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79 Cards in this Set
- Front
- Back
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What is the outermost zone of the adrenal cortex?
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Zona Glomerulosa
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What does the Zona Glomerulosa synthesize?
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Mineralcorticoid Aldosterone
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What is the middle zone of the adrenal cortex?
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Zona Fasciculata
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What is the innermost layer of the adrenal cortex?
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Zona Reticularis
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What does the Zona Reticularis synthesize?
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Cortisol
Dehydroepiandorosterone (DHEA) Androstenedione |
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What is the adrenal medulla derived from?
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Neural crest
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Where is corticotropin releasing hormone synthesized?
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Hypothalamus
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Where are the CRFR1 receptors?
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Anterior pituitary corticotrophs, it is a Gs-proteind coupled receptor
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What promotes the release of CRF?
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Proinflammatory cytokines and chronic stress
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What does Corticotroph hormone promote?
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Increased synthesis of the preprohormone propiomelanocortin
Cleavage of POMC and release of: MSH, ACTH, alpha-lipotropin |
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What are the products of pro-opiomelanocortin?
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ACTH
MSH (melanostimulating hormone) |
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What does MSH stimulate?
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Melanocyte proliferation and pigmentation
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Where is ACTH synthesized?
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Corticotrophs
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Where does ACTH bind?
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Binds melanocortin-2-receptor in adrenal cortical cells
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What influence does ACTH have once it is bound to its receptor?
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Rapidly promotes side-chain cleavage enzyme synthesis in adrenal cortex…this reaction enzyme is required for cholesterol conversion to pregnenolone and this is a rate limiting step in adrenal steroid synthesis
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What is the principal melanocortin receptor in the skin that regulates pigmentation?
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MC1-R
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How can chronically elevated ACTh induce skin hyper-pigmentation?
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ACTH at high levels can also bind to MC1-R in the skin
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What is the primary ACTH receptor?
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MC2-R
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Where is MC2-R predominantly expressed?
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Adrenal cortex
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What is stress-induced lipolysis?
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MC2-R is expressed in adipocytes and therefore mediates stress-induced lipolysis via central ACTH release
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Where is MC3-R expressed?
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In the brain
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What does MC3-R regulate and what happens if it is knocked out?
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Regulates food intake and energy homeostasis
Knockouts are obese |
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Where is MC4-R expressed?
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In the CNS (mainly the hypothalamus) , the GI tract, and the placenta
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What is MC4-R involved in?
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Food intake regulation
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Where is MC5-R expressed?
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Adrenals
Skin Stomach Lung Spleen |
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What is MC5-R involved with?
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Sebum production
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What is the primary active glucocorticoids?
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Cortisol
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What receptors do glucocorticoids bind to?
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Glucocorticoid receptors
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What can a deficiency in gluocorticoids lead to?
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Hypoglycemia
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What is the primary mineralocorticoid? What does it do?
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Aldosterone, it promotes salt and water retention by the kidney
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What are the sex steroids?
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Dehydroepiandrosterone (DHEA)
Androstenedione Testosterone |
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What receptor do sex steroids bind to?
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Androgen receptors (AR)
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Is most of cortisol free or bound?
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90% circulates bound
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What is most cortisol bound to?
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60% bound to corticotropin binding globulin (transcortin) = CBG
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What is 30% of cortisol bound to?
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albumin
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How does increased cortisol and liver cirrhosis effect CBG (transcortin)?
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Decreases CBG
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How does estrogens and pregnancy effect CBG (transcortin)?
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Increases CBG
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Where are glucocorticoid receptors located?
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Receptors are in the cytoplasm of a cell
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How do glucocorticoid receptor homodimers function?
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Act as transcription factors, so they bind to genes with GRE which recruits transcriptional cofactors and initiates or inhibits transcription
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Where are glucocorticoid receptors expressed?
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In nearly every cell
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In general what do glucocorticoid/glucocorticoid receptors help manage in the body?
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Regulates development, metabolism, and immune response
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What is NR3C2 a receptor for?
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Aldosterone ( a mineralocorticoid receptor)
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Where do you find the mineralocorticoid receptor (MR)?
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Kidney
Colon Sweat Glands Heart Hippocampus Brown Adipose |
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Do MR have stronger affinity for aldosterone or cortisol?
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Equal
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What enzyme intracellularly converts active glucocorticoid to inactive steroid?
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11 beta hydroxylase Type 2
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Where do you find 11 beta hydroxyls Type 2?
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Kidney
Colon Salivary Gland Placenta Fetus |
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What converts inactive steroids into active steroids?
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11 beta hydroxylase type 1
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Where do you find 11 beta hydroxyls type 1?
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Liver adipose,
lung Vascular tissue CNS Macrophages |
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Are many synthetic glucocorticoids already active or do they need to be converted?
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Need to be converted
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Where does most of the glucocorticoid metabolism occur?
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In the liver
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How do glucocorticoids effect carbohydrate metabolism?
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Increase gluconeogenesis
Decreased glucose uptake by muscle and fat Increased plasma glucose Increased hepatic glycogen synthesis |
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How do glucocorticoids effect fat metabolism?
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Increase peripheral lipolysis
Increase plasma free fatty acids |
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How do glucocorticoids effect protein metabolism?
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Increase proteolysis
Increase urinary nitrogen excretion |
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At sustained elevated levels of glucocorticoid, how does this impact TSH release?
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Decreases TSH release
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At sustained elevated levels of glucocorticoid, how does this impact adipose tissue?
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Visceral obesity
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At sustained elevated levels of glucocorticoid, how does this impact skin/muscle/connective tissue?
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Collagen breakdown
Skin thinning Muscular atrophy |
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At sustained elevated levels of glucocorticoid, how does this impact bone?
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Decreased osteoblast activity
Decreased bone mass and osteoporosis |
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At sustained elevated levels of glucocorticoid, how does this impact growth in children?
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Decreased linear growth in children
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At sustained elevated levels of glucocorticoid, how does this impact the immune system?
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Anti-inflammatory action
Immunosuppression |
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What are all steroids synthesized from?
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Cholesterol
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What is the rate limiting step in steroid synthesis?
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Cyp11A1--side chain cleavage
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Congenital Adrenal Hyperplasia most commonly is due to what 2 common mutations?
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Cyp21A (21-hydroxylase)
Cyp11B1 (11B- hydroxylase |
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What enzyme do zona glomerulosa cells lack?
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17alpha-hyroxylase, but they express aldosterone synthase
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What are the effects of congenital 21-hydroxylase deficiency?
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Decreased cortisol and aldosterone
Increased ACTH Increased enzymes and precursors Increased androgens Sx: virilization, hypotension |
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What are the effects of 11beta-hydroxylase deficiency?
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Decreased cortisol, corticosterone, and aldosterone
Increased ACTH Increased androgens Increased deoxycorticosteroids Sx: virlization and hypertension due to mineralocorticoid activity of deoxycorticosterone and 11 dexycortisol |
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Towards aldosterone production, normal ACTH is ____ and at high levels ACTH is _____
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Tonic
Stimulatory |
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Is angiotensin II stimulatory or inhibitory to aldosterone production?
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Stimulatory
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Is there feedback of aldosterone on ACTH?
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No
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What's the blood profile of someone with Cushing Disease?
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Increased ACTH (hyper pigmentation)
Increased cortisol +/- aldosterone |
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What's the blood profile of cushing syndrome (such as caused by adrenal tumor)
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Increased cortisol
Decreased ACTH |
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What are the sx of cushing syndrome/disease (clinically)?
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Moon face
Fat pads (buffalo hump) Thin skin High BP Red Striae (look like stretch marks) Obese abdomen Thin arms and legs Poor wound healing Osteoporosis |
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What is Addisons disease?
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D/T immune mediated destruction of adrenal cortex
Congenital adrenal hyperplasia Decreased cortisol Decreased aldosterone Compensatory ACTH (Increased POMC) |
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What is iatrogenic (secondary) adrenal insufficiency caused by?
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Sudden withdrawal of exogenous glucocorticoid because the exogenous cortisol causes decreased ACTH
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What are the common sx of adrenal insufficiency?
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Fatigue and weakness
Anorexia and loss of appetite Diarrhea Hyperpigmentation |
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Production of ____ is the rate limiting step in corticoids?
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Production of pregneolone
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What enzyme is responsible for progesterone conversion to glucocortioids?
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21 hydroxylase
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Do you see hypotension or hypertension with 21 hydroxyls deficiency?
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Hypotension
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What enzyme is responsible for converting deoxycorticosteroids to glucocorticoids and mineral corticoids?
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11B-hydroxylase
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Would you see hypotension or hypertension in 11B-hydroxylase deficiency? Why?
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Hypertension, because although you can't make aldosterone, deoxycorticosterone and 11 deoxycortisol have weak mineral corticoid activity and since they are in excess it leads to hypertension
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