Adrenocortical Hormones Flashcards
What type of hormone is cortisol?
Steroid Hormone
Where is cortisol produced?
Adrenal Gland (Zona Fasciculata)
Cortisol is an example of a …
… glucocorticoid/corticosteroid
Glucose Metabolism
Cortisol production is dependent on …
… adrenocorticotropic hormone (ACTH)
What are the steps of cortisol production?
Synthesis of cholesterol
Mitochondrial Conversion
Smooth ER
Which receptors does cortisol bind to?
Glucocorticoid Receptors (GRs)
Most cells have a GR
How is cortisol transported?
90% bound to corticosteroid-binding globulin (CBG)
3% free in the plasma
Another name for cortisol bound to CBG is …
… transcortin
Which cortisol can enter the cell?
Free cortisol
In which condition does total cortisol and CBG increase?
During pregnancy
Note free cortisol does not increase. The patient shouldn’t show signs of high cortisol
What are the effects of cortisol?
Glucose and overall metabolism
Immune system
Cognition
Bone formation
Fetal Development
What are the metabolic effects of cortisol?
Increases energy-generating substances
What are some energy-generating substances which cortisol can generate?
Glucose
Glycerol
Amino-acids
How does cortisol increase serum glucose?
Increases Gluconeogenesis
Decreases Glycogen Formation
Reduces Glucose Uptake
Decreases Insulin Secretion
Increases Glucagon Secretion
How is glycerol generated?
Increased lipolysis
How are amino acids generated?
Increased proteolysis
In addition to increasing glycerol, glucose and amino acids in blood, cortisol also decreases …
… protein synthesis and peripheral amino acid uptake
What is Cushing Syndrome?
High cortisol level
What are the effects of Cushing Syndrome?
Person develops insulin-resistant diabetes
Cortisol can upregulate the number of ____ receptors on arterioles
____ vasoconstricting α1 ____
How can vasopressin increase blood pressure?
Cortisol activates mineralocorticoid receptors
Increases sodium reabsorption and blood volume
Does MR have a higher affinity for cortisol or aldosterone?
Same affinity
How is cortisol mineralocorticoid signaling regulated?
MR is protected from cortisol by 11β-dehydrogenase isozyme 2
Since cortisol levels are 100 times higher than aldosterone, it is important that this enzyme functions to ensure that cortisol reactions are not uncontrolled
What effect does 11β-dehydrogenase isozyme 2 have on cortisol?
Metabolizes it to inactive form
What effect does cortisol have on immunity and wound healing?
Cortisol decreases inflammation, immunity and wound healing
Why does cortisol reduce inflammation and immunity?
Acts as an anti-inflammatory molecule
Which chronic inflammatory conditions can cortisol be used in?
Skin rashes
Inflammatory kidney diseases
What are some additional cortisol functions?
Decreasing bone formation
Modulation of fetal lung development
Stimulates cognition and memory
Decreases osteoblast activity
How does cortisol modulate fetal lung development?
Production of surfactant
Why is cortisol given to mothers giving birth prematurely?
Steroid cross the placenta and hasten fetal lung development
How does cortisol stimulate cognition and memory?
Terminal maturation
Axon remodeling
Patients taking glucocorticoid drugs are at risk of …
… osteoporosis
Which regions of the brain does cortisol impact?
Hippocampus
Amygdala
Frontal Lobes
What effect does cortisol have on formation of memories?
Reinforces strong memories (good and bad)
What effect does cortisol have on cognition?
Development of alertness and cognition
What effect does cortisol have on fibroblast activity?
Decreases
Definition of stress
Any noxious stimulus increase ACTH
Describe the pathway of cortisol secretion
Stress → Paraventricular Nucleus → Limbic System → Hypothalamus (CRH) → ACTH (anterior pituitary) → Cortisol
Functions of mineralcorticoids/aldosterone
Critical for maintaining blood pressure
How can aldosterone increase blood volume?
Increases sodium reabsorption
Excretes excess potassium
Where is aldosterone produced?
Zona glomerulosa (outermost layer) of adrenal gland
What is the rate limiting enzyme in aldosterone synthesis?
Steroidogenic Acute Regulatory Protein(StAR)
Aldosterone transport
50% bound to serum albumin
30% circulates freely in blood
17% binds to CBG (also called transcortin)
Transcortin binds to cortisol and progesterone
Pathway of aldosterone affecting cells
How can MR and aldosterone affect transcription?
MR is a ligand-dependent transcription factor (TF)
Aldosterone bound to receptor acts as TF
What chemical can inhibit corticosteroid 11β-dehydrogenase isozyme 2?
Chemicals found in genuine licorice
What can inhibition of corticosteroid 11β-dehydrogenase isozyme cause?
Pseudohyperaldosteronism
The name is because mineralocorticoid effects are not caused by aldosterone, but instead by circulating cortisol that can now bind and activate the MR
What are the effects that aldosterone has on the kidneys?
Sodium reabsorption
Potassium excretion
Secretes H+ into tubular fluid
How does aldosterone increase sodium reabsorption?
Increases sodium channels on the lumen side of the cell
Na+/K+ ATPase pump on basolateral to move sodium into interstitial blood
How does aldosterone increase potassium excretion?
Na+/K+ ATPase pump on basolateral to move potassium into principal cells
Increases potassium channels on lumen side
How does aldosterone enable secretion of H+ into tubular fluid?
Stimulate H+-ATPase on the ɑ-intercalatedcellsin the collecting duct
How can hypertension be caused by primary hyperaldesteronism?
Adrenal glands continuously secrete aldosterone
Causes increased sodium and water reabsorption and hypokalemia
What are the aldosterone regulators?
Angiotensin II
Increased serum potassium
Adrenocorticotopic Hormone
How can angiotensin II affect aldosterone?
Increases aldosterone secretion through RAAS pathway during low BP
How does ACTH affect aldosterone secretion?
Affects formation of aldosterone precursors
