Term
| conformation and stereochemistry of steroid hormones |
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Definition
-all hormone ring fusions are trans
-many chiral carbons
-rigid
-hydrophobic
-small structural differences can have major changes in function |
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Term
| the ultimate steroid progenitor- cholesterol |
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Definition
-most commonly occurring steroid
-present in almost all organisms (especially animals)
-can be biosynthesized or supplied in diet
-major component of plasma membrane
-biosynthesis from acetyl CoA takes many enzymatic steps |
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Term
| key biosynthesis intermediate |
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Definition
| -cholesterol and P450 SCC to make pregnenolone |
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Term
| 17α hydroxylase/C17,C20 lyase |
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Definition
-adds hydroxyl at C-17= glucocorticoids
-can cleave C17-C20 bond= androgens/estrogens |
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Term
| 3β dehydrogenase (isomerase) |
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Definition
-converts hydroxyΔ5Δ6 alkene to Δ4Δ5enone
-requires NAD+ |
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Term
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Definition
-adds hydroxyl group to C21 of progestins
-on the pathway to glucocorticoids and mineralocorticoids |
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Term
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Definition
| -adds hydroxyl group to C-11 of progestins |
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Term
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Definition
-In kidney (type II, irreversible), oxidation of 11 hydroxyl to ketone inactivates glucocorticoids, important for function of mineralocorticoids
-In adipose tissue (type I, reversible), converts inactive glucocorticoid into active hormone, may be a key factor in type II diabetes |
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Term
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Definition
-ovaries- aromatase is expressed, some aromatase is expressed in adipose tissue and brain
-Leydig cells of the testis, little or no aromatase, androstenedione and testosterone predominates |
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Term
| steroid transport and excretion |
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Definition
-after biosynthesis, steroid hormones are transported in plasma by plasma transport proteins
-corticoid-binding globulin (transcortin) transports glucocorticoids and progesterone
-sex hormone binding globulin (SHBHG) transports testosterone and estradiol |
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Term
| steroid hormones have 3 major metabolic fates |
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Definition
1. oxidations to make more water soluble
2. sulfation
3. glucoronidation |
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Term
| therapeutic intervention in steroid biosynthesis- blocking P450's (chemical adrenalectomy) |
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Definition
-aminoglutethimide- inhibits a number of steroid biosynthesis enzymes, used to block steroid production in some hormone dependent tumors (breast, prostate)
-ketoconazole- antifungal at lower concentrations (ergosterol), higher concentration can inhibit P450 SCC, 17α hydroxlase, 11β hydroxylase
-can treat hyperglucocorticoid states (Cushing's)
-major problems with toxicity |
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Term
| therapeutic intervention in steroid biosynthesis- block later enzymes |
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Definition
| -metyrapone- inhibits 11β hydroxylase, used to test for pituitary function (ACTH secretion), can treat hyperglucocorticoid states (Cushing's) |
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Term
| therapeutic intervention in steroid biosynthesis- aromatase inhibitors |
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Definition
- androstenedione derivatives- exemestane (Aromasin)
-triazole derivatives- anastrazole (Arimidex), letrozole (Femara)
-selectively block conversion of testosterone to estrogen. shut down any estrogen signaling
-used to treat estrogen-responsive tumors in female reproductive tissues (breast) typically after failure of tamoxifen but are now being used as first line therapy |
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Term
| cholesterol side chain cleavage enzyme- carries out three enzymatic steps |
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Definition
1. hydroxylation at 22 position
2. hydroxylation at 20 position
3. oxidation of diol with cleavage to release side chain |
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