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431 Cards in this Set

  • Front
  • Back
the hallmark of mulitcellular life is...?
specialization
3 major communication systems?
nervous, endocrine, and immune
immune system communicates via?
cytokines
which systems maintain homeostasis?
nervous and endocrine
Which acts slower endocrine/nervous?
endocrine-has to travel thru the blood
paracrine?
ex?
local diffusion of chemical mediators
-histamine in immune
endocrine?
ex?
fluid transport of chemical mediators
- insulin in glc metabolism
autorcrine?
ex?
local action on its own secretory cell
-norepi from nerve
neuroendocrine?
ex?
endocrine like secretions out of a neuron-like secretory cell
-oxytocin
T/F:
endocrine glands are dutcless?
endocrine glands are avascular?
-T
-F, extensively vascularized
hormones receptors can be where?
membrane bound or intracellular
pheromones?
intraspecific organism-to-organism chemical messengers
allelochemicals?
interspecific organism to organism chemical messengers
Who wrote A History of Endocrinology?
Arthur Hughe
What are the major endocrine glands?
Pituitary, thyroid, Parathyroid, Pancreas, Adrenal, Ovaries, Testies
name the three types of inhibitors/stimulators of endocrine cells
ions/nutrients, neurotransmitters, hormones
where do amines develop from?
tryptophan (melatonin)
where do steroids develop from?
cholesterol
whare are eicosanoids?
small molecules made from fatty acids that sit in cell membrane
i.e. prostaglandins
what is castrati?
castrating males so that they have great opera voices (alexander moreschi)
Describe the Berthold experiment of 1849
Castrate rooster- no male development
Replace testes in different site-normal male development
Replace only 1 testes- bigger and same male development- compensatory hypertrophy
Concl: testes secrete something into blood
What is the first described hormone? by who?
Sterlin discovered Secreetin. Found that when acid went from stomach to the intestine, the intestine released secretin
Secritin stimulates pancrease to secrete biocarb to neutralize acid
Works when nerve is cut
Concl: mut be blood path ie hormone
Noble prizes for Hormone Structure, synthesis, and Assay? (3)
Sanger- structure of insulin
du Vigneaud- synthesized polypetide hormones (oxytocin and vasopressin)
Yalow-developed radioimmunoassay for measurement of hormone concentrations
who formulated the concept of homeostais?
claude bernard
What are the necessary components of endocrine regulatory systems? (8)
1. Threat/actual homeostatic imbalance
2. Coupling mechanism- activate the hormone secretory apparatus
3. Secretory apparatus
4. Hormone
5. End-organ that can respond to the hormone
6.. Detector to recognize that hormone effect has occured and signal can be shut off
7. Mechanism for removing the hormone
8. Synthetic apparatus to replenish hormone
hormone response depend on?
target cell! the type, development, position, and age of it
the connection between the hypothalamus and the pituitary glands shows which two systems working together?
the endocrine and the autonomic
What did Brown-Sequard do?
He injected himself w/ liquid from testicles, and thought he rejuvinated himself.
Started the idea of organotherapy/replacement therapy
What did Leo Stanely do?
testicle transplants in prisioners. used human and nonhuman testicles. it worked.
What did Adolf Butenandant derive from policemen's urine? what elese did he do?
adrosterone
-discovered how too make testosterone from cholesterol (1939)
whare are androgens used to treat wasting conditions in chronic illnesses?
tehy increase red blood cells
How does testerone effect sperm production?
It lowers it
the hypothalamus sees that there is high levels, so it reduces the release of LHRH, and the the pituitary gland stopes making testosterone and sperm
anabolic-androgenic hormones are all synthetic derivatives of?
testosterone
What are the 3 steps required for hormone action?
1. Hormone recognized by and bound to receptor
2. H-R complex couples w/ another mechanism or acts itself
3.generated signal (2nd messenger) alters metabolic activity
Where are the receptors for proteins/peptides/catecholamines?
in the cell membrane
Where are the receptors for steroid/thyroid hormones?
in the cytosol/nucleus
What does epeniphrene do to an alpha receptor on a blood vesel?
Beta receptor on a blood vesel?
On a liver cell (B receptor)?
contricts
dilates
breaks down clycogen and releases glc
The actual concentration of a circulation hormone reflects? (2)
the rate of release
the speed of inactivation/removal
allostasis? examples?
changes in the body that keep homeostatic system in balance
-cytokines, catecholamines, HPA axis
what can remove hormones from circulation?
target tissues, liver,kidneys
Explain the negative feed back in the Thyroid gland
1. Cold tells hypothalamus to secrete releasing hormone
2. triggers release of TSH
3. Stimulates thyroid to release thyroxine
4. increases metabolic rate and inhibits production of TSH
6. high temp-inhibits hypothalamus
What did Leowi do?
experiment on frog heart to show the existence of achetylcholine
what is dale's principle?
once cell one messenger
While claude bernard noted the idea of homeostasis, who actually coined the term?
walter Cannon
what hormones does the heart secrete?
What part of the heart secretes it?
What does int regulate (which tissues)?
Atria natriuretic factor/Peptide
-granular cells
-Regulates:
-blood pressure and volume
-Kindneys/adrenal glands-excretion of water, sodium and potassium
-Neuropetide in the brain, regulating salt/water intake, heart rate, and VP secretion
efferent nuerons of parasympathetic do what?
transmit commands to internal organds/endocrine system
afferent neurons of parasympathetic nervous system do what?
send signals to CNS
somatic system recieved afferent sensory input from?
sense orgrans
somatic system controls (efferent)?
motor output
somatic nervers are...?
mylenated, monosynaptic
ANS recieves input from? sends nerves to?
-viscera
-smooth muscles
sensory nerves in ANS are?
nonmylenated
3 divisisions of ANS? describe each
sympathetic (spinal cord-thoracolumbur)
parasympahtetic (sacrial/vagus)
Enteric-GI tract
Principle of hormone action
-are effects immediate or gradual
gradual
Principle of hormone action
-do effects act directly on behavior?
no the change probability and intensity
Principle of hormone action
-can hormones have long term effects/
yes longterm metabolic change
Principle of hormone action
-are hormones target specific?
-species specific?
yes
yes
thymic hormones aid in...?
the maturation of T cells and the dvelopment of other lymphatic organs
what is the 'life cycle" of the thymus glands
large in infants, max size at 10-12, atrophies after age 12
What do thymic glands/hormones contribute to?
-immunity
-neuroendocrine system
-reproductive system
-development of CNS
what cland is in the meidstimun, has 2 lobes, that are divided into locules w/ a cortex and a medulla?
thymus gland
what happens int he cortex of the thymus gland?
immature t cells migrate here from bone marrow and then mature
what is in the medulla of the the thymus gland?
more mature t cells
Principle of hormone action
-are effects immediate or gradual
gradual
Principle of hormone action
-do effects act directly on behavior?
no the change probability and intensity
Principle of hormone action
-can hormones have long term effects/
yes longterm metabolic change
Principle of hormone action
-are hormones target specific?
-species specific?
yes
yes
thymic hormones aid in...?
the maturation of T cells and the dvelopment of other lymphatic organs
what is the 'life cycle" of the thymus glands
large in infants, max size at 10-12, atrophies after age 12
What do thymic glands/hormones contribute to?
-immunity
-neuroendocrine system
-reproductive system
-development of CNS
what cland is in the meidstimun, has 2 lobes, that are divided into locules w/ a cortex and a medulla?
thymus gland
what happens int he cortex of the thymus gland?
immature t cells migrate here from bone marrow and then mature
what is in the medulla of the the thymus gland?
more mature t cells
How do steroid proteins get rid of their carriers?
high affinity for the receptor
or carriers have degredation of the binding protein by a specific protease (ie IGF1)
What does ectopic secretion of a hormone represent?
not under physiological regulation, symptom of a disesase process
what is a bioassay?
bilogical response of tissue (ie tissue growth)
What is a chemical assay?
altered levels of a speific chemical in a specific tissue
what is a competitive protein binding assay?
-competition betwn labeled and unlable protein for a specific binding site-radio immunoassay-asses immuno reactive levels of a hormone-uses an antibody to a specific epitope
What are the 4 steps of endocrine methodology?
1. Identify hormones/cytokines/growth factors
2. determine soure/distribution of hormone
3.Find strucutre of hormone
4.Understand regulation of hormone
Concentration of radioactive hormone relates how to the concentration of the unlabled hormoned?
inversely proportional
Radioimmmunoassay? what happens as hormone concentration increases?
competitive binding of lableled and unlabled protein
-the % of bound radioactivity decreases (curve)
IRMA? what happens as hormone concentration increases?
-double antibody where a second radioactive antibody is lableled to detect the 1st andtibody bound to labeled hormone
-radioactivity increases (linear)
ELISA? what happens as hormone concentration increases?
-enzyme links to antibody linked to radiolabeled hormone giving off a color
-color intesity increases (linear)
what do home pregancy tests detect?
hCG
Describe the metabolism of DHEA
-Precursor for Androstenedione which is converted to testosterone (or Estrone) which is converted to 5-alpha-DHT- (or estradiol)

-testosterone can also be converted to estradiol
What is intrinsa?
viagra for women
What are the 2 principle functions of hormones?
-morphogenic/development
-homeostasis
What are Hox genes?
-genes that choose a particular path of development
Where are Hox genes most obvious in humans? ex?
-Reproductive tract
-Hox10 and Hox 11 in female differentiate the endometrium and influence the menstrual cycle
how does the brain communicate w/ the immune and endocrine systems?
neuropeptides
What does neural input to the hypothalamus do?
Stimulates synthesis/secretion of releasing factors which stimulate the pituitary to produce/release hormones
What are 2 overlapping responses of the neuro, endocrine, and immune systems?
flight or fight
-chronic stress
What product connects the nerve cell to the endocrine target cell?
neurohormone
What is unique about the somatic neurons?
directly from CNS to target muscle
Describe the pre/postganglionic hormones of the SNS?
pre-ACh (sometimes dopamine)
post-norepi/epi (noradrenaline)
Describe the pre/postganglionic hormones of the PNS?
pre-ACh (sometimes dopamine)
post-ACh
In the PNS do the neurons that extend from the brainstem/lower spinal cord have ganglia close or far from the target tissue?
close
In the PNS do the neurons that extend from the IML oft spinal cord have ganglia close or far from the target tissue?
far
Where is the adrenal gland located? what are its 2 parts? How is it stimulated?
-above the kidney
-medulla and cortex
-SNS neuron from spinal cord sends ACh to it. It then release norepi/epi
corticotropin?
released by the pituitary gland, stimulates the adrenal gland, which stimulates/releases cortisol, which suppress CMI and effects the immune cells
LH/FSH?
stimulates testes and ovaries to release a variety of hormones
How does the CNS regulate the immune system?
nueroendocrine hormones/hormones that regulate inmmune function
How does the immune system regulate the CNS?
ILs and TNF, ect mess w/ homeostasis causing fatigue, fever, ect.
How does the Is affect the liver?
cytokines cause synthesis of acute phae proteins-sickness behavior
Eustress?
acute stress
-a lot of movement of luekocytes from blood to skin
-acute spikes in corticosterone
Distress
chronic stress
-not enough movement of luekocytes from blood to skin
-big spikes in corticosterone
B cells
-Where mature?
-fxns?
-mature in the marrow
-IG: antigen regonition
-differentiate into plasma cells that produce antibodies
T cells
-where mature
-fxns?
-mature in the thymus
-TCR: antigen recognition
-mature into helper/cytotoxic T cells
What are the thymic hormones?
thymosins, thymulin, thymopoietins
What do thymosin and thymopoietin do?
they cause T lymphocytes to become immunocompetent
-indirect, not direct, fighting of antigens
The stroma of the thymus?
-star shapend endothelial cells
-secrete hormones to mature t lymps
What do T helper cells do?
secrete cytokines (ILS) that organize immune response
IL-1?
IL-2?
1- T-helpers divide
2- T-cytotoxic and Bs divide
What do thymosin isotopes do to CRH, TRH, and GNRH?
Decrease CRH and TRH, Increase GNRH
What contributes to both acute and chronic weakening of the immuse system?
glucocorticoids
simple amines/ peptides have what kind of receptors?
cell surface
steroids/complex amines have what kind of receptors?
nuclear
What are the 6 basic concepts?
1. plasma levels
2.secretory patterns
3.recepors
4.plasma/tissue binding proteins
5.Feedback
6. Hormones can be measured
What contributes to both acute and chronic weakening of the immuse system?
glucocorticoids
simple amines/ peptides have what kind of receptors?
cell surface
steroids/complex amines have what kind of receptors?
nuclear
What are the 6 basic concepts?
1. plasma levels
2.secretory patterns
3.recepors
4.plasma/tissue binding proteins
5.Feedback
6. Hormones can be measured
after proinsulin is cleaved, what must form for biologica activity?
3 disulfide bonds
what is the disadvantage of monoclonal antibodies?
they can be harder to detect, even tho they are more specific and can make reproducible antibodies
What is insitu hybridization?
exposing a crystostat section to cold and labeled ligand and then using imaging to analyze
which of the assays is noncompetitive?
ELISA
What happens in a positive ELISA test?
the antibodies bind to the antigens
what is the stachard plot?
a way to determine hormone-receptor interactions
What are transgenic mice?
Mice that had parents injected w/ recombinant DNA so that they have multiple copies of genes that will be overexpressed in the genome
Inducible transgenics?
limiting where the gene will show up by limiting it to a promoter only expressed by a certain tissue or a promoter that has to be activated
endocrine glands from the mesoderm make what type of hormones?
steroids
endocrine glands from the ecto/endoderm make what type of hormones?
non-steroid hormones
cortocoids, vitamin d, and androgens are what type of hormones?
steroid
Insulin, PTH, releasing hormones, oxytocin, ect are what type of hormones?
peptide
tyhroid hormone, norepi, epi are what type of hormones?
amino acid
glycoproteins are made from what type of hormones?
peptide
which hormones are lipid derivatives?
eicosanoids
steroids
which type of hormone is most abundant?
peptide
what do protelytic enzymes do for hormones synthesis?
the cleave prohormones to make hormones
how are peptide hormones relased into the blood?
exocytosis
which hormones activate secondary messengers?
protein/peptide hormones
what is POMC?
a polyptide hormone encoded by a single gene
FSH, LH, TSH, and hCG are all?
glycoproteins
What are hormones synthesized from chains of amino acids and carboyhdrates?
glycoproteins
What are the steps for synthesis/release of peptide hormones
1. mRNA binds to preprohormone chain and brings it to ER
2.Enzymes in ER cleave it to a prohormone
3.Prohormones travel to golgi
4.Enymes cleave prohormone to hormone
5.hormones or exocytosed
6. hormones travel to target cell via blood stream
Where are prostaglandins synthesized?
almost every tissue of the body!
what are prostaglandins synthesized primarily from>?
arachodonic acid
What determines whether steriod/thyroid hormones are class 1 or class 2.
the amino acid sequence
What are the 3 patterns of hormone secretion rate control?
1. other substance (ie sugar and glc)
2. nueral control (neurotransmitters)
3.another hormone (ie TRH stimulates TSH wich stimulates Thyroid hormone which has neg feedback on both)
What stimulates release of non-steroidal hormones?
electrical, neurochemical, or hormonal stimulation
What is the fxn of pulsatile release of nonsteroidal/peptide hormones?
minimmizes down regulation of target cell receptors
which hormones have longer half-lives?
steroid/thyroid
where are hormone metabolites (breakdown products) excreted?
urine/feces
down regulation?
when tagged cells reduce the number of receptors after prolonged stimulation by a hormone
up regulation?
when exposure to stimulation increases the number of receptors
What is IL-1Ra?
a receptor antagonist that binds to IL-1 receptor not allowing IL-1Rl, which would activate the receptor, to bind
How do hormone signals get removed from the receptor/cell? (6)
1. down regulation
2. receptor inactivation
3. dephosphorylation
4. degradation
5. opposing signal/hormone
6. modifying hormone
How do hormones get removed from the blood? 4
1. Conjugation-bound to then released in urine
2. Active transport
3.excretion
4. Metabolism
MCR?
metabolic clearance rate- an expression of hormone removal
Transmembrane actions are produced by (3)?
g proteins
2.ligand-gated channels
3.transmembrane enzymes
what deactivates enzymes inside the cell? outside?
lysosomes
deactivating enzymes
prostaglandins can only act as...hormones?
parahormones/paracrine hormones
why prohormones?
stable, storage reserves, regulate the amound
which type of hormone is released as soon as synthesized?
steroid
where are carrier proteins produced?
liver
name 3 special barriers proteins have to transport thru?
blood brain
blood-testis
placental
describe the specificity of receptors
one type of receptor binds one specific hormone
3 families of membrane receptors?
ligand gated ion channel
transmembrane regulated ezympe
G-protein
describe a transmembrane-regulated ezyme receptor
tryosine kinase receptors for insulin
when insulin binds to alpha subunit, beta subunits become active and phosphorylated, increasing tyrosine kinase activity
give 2 example of g-protein receptors?
fxn of g protein receptors?
beta-adrenergic, LH
move signal from outside to inside, and stimulate/inhibit secondary messengers
what determines which secondary messenger system will be activated?
the g-protein coupled to the receptor
what do secondary messengers do?
they activate protien kinases (3rd receptor) which phosphrylaate substrate proteins. The phosphorylated substrate proteins then regulate physiological changes (4th messenger)
describe the pathway of synthesis/action of cyclic AMP
Gprotein activation--adenyl cyclase activation--increase cAMP--activation of kinase (PKA)---phosphorylation of target proteins (ie CREB, which binds to the CRE site of proteins increasing transcription and new protein syntehsis)
Name two things that break the cyclic AMP/secondary messenger system?
phosphodiesterase
phosphoprotein phosphatase
What can g proteins be linked to? (4)
ion channels
phopholipase c
adenyl cyclase
guanyl cylcase
5 basic steps of signal transduction of G proteins?
1. transform signal energy
2.protien kinase
3. secondary messenger
4. activate proteins (phosphorylation/bind calcium)
5. cell response
What triggers response w/ ligand gated receptors?
changes in ion concentration
What often occurs when an enzyme binds to a receptor enzyme?
the receptor binds dimerizes and becomes phosphosphorylated making it active
What are the steps of g protein interaction?
1. hormone binds
2. conformational change
3.exchange gdp for gtp
4.alpha subunit dissasociates
5. alpha subunit binds to enzyme that makes secondary messenger
What are the 3 major signals of GPCR?
1. cAMP
2. DAG
3. IP3
what does calcium bind to to activate enzymes?
calmodulin
what is the most common type of receptor?
gprotein
describe the basic structure of all g proteins?
7 transmembrane spanning regions
what does the alpha subunit bind to when active? Does it have high or low GTPase activity?
GTP
low
are g proteins stimulatory or inhibitory?
either!
PGE and Adenosine activate/inactivate adenyl cyclase?
inactivate
Do epi, glucagon, ACTH activate/inactivate adenyl cyclase?
activate
What does GAP do?
helps w/ GTP hydrolysis
What does GEF do?
helps w/ transition from GDP to GTP
What happens when G proteins activate phospholipase c?
calcium dependent proteins are activated
Who decided that cAMP is a secondary messenger?
sutherland
what degrades cAMP?
phosphodiesterase
what is the main target of camp in the cell?
PKA (cAMP dependent kinase)
Describe the steps of phospholipase C signaling
1. IP3 binds to calcium gated channels
2. calcium is released
3. calcium along with DAG activate PKC
4. PKC phrosphorylates target proteins
what phosphodinostidine pathways?
1. removing calcium
2. DAG hydrolyzed
3.IP3 dephosphorylated
4.PKC and CaM targets dephosphorylated
can the G beta/gamma subunits act as an activator?
yes w/ ACh in musclarinic receptors, activating potassium channels
What regulates the cAMP pathway (3)
1. has both stimulator/inhibitory receptors
2. level of cAMP
3. dephosphorylation of effector proteins (decreases cAMP levels)
Who discovered NO as a signaling molecule in the cardio system?
Fughott, Ignarrro, & Murrad
Who discovered G proteins?
Gilman and Rodbell
Describe Gillman's and Ross experiment involving AC and adrenalin
-found that cyc- doesn't make cAMP
-found the cyc+ makes cAMP
-found that cyc- w/ an inactive AC makes cAMP
-shows that cyc- aren't lacking AC, that are lacking the thing that activates AC, which are g proteins
What disease has a toxin that activates g proteins?
cholerea
What does pertussis toxin do?
blocks the inhibitory pathway- GTP never returns to GDP
What does forskolin do?
activates adenylate cyclase
role of adenylate cyclase?
to make cAMP
role of cAMP
to activate PKA (2 per PKA)by dissociating subunits
role of PKA
phosphorylate enzymes to regulate metabolism
where is insulin released from?
b cells of pancreas
where is glucagon released from
a- cells of pancreas
where is epinephrine produced?
adrenal medulla
how does cAMP-PKA affect glycogen?
stimulates break down
inhibits synthesis
give 2 examples of A-Kinase action?
1. epinephrine induced stimulus of glycogen breakdown
2.coordinate inhibition of glycogen synthesis
Describe Inositol triphospate/diacylglycerol cascade
1. g protein activated
2. phospholipase 3 activated
3. PIP makes IP3 which makes DAG
4. IP3 causes calcium to be released
5. calcium binds to calmodulin
6. kinases are activated (CaM-kinases)
7. targets are phosphorylated
8. DAG remeains anchored to membrane and activates PKC which acts on ion channels/transcription factors
gprotiens activate phospholipase A2 to create which arachidonic acid derivatives?
leukotrines and prostaglandins
signal amplification?
a small signal produces are large cell response, which amplifies the enzyme and starts a cascade
what does adrenalin do in the g protein cascade?
it causes GTP to be converted into GDP
which GEFs or GAPs activate GTPase?
GEFs
what does rhodopsin do when struck by photons?
activates PDE to convert cGMP to GMP
what hydrolyzes GTP into GDP?
the a subunit- it shuts itself off
Whats the amplifier in cAMP signaling?
adenylate cyclase
Whats the amplifier in IP3/DAG signaling?
PLC
whats the amplifier in enzyme linked receptor?
RAF, PI3K, PLC
which chain in PDGF binds to both alpha and beta receptors?
beta chain
what are ways that theraputics can intervene btwn receptor tyrosine kinsases?
1. neutral antibody
2. anti anti body
3. kinase inhibitor
4. anti dimerization
which responses is calcium/calmoduilin involved in?
TONS!
Are resting levels of cytoplasmic calcium high or low?
low
Calcium signaling is achieved by release and reuptake of Ca2+ or by synthesis
release and reuptake of Ca2+
Ca signals are local or global?
local
how do u measure calcium?
florecent dyes
what 2 pathways can use calcium as a secondary messenger?
g protein and tyrosine kinase
where is calcium stored?
extracellular
ER
What releases calcium?
activation of phospholipase c
what is the ryanodine receptor?
large calcium release channel in the SR-calium released from here activates muscle
where is calmodulin abundant?
cytoplasm of all higher cells
how many calcium can a clmodulin bind to?
4
when is CaM-kinase fully active?
when bound to calcium calmodulin and phosphorylated
what are nociceptors?
pain receptors
what is the gustatory pathway?
taste-runs through thymus
what tells u when things are salty? sour?
Sodium
hyrogen
Sweet ligands go thru what pathway?
cAMP where K depolarizes the membrane
bitter ligands go thru what pathway?
IP3 pathway
which taste ligands use Gprotein receptors?
bitter and sweet
what do all tastes cause to happen?
increase in intracellular calcium that induces transmitter release
what is phototransduction?
1. light activates all-transform of opsin
2.opsoin catalyzes gprotien
3.PDE is activated
4.cGMP hydrolyzed to
GMP
5. ligand detaches and sodium channels close
What is the capsacian receptor?
binds to VR1 (vanilloid) pain receptors, triggering calcium release and AP that lead to the production of Substance P
how does capsacian work as a topical pain reliever?
it triggers the release of substance P so that its store is depleted and pain can no longer be sensed
What makes NO?
What releases it?
What activates it?
What does it do (how does this start)?
NO synthase
endothelial cells
calmodulin
relaxes smooth muscle (triggered by ACh binding to proteins)
what is the precurosor for NO?
arginine
what regulates NO synthase?
calcium and calmodulin
how does NO relax smooth muscle?
it activates cGMP, which activates protein kinase c, which phosphroylates a phosphorylase, which dephosphorylate MLCK, which meanse that smooth muscle can't contractg
what is a good treatment for heart pain/athersclerosis?
nitroglycerin, which makes NO
what does NO bind to to relax smooth muscle?
guanyl cylcase
are NO effect local or global?
local
what inactivates NOS>
phosphorylation
where is NOS loacted?
CNS neuorons
NOS I?
neuronal
NOS II?
cytokines
NOS III?
vascular
differences between NO and Neurotransmitters?
1. diffuses out of cell-not exocytosis
2. doesn't bind to receptor-goes straight to bind to guanyl cyclase
3. made on demand-not contiunious
what aids in gas exchange between HgB and cells?
NO
Steps of NO signaling?
1. stimulated nerve releases ACh
2.ACh binds to endothelial cells
3.NOSynthase is activated
4.Arg is converted to NO
5.NO diffuses across membrane and binds to gaunyl cyclase
5.GTP is converted to cGMP
6.smooth muslce relaxes
does estrogen induce NOS (calcium increase)?
yes
which NOS is independent of Calcium concentration?
NOS II
What does NO do in the immunse system (NOS II)?
inhibits viral replication
kills bacteria
which type of PDE does viagra inhibit? how does this help
v; it is a specialized way to keep PDE from turning cGMP back to its inactive form
What happens if you have no NOS?
aggresive, hypertensive,resistant to stroke damage/septic shock, reduced inflamatory response
Where do we get cholesterol from?
1. made in liver
2. absorbed from diet
3. reverse transport from non hepatic tissues
---all end up in liver
What are the fates of cholesterol? 2
1. Bilary excretion
2. lipoprotien pathway
what are the structures of steroids/cholesterol based off of?
isoprene
what is the precursor for bile satls?
cholesterol
Describe the biosynthesis of cholesterol (5 steps)
1. Acetyl CoA converted to HMGCoA
2. HMG CoA converted to Melvanoic acid by HMGCoA reductase
3. Melvonate converted to IPP
4. IPP converted to squalene
5. Squalene converted to Cholesterol
what is the RLS of cholesterol synthesis?
the use of HMGCoA reductase
After citrate is transported into the cytoplasm and converted to acetyl coa, what converts that into AcetoacteylCoA?
thiolase
What activates HMG-CoA reductase? (cAMP, AMP, ATP, insulin)
DEphosphorylation--low cAMP---low AMP---high ATP---high insulin
What is RK?
enzyme that deactivates HMG-CoA by phosphorylating it

it becomes active when it IS phosphorylated, or when cAMP is high and insulin/ATP are low
What stimulates degredation of HMGCoA reductase?
1. cholesterol and cholesterol derivatives
What are SREBs
HMGCoA transcription factors that don't work when cholesterol is bound to them
What are statin drugs?
they look like melvonate are competitive inhibitors of HMGCoA reductase
5 steps of lipid digestion/absorption?
1. ligual and gastric lipases
2. pancreas releases lipase (phospholipases A)
3. liver's bile salts form micelles
4. micelles absorbed into epithelium
5. micelles into chylomicrons that travel thru lymphatics
What are lipoproteins?fxn
fat lipid complexes that transport fat souble compounds between tissues
What is the fxn of the lipoprotein Chylomicron?
transports FA and activates lipoprotein lipase
-dietary cholesterol to liver
What is the fxn/origin of the lipoprotein VLDL?
-carries triglycerides from liver to tissues
-made in liver
What is the fxn/origin of LDL?
-carries cholesterol from liver to tissues
-made from VLDL
what is the fxn of HDL?
collects cholesterol from tissues and brings it ot the liver
what is lipoprotein lipase?
hydrolyzes triglycerides in the capillaries
Which lipoproteins are pro-inflamatory?
Chylomicrons, HDL, VLDL
Which lipoproteins are anti-inflammatory
LDL
which lipoprotein is TG rich?
chylomicrons
what 2 organs are involved in the production of HDL?
liver and intestine
What hormones do adipose tissues make that regulate fat storage? fxn
1. Leptin-satiation
2.ASP -like insulin- stimulates glc uptake and FA reesterification
disfunctions in what receptor lead to familial hypercholesterolemia?
LDL
where is the LDL receptor most active?
liver
Basic action of LDL receptor
LDL is endocytosed, uncoated, removed from the receptor so that receptor can go back to surface, and then broken down by lososomes into amino acids, cholesterols, and fatty acids
what is tendon xanthoma?
swolen tendons due to high cholesterol
What is the role of CETP in metabolism?
cholestrol ester transfer protein converts HDL into LDL and VLDL
what should happen if you inhibit CEPT/HMGCoA reductace? Why doesn't it work?
-increase HDL and decrease LDL
-???
What is CHL?
it is made in bile salts to help solubilize/digeste nonpolar molecules
What ratio of LDL to HDL leads to heartattack?
High LDL relative to HDL (5:1)
what is artherosclerosis?
when arteries are blocked by plaque restricting blood flow and leading to blod clots
What type of ldl is proinflamatory? what does it do?
modified/oxidized
promotes differentiation of monocytes into macrophages
where does modified LDL express growth factors, proteinases, and increased cytokines?
endothelial cells
how is HDL antiinflamatory?
prevents the production of foam cells
-prevents the modification/oxidation of LDL to become proinflammatory
symptoms of CHD risk?
1.accumulated chylomicrons
2.accumulated VLDL
3. dense LDL
4. low HDL
5. Increased coagubility
what does alcohol do to lipoproteins?
increases HDL-C
what is the mechanism of statin?
1. increase NOS
2. induces apoptosis of VSM
3 major fxns of cholesterol?
1. make bile salts to digest fatty foods
2. precursor for sex hormones
3. cell membrane
What happens when 7a-hydroxylase causes cholesterol to loose cholic acid?
bile salts are made!
What is the RLS of steroid hormone synthesis from cholesterol?
StAR carring free cholesterol from the cytoplasm to the mitochondria
what organelle is responsible for lipid synthesis and detoxification of drugs?
smooth ER
what stimulates steroid synthesis?
1. increased cAMP-hydrolysis of cholesterol esters
2. increased Calcium levels and protein phosphorylation-side chain cleavage
where is the steroid hormone produced?
mitochondria
what (after cholesterol) is the precursor for all steroid hormones?
pregenolone
fxn of glucocortocoids (cortisol)?
promotes gluconeogenesis- break down of fat and protein; anti-inflammatory
fxn of mineralcortioids
increases Na reabsorption in kidney- maintains blood volume/pressure
fxns of androgens?
secondary male characteristics
fxns of vitamin d
intestinal calcium absorption
Secondary female sex hormone that regulates menstrual cycle?
progesterone
how is vitamin d aquired
product of cholesterol metabolism 7-dehydrocholesterol (i liver) converted into vitamin d3 via uv light from sun
what is the active form of vitamin d? where is this last form made?
1a,-25 dihydroxy vitamin d3 (calcitrol)
kidney
oxidases vs. oxygenases?
both catalyze oxidations, by w/ oxygenases the oxygen is directly incorporated into the molecule
what converts cholesterol to pregnenolone?
cytochrome P-450scc
what converts pregnenolone to aldosterione (which becomes androgens/estrogens)?
DHEA
how could you ensure that you have the proper steroid at the proper tissue?
localize the enzymes
role of zona glomerloas in the adrenal cortex?
makes mineral corticoids (aldosterone)
regulates blood pressure/volume
role of zona fasticulata in the adrenal cortex?
secrete glucocorticoids (cortisol)
-stress/metabolism
role of zona reticularis in the adrenal cortex?
secretes androgens (DHEA)
where are enzymes that produce steroid hormones found?
smooth ER and mitochondria
give an example of when a steroid hormone is secreted by one cell and activated by another?
adrogen secreted by gonads and activated into extrogen in the brain
21-hydroxylase turns progesterone into what 2 things? what happens when 21-hyrodxylase is defective
cortisol and aldosterone
-get androgens instead of cortisol
name 3 adrenal androgen excess diseases?
21-a-hydroxylase def
11-b-hydroxylase def
3-b-ol-dehydrogenase def
what converts cholesterol to pregnenolone?
cytochrome P-450scc
what converts pregnenolone to aldosterione (which becomes androgens/estrogens)?
DHEA
how could you ensure that you have the proper steroid at the proper tissue?
localize the enzymes
role of zona glomerloas in the adrenal cortex?
makes mineral corticoids (aldosterone)
regulates blood pressure/volume
role of zona fasticulata in the adrenal cortex?
secrete glucocorticoids (cortisol)
-stress/metabolism
where are enzymes that produce cholesterol found?
mitochondria and smooth
ER
21-hydroxylase turns progesterone into what 2 things? what happens when 21-hydroxylase is deficient?
aldosterone and cortisol
-adrogens are made instead of cortisol
Name 3 adrenal enzyme deficiencies?
21 alpha Hydroxylase deficiency
11-beta-Hydroxylase deficiency
3-beta-ol-dehydrogenase deficiency
what is cushing's syndrome
Hirsutism with weight gain
and growth retardation
what causes POLYCYSTIC OVARIAN SYMDROME?
excess adrogens of ovarian origin
What is the difference between the 5-delta and the 4-delta pathways of testosterone synthesis?
5-straight from pregnenolone
4-from progesterone
When testosterone is coverted into estradiol by aromatase, what does this do?
differentiates the male hypothalamus
what inactivates steroids? where are steroids catabolized?
-reductions and conjugation to increase their water solubility
• liver
and kidneys.
What does LH do once secreted from the pituitary?
interacts w/ leydig cells producing testosterone-systemic effect
What does FSH do once secreted from the pituitary?
interacts w/ seritoli cells, increase cAMP and transcription of adrogen biding proteins
What happens when there is reduced Sex hormone binding
globuline(SHBG)?
what causes this?
more free testosterone
obesity and chronic anovulation
What causes Hyperaldosteronism?
17-a hydroxylase is defficient, so that corisol isn't made from pregnenolone/progesterone
this causes no negative feedback on cAMP so that aldosterone is always being made
Addison's disease? cause?
adrenal gland deficiency-not enough cortisol made
no neg feed back on CRH or ATCH which causes MSH like activity causes darker pigmented skin
What is Congenital Adrenal Hyperplasias?
When pregnenolone can't be converted into progestoreone or anyother hormone...death
where do binding globulins for steroid hormones come from?
liver
Describe transcription factor regulation
Transcription factors are not synthesized response to stimulus
existing TFs are modified by a stimulus, making them active
4 basic mechanisms of transcription factor modification?
1. ligand binding
2. protein/protein interaction
3. protein modification
4. protein degradation
What happens when a ligand binds to a nuclear receptor
the HSP(inhibibory protein is displaced and then the receptor then binds to DNA
Where does the steroid bind to the receptor?
c terminus
nterminus? mRNA
What is the zinc finger motif?
the portion of a steroid receptor that binds to the Hormone response elemement (HRE) of DNA
What is CBP?
it has chromatin remodeling capabilities, it Loosens up histone-DNA
Interactions so that steroids can modify mRNA/transcription
Where is the thyroid hormone receptor always found?
in the nucleus!! (glucocorticoid can be in nucleus and cytoplasm)
Are steroid/thyroid receptors activators or supressors?
both! it depends
What is the integrator of all the systems?
the hypothalamus
Hypothalamus release of hormones is regulated by?
neurotransmitters from the brain, primarily cerebral cortex,
thalamus, and other limbic nuclei.
what connects the hypothalamus to the pitutitary gland?
the infundibular stalk
How does the hypothalamus regulate neuro and endocrine fxn? (3)
-hormone production (pituitary gland and other glands indirectly)
-ADH(vasopressin) and oxytocin production
-neural control over adrenal medula
what is the neurosecretory center that controls the pituitary?
hypothalamus
which lobe of the pitutitary is neural? non neural?
-posterior
-anterior
most neural imputs to the hypothalamus come from what system?
limbic
What types of feedback loops regulate the hypothalamus?
short, fast, and long
Name the hypothalamus hormones that increase something (4)
1. CRH -inc ACTH
2. TRH- inc TH
3.GHRH- in GH
4. GnRH- inc LH and FSH
Name the hypothalamus hormones that decrease something (2)?
PIH-inhib prolactin
Somatitistatin/GHIH- inhib GH
Vasopressin (ADH) and oxytocin are released by?
hypothalamus to pituitary
Magnocellular system of hypothalamic neurosecretory cells?
-Post Pit
-direct release of VP/Oxy into circulation
-large cells
Parvocellular system of hypothalamic neurosecretory cell?
-ant pit
-indirect release of VP/Oxy into circulation
-small cells
What does vasopressin/ADH do?
tells kidney to increase water absorption
What does oxytocin do?
stimulates smooth muscle contraction in uterus/mammary gland
What controls the release of ant pituitary hormones?
ACTH, GH, LH, FSH, Prolactin
What inhibits prolactin?
dopamine/prolactin inhibitory factor
What does somatistatin inhibit?
GH and TSH
What does dopamine inhibit?
prolactin and TSH
What types of hormones are secreted in pulses and regulate their own receptors?
hypothalmic releasing hormones
What is the suprechiasmic nucleus?
our biological clock-regulates circadium rythms
What is our supraopticnucleus?
regulates vasopresin...regulates thirst
What is the paraventricular nucleus?
makes VP, Pxy,and neurophysins from magnocellular systems
What does the posteriro hypothalimus regulate?
temperature
what does the Median Emminince (ME) regulate?
synthesis of CRH, TRH, ahd GHRH
tonic release of LHRH
Which part of the hypothalamus is the satiation center, synthesizes GRH and PRH, detects blood glc, and regulates female sexual behavior?
ventromedial
Which part of the hypothalamus controls aggresion and synthesis of CRH, TRH, and SOM?
dorsal medial
Which part of the hypothalamua controls hunger and regulation of sodium balance?
Lateral Hypothalamus (LH
Whats the hunger center? the satiety center?
LHA
VMH
regions in what area cause aphaghia?
Lateral Hypothalamic areas (LHA)
What do lesions in the ventromedial hypothalamus cause?
increased fat storage
decreased fat breakdown
What can induce eating?
-stimulating LH
-puting LH hormones (MCH and Orexin) into ventricles
What happens when leptin interacts w/ CNS? with periphery?
-high levels decrease food intake
- Metabolic effects: high levels make you use more energy
when you have more insulin you have more/less leptin?
more
How does NPY influence feeding?
energy conservation: stimulates eating and reduces metabolism during food deprivation
sends signals to lateral and paraventricular hypotahalamus
What does the opposite of NPY/AGRP?
POMC/CART
What is rimonbant?
blocks the canabanoid receptors decreasing hunger
What kind of loops regulate the thermoregulatory system of the hypothalamus?
negative feedback
nonshivering thermogenesis?
Long-term mechanism stimulating thyroid hormone release T3 and
T4.
where are thermodetectors obtained?
preoptic area of anterior pit
what are pyrogens?
interact with hypothalamus to increase temp set point: fever
what, released from hypothalamus, makes you stay awake?
orexin
Which hormone stimulaters adrenaline production and a pounding heart?
norepi
which hormone create a feeling of bliss/playfulness?
PEA
Which hormone creates memory/bodning?
vasopressin
which hormone is low when you are stressed?
seretonin
where are the receptors for pheremones?
in the volmeralnaoorgan
which part of the hyptohalamus recieves signals from the volmernaso organ
amygdyla
in which insect were pheremones discovered?
silkworms
(moths)
Lee-Boot effect?
when estrogen cycle stops w/ a bunch of female mice housed together
whitten effect?
female mice exposed to urine of male mice-estrogen cycle begins again
bruce effect?
failure to immpregnate female mice when she is exposed to her non mate
Describe the tshirt experiment?
feel like people who have a low MHC compared to you (not relatives) have better smelling sweat
what increases the presence of progesterone receptors?
estradiol
what does estrogen followed by progesterone do to sexual behavior in female rats?
increases it
what part of the hypothalamus is critical for female sexual behavior?
ventromedial nucleus of the hypothalamus
what is critical for male sexual behavior?
the MPA (the nucleus of the medial preoptic area)
How do hormones control gonadal fuction
Hypothalamus GnRH which stimulates the pituitary to make LH and FSH which stimulate the gonads to make estrogen and adrogens
What synthesizes GnRH? where
parvocellular neurosecretory cells in the MBA and AHPO
What stimulates GnRH in a female? what does this cause
A male hormone
-increased estrogen, estrus, and more GnRH
What hormone is responsible for maintaining pregnancy after ovulation
progesterone
How does oxytocin (from PVN) increase social relationships/memories?
releases norepi, norepi binds to olfactory, creates olfactory memory
what type of vole is monagamous?
prarie vohl
where is oxytocin synthesized
paraventricular/supraoptic hypothalmic nuclei
what determines the number of oxytocin receptors?
gonadal steroids
what effect does oxytocin have on montane voles?
none!
what happens to the testosterone levels of men in committed relationships?
decreases
what is in situ hybridization?
what is autoradiography?
what are these both used to detect?
-technique that uses in situ film to visualize mRNA sequences
technique that uses xray film to visualize radioactive labeled molecules
-hormone levels/hormone binding levels
What makes female prarie voles and montane voles so different?
where there oxytocin receptors are distributed
what are the central actions of arginine vasopression mediated by?
gprotein coupled receptors
what type of arginine vasopression makes different species have different social patterns?
septal
what is different in vasopressin receptors in montane vs prarier voles?
the promoter of the arginine vasopressin receptor
What technique was used to turn male montane voles monagamous? describe
promoter bashing
manipulating changes in the promoter to see which causes monogamony
Where is the vasopressin (v1a) receptor in prarie? in montane?
ventral palidum,septum