Mechanism of Hormone Action and Second Messengers Flashcards
What is threshold response?
minimal concentration of hormone needed to elicit measurable response
The final outcome of interaction of hormone on cells depends on several factors. List them.
- hormone concentration
- receptor number
- affinity of hormone for receptor
- duration of exposure to hormone
- intraceullar factors such as enzymes and cofactors
Hormone action responsiveness is expressed as?
a dose-response relationship
What does maximum response mean?
a further increase in hormone will elicit no more response
The magnitude of a response is correlated with what?
hormone concentration
What is expressed as the concentration of the hormone that produces half-max response?
sensitivity
Alterations in dose-response curve results from changes in what?
max responsiveness, sensitivity, or both
A decrease in responsiveness can be caused by what?
decrease in number of target cells or total receptors/cell, or concentration of enzymes activated by hormone
In what two ways can sensitivity be changed?
- changing number of receptors
OR - affinity of receptors
Define sensitivity.
The concentration of hormone producing 50% of maximal response
Down regulation of receptors does what to sensitivity?
decreases it
Up regulation of receptors does what to sensitivity?
increases it
What is down regulation of receptors?
either number or affinity of receptors decreases even when hormone concentrations is high
What is up regulation of receptors?
either number other than affinity of receptors increases
What is the general mechanism of hormone action?
- hormone is recognized and binds to a membrane receptor –> hormone receptor complex
- hormone receptor complex EITHER coupled to a signal generating mechanism OR must act as one itself
- generated signal (second messenger) affects intracellular process by altering activity OR concentration of functional or structural proteins
Hormone receptor systems are where?
either on cell membrane or within the cell
What receptor system is classified according to membrane receptor structure OR second messenger system used, and usually incurs a rapid response?
Classic cell membrane receptor systems
What receptor system does not use a second messenger system, but rather an enzyme system such as kinases, and usually incurs a rapid response?
catalytic cell membrane receptor systems
What receptor system uses cytoplasmic or nuclear receptors, and usually incurs a slow reponse?
intracellular receptor systems
What hormones use the adenylyl cyclase system?
- Corticotropin releasing hormone/adrenocorticotropic hormone
- follicle-stimulating hormone, luteinizing hormone
- thyroid-stimulating hormone
- antidiuretic hormone
- calcitonin
- parathyroid hormone
- glucagon
Can hormones use multiple hormone receptor systems?
Yes, some do
What hormones use the phospholipase C system?
- gonadotropin-releasing hormone
- thyrotropin-releasing hormone
- growth hormone-releasing hormone
- angiotensin II
- antidiuretic hormone
- oxytocin
Describe the steps of the adenylyl cyclase system.
- hormone binds receptor coupled by a G protein
- GTP binds G protein and activates adenylyl cyclase
- cAMP produced and activates protein kinase A
- intracellular proteins phosphorylated by protein kinase A, causing physiologic actions
- phosphodiesterase degrades cAMP, shutting down system
Describe the steps of the phospholipase C system.
- hormone binds receptor coupled by G protein
- GTP binds G protein and activates phospholipase C
- phospholipase C liberates diacylglycerol (DAG) and IP3 from PIP2
- IP3 causes Ca2+ release from ER or SR stores
- Ca2+ and DAG activate protein kinase C, which phosphorylates proteins
What hormones utilize the intracellular receptor systems?
- glucocorticoids
- sex hormones (estrogen, testosterone, progesterone)
- aldosterone
- vitamin D
- thyroid hormones
What receptor system uses either cytosolic or nuclear receptors?
intracellular receptor systems
Describe the steps of the intracellular receptor system.
- steroid hormone diffuses across membrane and binds receptor in cytosol or nucleus
- receptor undergoes conformational change, complex dimerizes and binds to steroid responsive elements
- complex is now a transcription factor – mRNA transcribed, translation occurs, new proteins, physiologic action
Cell membrane receptor systems are linked to what?
one of two second messenger systems
Almost all cell membrane receptor systems use what as coupling molecules?
G proteins
G proteins are active when what is bound?
GTP
G protins are inactive when what is bound?
GDP
True or false: G proteins can be inhibitory or stimulatory.
True
In catalytic receptor systems, catalytic receptors on cell surface are associated with what?
enzymes on intracellular side
Describe the guanylyl cyclase enzyme system of catalytic receptor systems.
GTP –> cGMP –> cGMP-dependent kinase –> phosphorylates proteins
Atrial natriuretic peptide and nitric oxide use what enzyme system?
Guanylyl enzyme system
Describe the serine/threonine kinase enzyme system of catalytic receptor systems.
use either protein kinase A or C, as well as Ca2+-calmodulin-dependent protein kinase and mitogen-activated protein kinases to phosphorylate serine and threonine
For receptor tyrosine kinases in catalytic receptor systems, tyrosine kinase activity lies where?
within the receptor itself
Since the tyrosine kinase activity lies within the receptor itself, when the hormone binds what occurs?
intracellular portion of receptor phosphorylates itself
Tyrosine kinase-associated receptors associate with other proteins that have what?
tyrosine kinase activity
Can the intraceullar portion of tyrosine kinase-associated receptors phosphorylate itself?
No, only true receptor tyrosine kinases
