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77 Cards in this Set
- Front
- Back
where does the adrenal cortex develop from?
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urogenital ridge mesoderm…. Accessory cortical nodules are common
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most common cuase of adrenal cortex hypoplasia
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anencephaly
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primary product of fetal adrenal
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androgen (dhea) synthesis
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right adrenal vein
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goes directly to vena cava, left adrenal joins left renal vein
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action of cytochrome p450
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all hydroxylases thus insert molecular o2 into hydrocarbon bond.
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aggregates of cells beneath capsule
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glomerulosa
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columns of cells rich in lipid
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fasiculata
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eosinophillic, sparse lipid COMPACT and many contain lipofuscin
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reticularis
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the hormonally regulated rate limiting first step in the syntheisis of all steroid hormones
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removal of side chain catalyzed by CYP11A1 in the mitochondria producing pregnenolone
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how is cholesterol transported to the adrenal
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80% ldl, 20% synthesized denovo from acetate
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How does acth stimulate ldl receptor production
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cAMP
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how is cholesterol stored
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as esters ACAT in lipid droplets
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cholesterol ester hydrolase
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stimluated by ACTH free's cholesterol
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P450scc is located
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in the inner mitochondrial membrane
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what stimulates cholesterol flux into the innter mito membrane
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StAR and P450scc6
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what regulates star
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ACTH
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is STAR in placenta or brain
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no but is found in gonads
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P450scc funciton
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terminal oxidase as part of a unique mitochondrial electron transport system
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adrenodoxin
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NADPH transfers electrons to adrenodoxin reducates to adrenodoxin then to P450scc
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3BHSD
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3B hydroxysteroid dehydrogenase/delta5-4 isomerase… conversts preg to prog and 17alpa preg to 17 alpha prog and dhea to andostenedione and androstendiol to testosterone
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CYP17
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P450c17 17 alpha hydroxylase 17,20 lyase… converst pregnnolole or progesterone to the 17 hydrogylated deriitives both then undergo scission of the C17 , C20 caron bond to yield DHEA or androstenedione…. But the MAJOR RXN IS FORMING DHEA
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21 hydroxylase CYP 21A2, P450c21
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the 21 position of progesterone and 17alpha hydroxyprogesterone can be hydroxylated by this microsomal enzyme to form DOC or 11 deoxy cortisol (S) respectively.
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#1 cause of CAH
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defect in CYP21A2
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CYP11B1
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11Bhydroxylase P450c11 93% identical to P450c11AS; CYP11B2 (aldosterone synthase) and both are mitochondrial in location. CYP11B1 DOC to corticosterone and S to cortisol (F) while CYP11B2 is found exclusively in the glomerulosa and catalyzes the final 3 steps in mineralocortcoid synthesis. Uses same chain as others
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17B HSD
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many forms exist it converts androstenedione to testosterone, dhea to androstenediol, estrone to estradiol… most active in extra adrenal tissue and can funciton in oxidative and reductive modes
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CYP19
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p450arom; aromatase the enzyme essential for estrogen biosynthesis and one enzyme carries out all the steps in converting testosterone to estradiol. The enzyme is present in the ovary and in many peripheral tissues especially in adipose tissue. Not in adrenaal
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11BHSD
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conversts cortisol and corticosterone to their inactive forms. Cortisone and 11 dehydroxycoriscosterone respecively. Two major types Typ3 and II
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Type 1 11BHSD
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high Km in many glucocorticoid target tissues and function in oxidase and reductase modes
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Type II 11BHSD
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low Km is present in mineralocorticoid target tissues and protects the minearlocorticoid receptor from glucocorticoid binding and functions in an oxidase mode
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Cortisol binding
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transcortin (AKA CBG), some to albumin, only 10% is free.
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T1/2 of Cortisol
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60-90 minutes
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Cortisol and estrogen
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estrogen increases CBG levels
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CBG manufactured
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in liver, kidney disease
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major secretory product of the adrenal
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dhea
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cortisol is metabolized in the
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liver… as are steroids (but steroids also have 11B hsd)
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aldosterone t1/2
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20 minutes and only slightly bound to protein
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what regulates glucocorticoid release
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HPA
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what stimulates glucocorticoid release
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CRH (stress and diurnal rhythm)
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acth release is from
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pomc cleavage in anterior pit
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acth stimulates the release of glucorticoids (primarily cortiso) through what
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cAMP mediated and calcium via t-type channel
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DHEA secretion is stiumatled by
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ACTH not gonadotropin
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are the effects of ACTH acute or cronic
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both, stimulates cholesterol to preg and chroni stimulates adrenal growt and maintains most of the enzymes along steroidogenic pathway
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SF-1
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orphan nulcear receptor necessary for P450 expression
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genomic effects o fsteroids take
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several hours or more,
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how do glucocorticoids stimulate gluconeogenesis
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avtivate gluconeogenic enzymes in the liver; mobilize amino acids from muscle; permisseve effects on glucagon and catecholamines; enhance glycerol release from fat cell by stimulating lipolysis
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glucocorticoid and glucose updtake
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inhibited glucose uptake and metabolism in periphery
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glucocorticoids and glycogen
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gets deposited in the liver
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glucocorticoids and lypolysis
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increased
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glucocorticoid and liver protein production
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stiulate protein and rna synthesis in liver but stimulate breakdown and inhibit protein syntheiss peripherally.
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cardiovascular effects of glucocorticoids
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maintain vascular reactivity to vasoactive agents; induce cardiac proteins (maintain contractilti); maintain ability to secrete a water load; moduleate electolytes (regulate gfr, adh, and anp)
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steroids and brain
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affects mood, behavior, neural activity and biochemisty
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steroids and fibroblasts
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inhibity fibroblasts (inhibit collagen synthesis)
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steroids and type ii pneumocytes
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stimulate
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steroids and ca2++
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absorption in guy reduced and reduced kidney reabsorption
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steroid and bone
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increase resorption, decrease linear growth
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immune supressinve effects of steroids
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decrease blood concentraions of eos, basos lymphocytes, t cell proliferation and activation,
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steroids and t cells
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decreas Th1, increase Th2
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steroids and inlammation
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inhibit annexin a-1, inhibit, nfkb, inhibit PGE2 and histamine and serotoniin release
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what is the affect of mineralocoticoids
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affect ion transport in epithelial tissues
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major mineralocorticoids
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aldosterone (glomerulosa) and DOC(fasciculata) aldosterone 24X more potent than DOC
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mechanisms of mineeralocorticoids
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1. ENaC (openining of pre-existing epithelial sodium channel by SGK (serum glucocorticoid kinase) on the apical membrae) 2. induciton of Na/K ATPase on the basolateral side 3. induction of mitochondrial proteins with resultant increases in energy
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Regulators of aldosterone
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1. RAS 2. K+ 3. ACTH (transient) also posture and circadian rhythm
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when is aldosteron highest
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in morning prior to awakening
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ANP aciton on renin
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inhibits and renin secretion and modulates glomerulosa response to angiotensin II
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in steroid action what stimulates or inhibits transcriptoion
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ligand receptor
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when is feedback overridden
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during stress (infection, surgery, hypoglycemia, trauma, anxiety and depression)
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acetylcholine, gaba, serotonin, NE do what to steroid axis
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stimulate
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Endophin and steroid axis
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inhibits
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adh and ssteroid axis
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cosecreted with CRH and augmets acth release
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crh cns effects
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stimulates sns and wakening, decreases fever, supresses food intake, supresses sexual activity
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what type of patern does cortisol have
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dirunal
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what alters the cortisol pattern
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altering sleep-wake cycle… also though has intrinsic rythim in suprrachiasmatic nucleus
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cortiosl effects on glucose
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activates glycogen synthase, inactivates phophorylase
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cortisol effects on insulen
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generally diabetogenic
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benefits of cortisol function during sres
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maintani cardiovascular system, mobilize energy. Cardio effects through catecholamines and angiotensin II, engergy mobilizaiton via glucagon, epi, GH
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how does AII stimulate alsdosterone production
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IP3 and CaM kinase
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high plasma K+
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deplolarize glomerulosa and allows ca2+ entry
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