Endocrinology Gill Quiz 1 Exam 3

The adrenal medulla makes up __ of the adrenal gland

10%

The adrenal medulla creates

Catecholemines

The adrenal cortex makes up ___ of the adrenal gland

90%

The adrenal cortex creates

steroids

Oliver and Shafer in 1895 determine

adrenal gland extract cause pressor activity

Abel in 1899

isolated epinephrine

-has a dual effect

Epinephrine as a vasopressor

Vasoconstriction

Epinephrine as a vasodepressor

Vasodilation

Earl Sutherland in 1974

found epinephrine is cAMP mediated

Pheochromoblast are

stem cells with an ectodermal orgin

Pheochromoblast become

Pheochromocytes

Pheochromocytes become

Chromaffin cells

Chromaffin cells react to

Chromic acid (Potassium dichromate)

Chromic acid becomes ____ an oxidized version which oxidizes _______ into a ____compound

Cr (VI)

Epinephrine

Dark

Neural crust cells become _______ ganglia which become the _______ chain

Sympathetic

Sympathetic

The chromaffin cells are found in the Chromaffin tissues like

Adrenal medulla and Extra Charoid bodies

postganglionic neuron stimulate _____ which secrete ______

adrenergic neurons

Norepinephrine

Chromaffin tissue in

Post-ganglionic nuerons

secrete norepinephrine

-a neurotransmitter

Chromaffin tissue in

Carotoid bodies

Respond to BP changes

-cause a change in cardiac function

Responds to CO2 and O2

-Causes changes in breathing

Chromaffin tissue in

Paraganglia

of extra-adrenal origin on the two sides of the vertebral column

Large organ of Zuckerkandl

Chromaffin tissue in

paragnaglia- Large organ of Zuckerandl

Source of catecholamines in the fetus

Atrophies at birth

Chromaffin tissue in

Adrenal medulla

Is not neurons here or sympathetic ganglia

Release catecholamines like epinephrine

The adrenal cortex is

stereogenic

Catecholamines from the medulla include

epinephrine

norepinephrine

dopamine

The _______ act on the cortex, which acts on the ______, which secretes the enzyme ______

Glucocorticoids

medulla

Phenylethanolamine-N-methyl Transferase (PNMT)

Sympathetic Nervous System (SNS) is

discrete

a chain of 23 ganglia

from the T1 - L2 vertebrae

The SNS is active during

stress

The celiac ganlion of he SNS is

large and under the sternum

The other ganglion of the SNS include

Superior and inferior ganglion

The parasympathetic nervous system is

Not secrete

The parasympathetic fiber travel via the

cranial nerves (3, 7, 9, 10)

and the

Spinal nerves S2, S3, S4

The cranial and spinal nerves are called the

cranial-sacral divisions of the ANS

Tumors of the chromaffin tissue are called

Pheochromocytomas

The biosynthesis of catecholamines

Tyrosin----->

Dihydroxyphenylamine (DOPA)

The enzyme used is Tyrosine Hydroxylase (RATE LIMITING)

The cofactor used is

Tetrahydrobioplain + O2----> Dihydrobioptren

The biosynthesis of catecholamines

The Rate limiting enzyme is

Tyrosine Hydroxylase

The biosynthesis of catecholamines

Dihydroxyphenylamine (DOPA)---->

Dopamine

The enzyme used is Dopacarboxylase

The biosynthesis of catecholamines

Dopamine--->

Norepinephrine

The enzyme used is Dopamine-β-Hydroxylase

The cofactor used is Ascorbic Acid---> Dehydroascorbic acid

The biosynthesis of catecholamines

Norepinephrine also comes from

Tyrosin----->

Tyramine--->

Octopamine--->

Tyrosine----> Tyramine

The enzyme used is Amino Acid Decarboxylase

Tyramine---> Octopamine

The enzyme used is Dopamine-β-Hydroxylase

Octopamine---> Norepinephrine

The enzyme used is Octopamine Hydroxylase

The biosynthesis of catecholamines

Norepinephrine--->

Epinephrine

The enzyme used is PNMT

The biosynthesis of catecholamines

Epinephrine can also come from

Dopamine---->

Epinine------->

Dopamine----> Epinine

The enzyme used is PNMT

Epinine----> Epinephrine

The enzyme used is Phenylamine Hydroxylase

If you give ____ to someone, it helps Parkinson's

L-Dopa

Tyrosine ----->------>---->

A lot of steps

Melanin

The enzyme used is tyrosinase

Catecholamines are stored as

Granules in the cell

Catecholamines are transported by

being bound to Albumins (10^-7 in size)

Catecholamines are secreted

During stress starvation, hypoglycemia, Hypotension

The ruptake of catecholamines happen by

Na+-T tansporters

The reupatake of catcholamines can be inhibited by

Cocaine, Amphetimaines, Sympathaminetic drugs

Anti-depressents act by

inihibiting MAO and Reuptake blockers

Extra-nueronal uptake of catecholamines happen in the

Salivary Gland

Phenothiazine

Block the D2 receptors

-Prevents Vomitting (Anti-emetic)

-Givent to chemotherapy

Degradation of Catecholamines

Epinephrine---->

Metanephrine

under the enzyme COMT

Degradation of Catecholamines

Norepinephrine ----->

Noremetanephrine

Under the enzyme COMT (Catchol-O-Methyl)

Degradation of Catecholamines

Norephinephrine and ephinephrine can also become

3,4-Di-OH-Mandelic Acid

Under the enzyme MAO(Monoamine oxidase)

Degradation of Catecholamines

Metanephrine--->

Normetanephrine---->

3-methyl, 4-OH-Mandelic Acid (Vanillymandelic acid)

under the enzyme MAO

Degradation of Catecholamines

3,4-Di-OH-Mandelic Acid

3-methyl, 4-OH-Mandelic Acid (Vanillymandelic acid)

Under the enzyme COMT

3-methyl, 4-OH-Mandelic Acid (Vanillymandelic acid)

3-methyl, 4-OH-Mandelic Acid (Vanillymandelic acid) is

excreted by kidneys

Dopamine degredation A

Dopamine---->

Dihydroxy Phenyl Acetic Acid

the enzyme used is MAO

Dopamine degredation A

Dihydroxy Phenyl Acetic Acid----->

Homovanillic acid

The enzyme used is COMT

Dopamine degredation B

Dopamine--->

3-methyloxytyramine

Dopamine degredation B

3-methoxytyramine--->

Homovanillicacid

The enzyme used is MAO

catecholamines are conjucated by _____ via _______ acid

This makes them _____ to be excreted

Sulfication

Glucaronic acid

soluble

Catecholamines act via

andrerginic receptor

-7-span transmembrane domain

-GPCR

Receptors of catecholamines α1

α1 receptors

Dominant post synaptic receptors

-GqPCR

-Cause lipolysis, sweating from the eccrine sweat glands(stress induced)

- Typically M3 receptor

Receptors of catecholamines α1

α1 on smooth musceles

Cause contraction of Urinary bladder, Uretes, Urethra, Bronchoconstriction

Iris Radial muscle

-papillary dilation

Receptors of catecholamines α1

α1 blocker

Pentalamine Phenoxylbenzamine

-Treats Hyper tension

Receptors of catecholamines α1

α1 receptor mechanisms

GqPCR---> acts via phospholipase -----> gives IP3 and DAG from phospholipase------> Activates Protein kinase C(PKC)---> opens Ca2+ channels

Receptors of catecholamines α2

α2 receptor

GiPCR

On the presynaptic receptors act as auto regulators

Ins

Receptors of catecholamines α2

α2 receptor effects

Insulin Secretion- inhibited

Glucagon secretion- stimulate

lipolysis-FFA levels rise

Receptors of catecholamines α2

α2 receptor neurons

NE binds to the α2 cauing a stopage of NE secretion

Receptors of catecholamines α2

α2 receptor blockage

Clonidine is an alpha 2 suppressor

Receptors of catecholamines α2

α2 receptor Clonide suppression test

Give 0.3mg clonide Orally

Measure CA's 3 HRs later

Normal level: <500pg/mL

High levels: >2000pg/mL

Receptors of catecholamines α2

If CA's are high after the Clonide Suppression test then

There is tumor likely

-Phenochromocytomas

Receptors of catecholamines β1

β1 receptor are

GsPCR

Are in the Heart muscles

Induce

Ino-, Chrono-, Lusi- tropic effects

Receptors of catecholamines β1

β1 receptors are blocked by

Propranolol

Cardiomyocyte photo β1

Ca2+ inters via the stimulus of the action potential affecting the ________

This caused the Ca2+ to affect the ____ Receptor which releases more ____ which causes muscle contractions.

Once done the Ca2+ goes back into the SR via the ______ channel

Dihydropyride Receptor (Voltage Gated)

Ryanodine Receptor

Ca2+

SERCA2

Cardiomyocyte Photo with β1 receptors

_____ inhibits the ______ channel causing longer muscle contractions

The binding of NE to the β1 receptor on the membrane causes the activation of the ______ ____.

______ is phosphorylated by the PKA causing no inhibition on the _______

If the SERCA2 isn't inhibited then there is rapid Ca2+ into the cell and fast relaxation of the muscle or a __________ effect on the muscle

phospholamban

SERCA 2

CAMP PKA

phospholamban

SERCA 2

Lusiotropic effect

Receptors of catecholamines β2

β2 receptor are

GsPCRs

CAMP----> PKA which act on the mLcK phosphylation in the active

Receptors of catecholamines β2

β2 receptor causes

relaxation in the smooth muscle

Bronchodilation

Receptors of catecholamines β2

β2 receptor causes vasodilation in

Urinary bladder, Ureter, Urethra, Ureters--->relax

GI tract Sphincters--->relax

Receptors of catecholamines β2

albuterol binds the β2 receptor causing

Ease of breathing

Receptors of catecholamines β2

The PKA of the β2 receptor causes ________ in the _____ ____ ____ ___ (in actin)

this causes contractions.

These contractions can be inhibited by ____ _____

Phosphorylation

Myosin Light Chain Kinase (mLcK)

Rho kinase

Receptors of catecholamines β2

The Phosporylated mLcK alongside a myosin light chain and _____ _______ causes the _______ of the mLcK which causes _____ of the muscle

mLc Phosphatase

unphosphorylation

relaxation

Receptors of Catecholamines β2

In the cardiac muscles, the β2 is ______, and it _____ apoptosis.

It inhibits apoptosis by releasing these factors _____

GiPCR

inhibits

AKT (PKB or Serine/Threonine Protein Kinase)

Phosphoinositide-3-Kinase(PI3-K)

MTOR (Mammalian target of rapanycin)

Receptors of Catecholamines β3

In the _____ ____ this is mutated on the ____ cells which are responsible for insulin release

This causes _______ or the _____ of the brown fat

Pima indians (Arizona region of US)

β cells

Thermogenesis or Lipolysis

Receptors of Catecholamines β3

Act via ___ ___ ___ ___ this causes the _____ or _______of the β-adrenergic receptors

Beta adrenergic receptors kinase (BARK)

Inactivation

Internalization

Receptors of Catecholamines β3

If the BARK is down regulated in causes

The β arrestin to bind and block G-protein of the β-adrenergic receptors

Hypofucntion of catecholamines causes

Autonomic insufficiency

Orthostatin hypotension

causes Low Glucagon-----> hypoglycemia

Hyper function of catecholamines

perspiration and Hypertension

Glucagon test

1mg of glucagon via IV

Then measure CAs after 1 min

Normal levels: <500pg/mL

High levels: >2000pg/mL

High levels of CAs in the glucagon test indicate a

Tumor or pheochromotocytoma

causes hyper function

Adrenal cortex is _____ meanig it produces ____ hormones

Steriodonginic

Mesodermal

The adrenal cortex has a lot of ____ ____ because they are the primary place of steriod hormone production

Smooth ER

Windows in 1928 found

Cholesterol is the precursor for all steroid hormones

In 1935 windows _____ cholesterol for the first time

Crystalized

Windows found that estrogen caused

and estradiol ___

caused symptoms of menopause

prevent the symptoms of menopause

The Zona Glomerulosa comprises ____ of the adrenal cortex and produces __________

15%

mineralcorticoids

The Zona glmerulosa produces ____ and the enzyme _____ it is not under ____ control

Aldosterone

P450 Aldo (Aldosterone synthase)

The Zona fasciculata comprises ___ of the adrenal cortex and produces ______

75%

Gucocorticoids

The Zona fasciculata produces ____ as well as the enzyme ______, it is under ____ control

Cortisol

17α-Hydrolase

ACTH control