Lecture 58-Mechanism Of Hormone Action And Second Messengers Flashcards
The final outcome of interaction of hormone and target cells depends on …. (5 things)
- Hormone concentration
- Receptor number
- Affinity of hormone for receptor
- Duration of exposure to hormone
- Intracellular factors—enzymes, cofactors
What is hormone responsiveness expressed as?
Dose-response relationship
As concentration of hormone increases, response ______ and then _______.
Increases
Levels off
More receptors on a target tissue, ______ maximal response.
Increases
What is the maximum response in hormone action?
A further increase in hormone will elicit no more response
What is a decrease in responsiveness caused by?
-decrease in number target cells or total receptors/cells
-decrease concentration of enzymes activated by hormone
What are two ways that sensitivity can be changed in a hormone?
Changing number of receptors
Changing affinity of receptors
If more hormone is required to get _____ response, then the sensitivity goes _____.
50%
Down
Decreasing sensitivity = _____-_____ of receptors
Down-regulation
What will happen to the number or affinity of receptors, even when hormone concentration is high?
Decrease
Increasing sensitivity = ___-____ of receptors
Up-regulation
When either number or affinity of receptors increases, what happens to synthesis and degradation?
Increase synthesis of new receptors
decrease degradation of existing
Activate receptors!
What is the general mechanism of hormone action?
- Hormone is recognized and binds to membrane receptor -> hormone receptor complex
- Hormone-receptor complex EITHER coupled to a signal-generating mechanism OR must act as one
- Generated signal (second messenger) affects intracellular process by altering activity OR concentration of functional or structural proteins
Where are hormone receptor systems located? Which has a faster response?
Cell membrane (Faster response)
Within the cell, cytoplasm or nucleus (slower response)
How does the classic cell membrane receptor system work?
-classified according to membrane receptor structure OR second messenger system
-usually a rapid response (minutes)
How does the catalytic cell membrane receptor system work?
-doesnt use second messenger system, but rather an enzyme system such as kinases
-usually a rapid response (minutes)
How does intracellular receptor system work?
-uses cytoplasmic or nuclear receptors
-usually a slow response (hours
What coupling molecule is used in ALMOST ALL membrane receptor systems?
G-proteins
What are two second messengers?
CAMP
IP3/Ca2+
Which second messenger is Adenylyl Cyclase linked to?
CAMP
Which second messenger is phospholipase C linked to?
IP3/Ca2+
What does cAMP produce and activate?
Protein kinase A
What are intracellular proteins phosphorylation by?
Protein kinase A
What is 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 physiological actions
- Phosphodiesterase degrades cAMP, shutting down system
(TRUE/FALSE) Hormones only use one hormone receptor system
FALSE
Some hormones use multiple hormone receptor systems
Which hormones use the Adenylyl cyclase system?
CRH/ACTH
FSH, LH
TSH
ADH
Calcitonin
PTH
Glucagon
What does phospholipase C liberate?
DAG (diacylglycerol) and IP3 from PIP2
What does IP3 cause release of?
Ca2+
What do Ca2+ and DAG activate?
Protein kinase C
What are the steps of phospholipase C system?
- Hormone binds receptor coupled by a G protein
- GTP binds G protein and activates phospholipase C
- Phospholipase C liberates DAG and IP3 from PIP2
- IP3 causes Ca2+ release from ER or SR stores
- Ca2+ and DAG activates protein kinase C, which phosphorylation proteins
What hormones use the phospholipase C system?
GnRH (gonadotropin-releasing hormone)
TRH (thrytropin-releasing hormone)
GHRH (growth hormone-releasing hormone)
Angiotensin II
ADH
Oxytocin
What are catalytic receptors on the cell surface associated with?
Enzymes on intracellular side
What are two additional compounds that use the guanylyl cyclase enzyme system?
Atrial natriurectic peptide (ANP)
Nitric oxide (NO)
Describe the guanylyl cyclase enzyme system
GTP -> cGMP -> cGMP-dependent kinase -> phosphorylation proteins
What do serine/threonine kinase enzymes need to phosphorylate serine and threonine?
Protein kinase A or C
Ca2+ calmodulin dependent protein kinase (CaMK)
Mitogen-activated protein kinases (MAPK)
What are hormones that utilize intracellular receptor systems?
Glucocorticoids
Sex hormones (estrogen, testosterone, progesterone)
Aldosterone
Vitamin D
Thyroid hormones
Which receptors do steroids use in intracellular receptor systems?
Cytosolic or nuclear receptors
What are the three steps in steroid intracellular receptor systems?
- Steroid hormone diffuses across membrane and binds receptor in cytosol or nucleus
- Receptor undergoes conformational change, complex dimerizes and binds to SRE
- Complex is transcription factor—mRNA is transcribed, translation occurs, new proteins! Slay!
How are tyrosine kinase-associated receptors defined?
Associate with other proteins that have tyrosine kinase activity—Janus kinase family
*intracellular portion cannot phosphorylate itself
What are monomer vs dimer types? (Receptor tyrosine kinases)
Monomer-> receptor dimerizes after hormone binds—tyrosine kinase is activated and phosphorylated tyrosine on itself
Dimer-> receptor already a dimer (insulin and IGF)
What are the three domains a receptor has?
- Extracellular domain for binding the hormone
- Transmembrane domain
3 .intracellular domain -> where tyrosine kinase activity occurs
What is so COOL about receptor tyrosine kinases?
Tyrosine kinase activity occurs WITHIN the receptor itself
*when hormone binds, intracellular portion of receptor phosphorylated itself
