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75 Cards in this Set
- Front
- Back
Conversion of the C27 cholesterol ring involves the rate-limiting, irreversible cleavage of
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the 6-C residue from cholesterol
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Steroids with 21 C atoms are known as
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Pregnanes
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produced from progesterone in the zona glomerulosa
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aldosterone
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an esterogen, produced in the ovary responsible for 2ndary sex characteristics
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estrodiol
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Principal mineralcorticoid
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aldosterone
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principle glucocorticoid
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cortisol
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symthesized from progesterone in zona fasciculata
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cortisol
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all steroid hormones exert action by passing through plasma membrane and binding to
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intracellular receptors
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specific nucleotide sequences bing to hormone-receptor complexes
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Hormone response elements HREs
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Leutinizing hormone stimulates sythensis of
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progesterone
testosterone |
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ACTH hormone stimulates sythensis of
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cortisol
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FSH hormone stimulates sythensis of
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estradiol
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Angiotensin I and II stimulates sythensis of
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aldosterone
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committed and reat-limiting step of steroid synthesis
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cleavage of a 6-carbon group from cholesterol
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the NZ system catalysing the 6-C group is the
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P450 linked side cleavage NZ
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P450 sc or desmolase is found in the __________ of steroid producing cells
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mitochondria (not in significant quantities in other cells)
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desmolase consists of cyt P450 and
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adrenadoxin (a P450 reductant)
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Desmolase
1) cAMP stimulates PKS - leads to |
phosphorylation of cholesterol-ester esterase
↑ concentrations of cholesterol |
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Desmolase
2) gene for desmolase contain cAMP regulated reg. element CRE binds cAMP and ____ |
↑ levels of desmolase RNA transcription
↑ levels of NZ |
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Cholesterol is a NEGATIVE feedback regulator of HMG CoA reductase activity. When cytosolic cholesterol is depleted ____
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de novo synthesis of cholesterol is stimulated
HMG CoA reductase is freed of restraints |
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Subsequent to desmolase activity, prenenolone ____
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moves to cytosol - further processed
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hydroxulases involved in synthesis of steroid hormones are members of
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Cyt P450 Nzs
Indictes site of hydroxylation eg. P450c17 |
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Adrenal cortex produces 3 major classes of steroid hormones
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glucocorticoids
mineralcorticoids androgens |
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Adrenal insufficiency is know as
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Addison's disease
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Zona glomerulosa cells lack P450c17 that converst pregnenolone and
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progesterone to C17 hydroxylated analogs
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Zona glomerulosa
pathways to glucocorticoids (___) and andgrogens (____) are blocked |
deoxycortisol and cortisol
DHEA and androstenedione |
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Zona glomerulosa
unique - contain NZ that converts corticosteron to |
aldosterone - principal mineralcorticoid
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The NZ P450c18 or 18a-hydeoxylase is also called
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aldosterone synthase
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Zona Fasciculata and Zona reticularis lack P450c18 and cannot convert corticosterone to
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aldosterone
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Zona Fasciculata and Zona reticularis contain P450c17 and produce
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cortisol - the major glucocorticoid
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Zona Fasciculata and Zona reticularis contain C17, 20 lyase whose activity is resp. for producing
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the androgens
DHEA androstenedione |
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P450ssc is converted to androgens or
11-deocycortisol and 11-deoxycorticosterone by NZs in the |
Endoplasmic reticulum
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P450ssc
after conversion - renter the ______ and NZs convert to |
mitochondria
glucocorticoids mineralcorticoids |
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ACTH of hypothalamus
regulates hormone production of |
Zona Fasciculata
Zona Reticularis |
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ACTH receptors in the plasma membrane activates
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aednylate cyclase → 2nd messenger cAMP
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ACTH - clssic feedback loop CRH
ACTH and |
cortisol
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Mineralcorticoid secretion from the _____
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zona glomerulosa
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Kidney protease acts on → Angoistensinogen from liver → stim zona glom cells by binding plasma membrane receptor coupled to
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Phospholipase C
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This angiotensin II and III bind to their receptors → leads to activation of _____ and elevated ______
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activates PKC
↑ intracellular Ca++ ↑ P450 SSC ↑ aldosterone |
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In the kidney aldosterone regulates Na+ retention by stimulating gene expression of
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mRNA for Na+/K+ ATPase responsible for re-accumulation of Na+ from urine
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Drugs widely used to lower blood pressure
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ACE inhibitors
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ACE inhibits compete with
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NZ that convert angiotensis I to active angiotensin II and III
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Feedback loop of ACE imhibitors os closed by
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K+ - potent stimulator of aldosterone
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K+ increases aldosterone secretion by depolarizing the plasma membrane of _____ opening voltage gated
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Zona glomerusola cells - Ca++ channel
↑ cytoplasmic Ca++and stimulation of Ca++ dep processes |
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Low levels of of circulating sex hormones reduce the _____ and lead to elevation of FSH and LH
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feedback inhibition of GnRH synthsis (long loop)
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FSH and LH bind to gonad tissue and stimulate P450SSC activity resulting in sex hormone production via
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cAMP
PKA mediated pathways |
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Andenylate cyclase activation is coupled to the binding of
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LH to plasma membrane receptors
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testes and ovaries contain an additional NZ ______ that enables androgens to be converted to
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17bHSD
testosterone |
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In males LH binds to ___ cells and stimulates _____
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Leydig
testosterone |
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Testosterone is secreted into the plasma and also carried in the ____ cells by ________
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Sertoli
Androgen Binding proein (ABP) |
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In Sertoli cells the D4 double bond of testosterone reduced producing
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dihydrotestosterone (DHT)
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testosterone and DHT are carried in the plasma and delivered to tissues by
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gonadal-steroid binding globulin (GBG)
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In some tissues testosterone can be converted to DHT - the most ______
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potent of the male steroid hormone
(testosterone sometimes considered a prohormone) |
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Testosterone can also be produced int the ____ cells, but it is regulated by _____
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Sertoli
FSH |
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FSH also stimulates Sertoli cells to produce ____ which transports Testosterone and DHT from ____ to ______
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APB
Leydig cells to sites of spermatogenesis |
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There testosterone acts to stimulate
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sperm development and
proten synthesis |
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In females, LH binds to ______ where is stimulates synth of ______ by the usual
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thecal cells of the ovary
androstenedione and testosterone cAMP and PKA reg pathways |
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Aromatase is responsible for the final ____
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conversion of into estrogen
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Aromatase
complex NZ in ______ found in the |
ER
ovary and other tissues |
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Aromatase
its hydroxylations and dehydrations culminate in the ____ |
aromatization of the A ring of androgens
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Synthesis of testosterone and androstenedione occurs from _______
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cholesterol
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Aromatase activity is also found in ______ but the activity is stimulated by
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granulosa cells
FSH |
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Normally thecal cell androgens are produced in response to ______ and diffuse to _________
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LH
granulosa cells |
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Granulosa cell aromatase converts androgens to ____-
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estrogens
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As granulosa cells mature they develop a large number of _____ receptors in the _____ ↑ wuantity of estrogen produced
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LH
plasma membrane |
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granulosa cell estrogens are largely secreted into
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follicular fluid
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Thecal cell estrogens are secreted into the ____ where they are delivered to taget tissues by
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circulation
GBG (also used to transport testosterone |
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The binding of hormone, and/or phosphorylation of receptor Heat Schok Proteins (HSP) initiate movemnt of
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nuclear receptor to the nucleus
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HREs are on the DNA in the
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promoter egion
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The hormone receptor complex often binds as homodimer to _____ and bends the DNA at the _______
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palindromically oriented HREs
site of binding |
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Disaggregation - hormone level falls - movement of receptor back to _____ where ____ can bind
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cytoplasm
HSPs |
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The steroid and thyroid family of receptors have three distinct domains
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a ligand binding region
a DNA binding domain and a transcriptional reg domain |
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Binding of thyroid hormone to its receptor results in
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release of rceptor from the DNA
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Binding of glucocorticoid leads to _____ of ligand-binding receptor from cytosol to ____
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translocation
nucleus |
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The receptors for the retinoids are ID as _____ and have three subtypes
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RARs
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