Biochem 1: hormone action Flashcards
Where are endocrine hormones secreted into
the blood
True or False: endocrine hormones travel to distant sights of action
True
What is an endocrine hormone
chemical secreted by cell or group of cells into the blood
What are the general characteristics of endocrine hormones
- work on multiple tissues
- work at relatively low concentrations
- Have to bind to receptors on either cell surfaces or intracelluar
- Ellicit non-genomic or genomic responses
What are the 2 major classes of hormone receptors
- cell surface receptor
2. intracellular receptor
Intracellular receptors can be subdivided into 2 types, what are they
- cytosolic
2. nuclear
What do hormonal responses depend on?
- R availability
- hormone concentration
- affinity for the receptor
What happens with cytosolic receptors
translocates to the nucleus after binding of ligand
What happens with nuclear receptors
since its already in teh nucleus, it is directly associated with DNA and gene they are regulating
cell surface receptors lead to…
and how do they do it
rapid, non genomic responses
by altering protein functions
however, can have genomic response BUT often occurs through a CASCADE EFFECT
Intracellular receptors lead to…
and how do they do it
delayed, genomic responses
by altering gene expression
How many transcription factors domains are associated with intracellular steroid receptor
4
DNA binding domain ligand biding domain Dimerization domain Trans-activation domain (cytosolic only) nuclear localization signal
What is the DNA binding domain
- binds the receptor/ligand complex to the DNA sequence needed to regulate the gene of interest
What are also seen in the DNA binding domain
Zinc fingers - allows for binding to DNA in proper oreintation
so that the TF’s can bind the recptor complex and regulate gene expression
What is the Ligand binding domain
the portion of the receptor that binds the hormone
What is the dimerization domain
allows for the dimerization of receptor/ligand complex
Dimerization is often needed for…
the correct function of TF/R complexes
TRUE or FALSE : is dimerization domain seen in all steroid receptors
FALSE
What is the trans-activation domain
portion that binds to transcriptional regualtor proteins
What is the nuclear localization signal
allows for the targeting of the ligand/receptor complex to the NUCLEUS
Where are the sites of hormone production in the Endocrine system
- hypothalamus and pituitary gland
- thyroid and parathyroid
- adrenal
- pancreas
- ovaries and testes
What are the 3 main categories of hormones based on chemical classification
- protein/peptide
- steriod
- amino acid
What are the 3 main categories of hormones based on chemical classification
- protein/peptide
- steriod
- amino acid
what are protein/peptide made from
gene expression of protein expressing genes (In other words they are made of Proteins)
The majority of hormones are (BLANK) hormones
protein/peptide
especially those from the pituitary
what are protein/peptide made from
gene expression of protein expressing genes
The majority of hormones are (BLANK) hormones
protein/peptide
especially those from the pituitary
Are protein/peptide hormones water soluble or insoluble
soluble
TRUE or FALSE: protein/peptide hormones have a quick half-life
TRUE; minutes
Which receptors do they usually bind to
cell surface receptors
and leads to rapid response
channels, enzymes, transport can be altered by which hormone
protein/peptide
protein/peptide hormone response is dependent on what 3 facotrs?
- hormone concentration
- availability
- affinity of receptor for ligand
can protein hormones be made in advanced? why?
yes, bc they can be stored in vesicles and released when needed
What is the first step in synthesizing protein/peptide hormone
pre-prohormone is made in the RER
how is pre-prohormone made
mRNA on ribosome binds aa into a peptide chain
What happens to pre-prohormone
its modified in the ER to PROHORMONE due to removal of a signal sequence, which makes it inactive
Where do the prohormones go to next
goes through the Golgi complex
after the golgi, what happens to the prohormone
secretory vesicles bud off the golgi containing prohormone and enzymes
the enzymes cut the prohormone in active peptides (hormone)
how are peptide hormones secreted
vesicles fuses with cell membrane which releases the hormone into the blood
where do steroid hormones derive from
cholesterol
Are steroid hormones water soluble or lipid soluble
lipid soluble
How do they enter the cell
via diffusion
What is the half-life of steroids
usually hours
they have long half-lives
Why do steroid hormones typically have long half-lives
bc they bind to plasma protein (Albumin) –> leads to ‘reserve pool’
steroids attached to proteins are NOT CLEARED from the blood readily
Steroid receptors bind to which receptor
intracellular receptor
What do steroid hormones act on once inside the nucleus
Chromatin (as TF) ; regulating gene expression
steroid hormone lead to delayed, genomic response; true or false
TRUE
how are steroid hormones usually secreted as
pre-prohormone, which have to be cleaved to an active hormone
Can steroid hormones be stored in vesicles, why?
no they can’t bc they are lipophilic so they would seep out
therefore
made as needed
where are steroid hormones made
adrenal cortex, gonads, placenta
What two hormones classes are Tyr based
Thyroid and Catecholamines
What hormones are made in the gonads
estradiol and other sex hormones
what are the some thyroid hormone properties
long half-life
nuclear hormones –> act on chromatin
What two hormones are Tyr based
Thyroid and Catecholamines
what hormone is Trp based
Melatonin
what are the some thyroid hormone properties
long half-life
nuclear hormones –> act on chromatin
name 2 thyroid hormones
Thyroxine (T4)
Triiodothyronine (T3)
name 3 Catecholamines
dopamine, NE, Epi
what are the some Catecholamine properties
neurohormones
short half life
acts on cell surface receptors
what is short neg feedback
the ant. pituitary hormone feeds back on the hypothalamus to inhibit secretion of hypothalamic-releasing hormone
e.g: GH inhibits GHRH
what is long neg feedback
from the gland the hormone feeds back all the way to the hypothalamic-pit axis
e.g: insulin-like growth factor 1 (IGF-1) is stimulated to be released by GH. IGF-1, in turn, inhibits GHRH and GH
what is ultrashort neg feedback
hypothalamic hormone inhibits its own secretion
e.g: GHRH inhibits GHRH secretion
what is short neg feedback
the ant. pituitary hormone feeds back on the hypothalamus to inhibit secretion of hypothalamic-releasing hormone
what is long neg feedback
from the gland the hormone feeds back all the way to the hypothalamic-pit axis
what does positive feedback do
product stimulated by hormone release –> eventually cause an increase in hormone release
enhance stimulus
culminates in events
Give an example of positive feedback
oxytocin during labor
culminates in childbirth
Give examples of negative feedback
EPO, ANP, aldosterone, ADH/AVP, insulin, leptin
What is regulated in peptide hormones
BOTH synthesis and release
Are steroid hormone synthesis regulated? release?
yes synthesis is regulated
no release isn’t bc no storage of steroid hormone
What is regulated in amino acid hormones
only synthesis
( She put that in her slide, but catecholamines are always put into vesicles and then released upon proper stimulus, not entirely sure if she made a mistake or not).
the intended response element will inhibit hormone release, is what type of feedback mech?
simple
Example of simple feedback
glucagon is released in response of low blood sugar. The release then stimulates an increase in blood sugar. Then the increased sugar level causes inhibition of glucagon release
what are the major signaling pathways
- intracellular receptors
- jak/stat
- GPCR
- PI-3 Kinase pathway
- RAS pathway
What are the properties of intracellular receptors
they are inside the cell and have hydrophobic ligands
they act in the nucleus by binding to DNA –> regulating genes
have delayed, genomic response
name some hydrophobic ligands
Vit D3, cortisol, aldosterone, estrogen
jak/stat is a membrane spanning receptor; true or false
TRUE
which ligands bind to jak/stat
prolactin, GH
Does STAT activate JAK
NOPE!
JAK activates STAT
what does STAT do
translocates to the nucleus after being activated by JAK and regulates gene expression
STAT
Signal Transducer and Activator of Transcription
JAK
Janus Kinase
Are GPCR a membrance spanning receptor
yes, they bind to ligands at the cell membrane
What 3 variants do GPCR activate
Gs, Gq, Gi
How does Gs work
activate adenlyl cyclase –> producing cAMP –>activates PKA –> phosphorylate effector molecules either inhibiting it or activating it
what hormones works on Gs
Epinephrine (among other, ADH does as well for V2 receptors)
Gs has only cellular effects; TRUE or FALSE
FALSE
they have both cellular and genomic effects (through CREB)
What does Gi do
inhibits Gs
What does Gq do
activates PLC –> PLC will cleave membrane lipids to DAG and IP3 –> leads to an increase in Ca2+ –> activates PKC –> phosphorylate effector molecules
Gq only has genomic effects; TRUE or FALSE
FALSE, sucka
they have both cellular and genomic effects (through CREB)
How does PI-3 kinase work
tyrosine kinase (TK) activates PI3 –> activates PKB
what kind of effect does PKB have
genomic effect
what hormone binds to PI-3 kinase
insulin
How does RAS pathway work
TK activates RAF –> activates MEK –> activates ERK –> ERK translocates to the nucleus and has genomic effects
What disorder is associated with hyposecretion
DM1
Cushings is associated with…
Hypersecretion (too much cortisol)
what disorder is associated with abnl tissue respsonse
DM2
