Adrenal Hormones Flashcards
P450scc
Trivial name: Cholesterol Side Chain
Cleavage
Info: First step that occurs
in mitochondria
Inhibitors: aminoglutethimide
3b-HSD
Trivial name: 3b-hydroxysteroid
dehydrogenase
Info: Intros ketone in 3
position on A ring
Inhibitors: trilostane
P450c17
Trivial name: 17a-hydroxylase; 17,20-lyase
Info: Introduces hydroxide in 17 position; cleaves stuff off if androgen is wanted
Inhibitors: ketoconazole
P450c21
Trivial name: 21-hydroxylase
Info: Introduces
hydroxide in 21 position
Inhibitors: ketoconazole
P450c11b
Trivial name: 11b-hydroxylase
Info: Introduces
hydroxide in 11b position
Inhibitors: Metyrapone;
ketoconazole
P450aldo
Trivial name: Aldosterone synthase (11band 18-hydroxylase, 18-
hydroxysteroid
dehydrogenase)
Info: One enzyme that
does 3 modifications
Inhibitors: Metyrapone;
ketoconazole
Mineralocorticoid (aldosterone) biosynthesis
Location: glomerulosa
Lacks P450c17 expression thus cannot produce glucocorticoid/androgens
Glucocorticoid (cortisol) biosynthesis
Location: fasciculata
P450c17 has impaired 17,20-lyase activity
Minor androgen synthesis
Lacks aldosterone synthase expression thus cannot
produce mineralocorticoids
Androgen pathway
Location: Reticularis
Lacks significant 21-hydroxylase expression
Lyase (Desmolase)
cleaves C-C bond in substate with formation of two pdts by a process that’s not
hydrolysis (i.e. oxidoreductase/transferase)
Hydroxylase
add/removal of -OH moiety
Hydroxysteroid dehydrogenase
ketone à alcohol (and reverse rxn)
Aminoglutethimide
How?
inhibits first step of hormone synthesis like not having a cortex
Highdose: inhibition of first step –> treatment for Cushing’s
Lowdose: inhibition of aromatase in peripheral tissues –> 3rd line BC treatment
Trilostane
How?
competitively inhibits 3b-hydroxysteroid dehydrogenase (SERM); allosteric modulator of ER
Ketoconazole
How?
Inhibits adrenal steroid enzymes P450c17 (17a-hydroxylase and 17,20-lyase) and 11b-hydroxylase
Antifungal agent –> blocks ergosterol biosynthesis in fungi
Metyrapone
How?
Inhibits 11b-hydroxylase
used for cushing’s
Mineralocorticoid Receptor Competitive Antagonist
Spironolactone–>”Potassium sparing diuretic”
Blocks aldosterone receptors
Glucocorticoid Receptor Antagonist
Mifepristone–> used for cushing’s and also considered abortion pill
Progesterone receptor antagonist
What part of the adrenocorticoid molecule is the most important for binding?
C and D rings, especially 11-18, 20, 21
How do bulky substituents on beta side of compound affect glucocorticoid and mineralocorticoid activity?
no glucocorticoid activity;
mineralocorticoid activity present
How do bulky substituents on alpha side of compound affect glucocorticoid and mineralocorticoid activity?
glucocorticoid activity present; no
mineralocorticoid activity
What are substituents that increase glucocorticoid/mineralocorticoid activity?
1-ene
9alpha-F
9alpha-Cl
What are substituents that decrease salt retention?
16alpha-OH (16alpha, 17alpha-ketal)
16 alpha or 16beta-methyl
6alpha-methyl
What are substituents that increase lipid solubility?
CHECK NOTES
What are substituents that increase water solubility?
CHECK NOTES
What are substituents that decrease inactivation?
Methyl groups
What are some examples of mineralocorticoids?
Aldosterone
Deoxycorticosterone
Fludrocortisone
Which glucocorticoids have moderate-low salt retention?
Prednisolone
Which glucocorticoids have low-no salt retention?
Methylprednisolone, Dexamethasone, Betamethasone, Beclomethasone, Triamcinolone
