Term
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Definition
-important for life, essential during stress
-many different cellular effects
-increases glycogen levels in liver and circulating glucose concentrations
-potent anti-inflammatory |
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Term
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Definition
-essential for life
-effects primarily seen in kidney during stress
-regulates Na+/K+ levels
-controls water balance |
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Term
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Definition
-adrenal cortex
-zona glomerulosa- mineralocorticoid synthesis
-zona fasiculata/reticularis- glucocorticoid synthesis
-adrenal medulla- epinephrine synthesis |
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Term
| comparison of synthesis of glucocorticoid and mineralocorticoid |
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Definition
-glucocorticoid: synthesized both in response to natural biorhythm (serotonin regulated) and in response to long term stress (cold, pain, prolonged loud noise), made in large amounts (up to 25 mg/day), regulation mainly by HPA axis, but can be stimulated by sympathetic nervous system (catecholamines)
-mineralocorticoid: synthesized in response to signals of immediate stress, regulation mainly by secretion of peptides by kidney |
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Term
| regulation of aldosterone synthesis |
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Definition
-juxtaglomerular apparatus in kidney senses Na+/K+ levels, blood volume, norepinephrine
-can stimulate the production of renin
-ACTH only weakly stimulates aldosterone synthesis in zona glomerular cells
-high plasma K+ levels can directly simulate aldosterone synthesis/secretion through ion channel
-angiotension II acts through GPCR and PLC/PKC |
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Term
| target cells of mineralocorticoids |
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Definition
-kidney, salivary glands, bladder: water and electrolyte balance, aldosterone enhances the reabsorption of Na+ and the excretion of K+ in the distal renal tubules and collecting ducts (Na+, K+ ATPase), only controls approx 2% of total Na+, but is essential for survival
-cardiovascular tissues: high aldosterone levels after MI, may contribute to organ damage |
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Term
| contrasting modes of action of stress hormones: epinephrine and cortisol |
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Definition
epinephrine: binds to beta-adrenergic receptor (GPCR), initiates signal transduction cascade, induces immediate response, glycogen breakdown/glucose release
-cortisol: binds to glucocorticoid receptor (nuclear hormone receptor), regulates gene transcription, and thus translation/protein production, induces long term, persistant biological response, induces gluconeogenic enzymes |
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Term
| regulation of GC synthesis: the HPA axis |
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Definition
-secretion regulated by tropins
-corticotropin releasing hormone (CRH)- 41 amino acids
-adrenocorticotropic hormone-ACTH (corticotropin)-39 amino acids
-therapeutic ramifications of the HPA axis |
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Term
| mechanism of ACTH activation |
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Definition
G-protein coupled receptor --> adenylate cyclase -->PKA-->cholesteryl ester hydrolysis
overproduction of ACTH --> hypercorticoidism --> Cushing's syndrome |
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Term
| target cells of glucocorticoids |
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Definition
-liver, muscle, adipose tissue: increase glycogen stores and glucose levels
-immune system: anti-inflammatory, causes thymus apoptosis in children
-vasculature: increased sensitivity to vasoactive agents |
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Term
| major regulatory roles-gluconeogenesis |
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Definition
-primarily positive GRE action
-upregulate expression of phsophoenolpyruvate carboxykinase (PEPCK)-rate limiting step in glucose production
-upregulates expression of glucose 6-phosphatase
-stimulates release of fatty acids and amino acids from tissues (gene?)
-increases the activity of glucagon (insulin repressor)
2. anti-inflammatory |
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Term
| major regulatory roles- anti-inflammatory |
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Definition
-positive GREs: synthesis of lippcortin, inhibitor of phospholipase A2, prevents arachadonic acid release, synthesis of IkB
-negative GRE action and interactions with other transcription factors: decreased expression of cytokine genes (IL-1, TNFa, and GM-CSF), decreased expression of PLA2 |
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Term
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Definition
mineralocorticoid receptor (Type I corticosteroid receptor)
-found in distal renal tubules of kidney
-increase Na+, K+ ATPase activity
-aldosterone has 800x more Na+ retention activity than cortisol (cortisol binds with equal affinity)
glucocorticoid receptor (Type II corticosteroid receptor)
-found in liver, muscle, bone, lymphocytes, pituitary
-share same hormone response element |
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Term
| hormone response elements |
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Definition
| DBD's of activated dimers bind to specific DNA sequences called Hormone Responsive Elements, upstream of steroid responsive genes. binding alters rate of transcription |
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Term
| 3 possible effects on transcription |
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Definition
-positive HRE: DNA binding increases transcription factor binding, accelerating transcription rate
-negative HRE: DNA binding inhibits transcription factor binding, suppressing transcription
-protein-protein interaction: steroid/receptor dimer binds to transcription factors, modulating their activity. DNA binding not essential |
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Term
| mechanism of repression- Nuclear Factor kappa beta (NFkB) |
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Definition
1. NFkB is a heterodimer- bound to an inhibitor protein IkB
2. immune cell activation removes IkB inhibition of NFkB and NFkB moves to the nucleus. turns on cytokine transcription |
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Term
| GR repression of NFkB action |
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Definition
-liganded GR binds to NFkB, prevents binding of NFkB to its response element --> inhibition of cytokine transcription
-similar behavior with AP-1 transcription factor |
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