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13 Cards in this Set
- Front
- Back
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characteristics of steroid hormones |
-secreted by steroidogenic glands -enzymatically derived from cholesterol -recognized by specific steroid hormone intracellular receptors -5 classes: progestins, glucocorticoids, mineralocoricoids, androgens, and estrogens -regulated by the level of synthesis -excreted in the urine and sometimes bile -transported with a binding/transport proteins (primarily binding globulins made by the liver) |
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steroid hormone synthesis common to all steroidogenic cells |
-can synthesize cholesterol from acetate or import LDLs via LDLR-mediated endocytosis or HDLs via SR-B1 and diffusion -can synthesize cholesterol from acetate, store it with ACAT, and release it via HSL -have CYP11A1 (mito-requires transport with stAR) and 3beta HSD (SER and mito), to do first two reactions |
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peripheral conversion |
-steroid hormones can be released as inactive precursors and converted in peripheral organs -e.g. androstendione is released from ovarian theca cells and converted to estradiol in the granulosa cells or testosterone or estradiol in peripheral organs |
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configuration of steroidogenic glands |
-usually in an axis (HP-adrenal or gonad) except aldosterone, placental steroid hormones, and nuerosteroids -responses to tropic hormones can be fast, medium, or long term |
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nuclear steroid hormone receptors structure |
-ligand binding domain gives specificity -heat-shock protein-binding domain -nuclear translocation domain -dimerization domain -DNA binding domain -co-regulatory binding domain(s) (e.g. activating function domains AF1 and AF2) |
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nuclear steroid hormone receptors MOA |
-hormone passes through membrane -receptor may be in the cytoplasm tethered to a chaperone (e.g. HSP90) or in the nucleus -hormone binding causes dissociation of HSP90 and translocation to nucleus -hormone-receptor complex binds specific DNA (often as dimer) and recruits co-regulatory proteins (alter chromatin) -mixed agonist/antagonist effects due to different levels of co-activators and co-repressor in different cells |
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cancer |
-can promote progression of cancer in non-endocrine target organs (e.g. breast, uterus, prostate) -2/3 of newly diagnosed invasive breast cancer express ERalpha and are dependent on estradiol for growth |
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CYP11A1 |
cholesterol side chain cleavage enzyme -common to all steroid synthesis pathways -localized in the mitochondria, so requires transport proteins to act on cholesterol |
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CYP family |
cytochrome P450 family -mono-oxygenases requiring molecular o2 and NADPH -usually add hydroxyl group -located in inner mitochondria membrane and SER |
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3Beta-HSD |
3beta hydroxysteroid dehydrogenase -type i in placenta and skin; type ii in steriodogenic glands -flips the double bond from carbons 5-6 to 4-5 (D5-->D4); required for all bioactive steroids -in the SER -important in peripheral conversion |
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17beta-HSD |
17beta hydroxysteroid dehydrogenase -5 isoforms exist, some activate some inactivate -only relevant for androgens and estrogens -reduces ketone on C17 to hydroxyl -in SER -important in peripheral conversion |
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steroidogenic gland response to tropic hormones |
-fast: inc. HSL to release of cholesterol from cholesterol ester lipid droplets and stAR to transfer cholesterol to mitochondria -medium: inc. synthesis of steroidogenic hormones, LDLR, and SR-B1 -long: growth of gland |
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classes of steroid hormone receptors |
-progeterone: binds progesterone -glucocorticoid: binds cortisol -mineralocorticoid: binds aldosterone and deoxycorticosterone -estrogen: binds estradiol -androgen: binds testosterone and dihydrotestosterone |
