metanephrine)
What is the short life of metanephrines and catecholamines?
Short! So they signal through 2nd messenger systems in teh cell
What receptors do catecholamines bind?
Adrenergic receptors
Alpha1 (fxn, location, 2nd messenger)
Fxn: Adrenergic receptor leads to vasoconstriction and inc peripheral resistance
Location: Arterial/venous vasculature
2nd messenger: Inc IP3
Alpha 2 (fxn, location, 2nd messenger)
Fxn: Inhibits insulin release
Location: arterial/venous vasculature, nerve terminals
2nd messenger: Dec cAMP
Beta 1 (fxn, location, 2nd messenger)
Fxn: Tachycardia, inc myocardial contractility, inc release of renin
Loc: Heart, juxtaglomerular apparatus
2nd m: inc cAMP
Beta 2 (fxn, location, 2nd messenger)
Fxn: Vasodilation, bronchodilation
Loc: Heart, skeletal muscle, vasculature, bronchial smooth muscle
2nd m: inc cAMP
Look at summary slides
Look at summary slides
