Lecture 20 3/7/24 Flashcards
What is the starting material for all hormones?
cholesterol
Which enzyme is shared by all zones of the adrenal cortex?
cholesterol desmolase
What is the role of cholesterol desmolase?
required to activate cholesterol for further chemical modification
Which hormone must be present for cholesterol desmolase to be expressed?
ACTH
Which enzyme is present in the zona glomerulosa?
aldosterone synthase
What is the role of aldosterone synthase?
responsible for the synthesis of aldosterone from corticosterone
Which system is responsible for stimulation of aldosterone synthase?
renin angiotensin system
Why is it important that most chemical reactions are one way?
enzyme deficiency causes steroids to accumulate behind the blockades
When is enzyme deficiency more serious/potentially lethal?
when enzyme failure occurs close to cholesterol, causing adrenal cortex deficiency
What are the characteristics of CRH?
-secreted in median eminence of hypothalamus
-transported in portal pituitary vessels to adenohypophysis
-stimulates secretion of ACTH/family
What are the characteristics of ACTH?
-concentrations of ACTH and cortisol in blood are increased by CRH
-half-life of about 10 minutes
What blocks CRH and ACTH secretions?
endogenous and exogenous glucocorticoids
What steps occur when ACTH binds its receptor?
-a G protein activates adenylcyclase ->
-formation of cAMP ->
-activation of protein kinase A ->
-phosphorylation of cholesterol ester lipase
What is the first hormone-dependent rate limiting step in the ACTH stim. of zona fasciculata cells?
transportation of cholesterol through the mitochondrial membrane
What is StAR?
a small but fundamental transport protein that is induced by ACTH
What is the role of cholesterol desmolase in the mitochondria?
conversion of cholesterol to pregnenolone
Why must pregnenolone be transferred from the mitochondria to the smooth ER?
pregnenolone cannot be converted to cortisol directly
How is the smooth ER involved in cortisol production?
it converts pregnenolone into 11-deoxycortisol, which can go back to the mitochondria for conversion into cortisol
Which plasma proteins are involved in cortisol transport?
-CBG/transcortin
-albumin
What are the characteristics of CBG in cortisol binding?
-relatively low conc. in plasma
-only one cortisol receptor site per molecule
-low capacity for binding cortisol despite the molecule binding strongly
-binds majority of cortisol in blood (75%)
What are the characteristics of albumin in cortisol binding?
-much greater capacity for binding cortisol
-weaker binding to cortisol
-binds about 15% of cortisol in blood
What are the main functions of carrier proteins?
-protect cortisol from kidney excretion and liver inactivation
-provide water solubility to cortisol
-provide dynamic storage for hormone and regulate hormone availability to effector tissues
Which conditions lead to increased total cortisol and increased CBG?
-pregnancy
-estrogen therapy
Which conditions lead to decreased total cortisol and decreased CBG?
-chronic liver disease
-starvation
-nephrotic syndrome
How does cortisol lead to immunosuppression?
-increased neutrophil demargination/decreased neutrophil emigration
-decreased macrophage function
-decreased lymphocytes in circulation
-decreased eosinophils in circulation
How does cortisol lead to anti-inflammatory responses?
-decreased release of pro-inflammatory enzymes
-blockage of arachidonic acid metabolism
-decreased release of macrophage and lymphocyte-derived cytokines and interleukins
What effect does cortisol have at normal concentrations?
stops inflammatory processes
How does cortisol impact carbohydrate metabolism?
-hyperglycemic effect
-gluconeogenesis
-increased insulin resistance
-glycogenosynthesis
How does cortisol impact protein metabolism?
-catabolic effect
-decreased muscle mass
-decreased collagen/bone formation
-increased free AAs in serum
-increased excretion of nitrogen in urine
How does cortisol impact lipid metabolism?
-lipolysis
-lipogenesis
-redistribution of body fat
How does cortisol impact mineral metabolism?
-decreased serum Ca++
-decreased intestinal reabsorption
-increased renal excretion
How does cortisol impact water metabolism?
increased water diuresis
Where does the majority of aldosterone metabolism occur?
liver and kidney
What is the action of aldosterone?
-Na+ reabsorption
-K+ and H+ excretion
How does the pituitary impact aldosterone regulation?
aldosterone regulation is pituitary independent
What are the characteristics of the adrenal medulla?
-catecholamine-secreting cells are chromaffin cells
-majority of cells secrete epinephrine over norepinephrine
What stimulates the adrenal medulla?
-sympathetic neurons
-cortisol
What are the characteristics of catecholamines in the plasma?
-50% loosely bound to albumin
-50% free
-half-life of about 2 minutes
What are the metabolic effects of catecholamines?
-glycogenolysis in skeletal muscle and liver -> hyperglycemia
-lipolysis and fat mobilization
-stimulation of basal metabolic rate and calorigenesis
What are the cardiovascular effects of catecholamines?
-tachycardia and increased BP
-vasoconstriction in the skin and GI tract
-vasodilation in skeletal muscle and liver
-smooth muscle/bronchiole dilation
