Basic Molecular Endocrinology LR Flashcards
Name the properties of water soluble hormones
• Peptides (or derivatives) & proteins
• Water soluble leads to short T1⁄2
• Bind to specific receptors on target
cell membranes
- Alter activity of existing enzymes
inside cell (secs to min) - Activate transcription of new proteins (min to hours)
GPCR
- ligands?
- what is an example of something that uses a GPCR to enter cells?
Variety of ligands – Proteins and peptides – Fatty acid derivatives – nucleotides – Smell/taste, photons – Target of many drug
EPINEPHRINE
– Can activate 9 distinct GPCRs
– Different receptors are expressed by different cell types and elicit
different responses
What about G proteins?
No Ligand bound to receptor
– Inactive G protein
– GDP bound to G protein
Signal binding receptor causes CONFORMATIONAL CHANGE
– Transfer change to G protein > GDP released, GTP binds
- >ACTIVATES G PROTEIN
- Hormone (1st messenger) binds receptor
- Receptor activates G protein
Give an Example of Some GPCR ligands
Epinephrine ACTH FSH LH Glucagon PTH TSH Calcitonin
What happens when G protein is activated?
Required for production of 2nd messengers
Examples of 2nd messengers:
• cAMP, cGMP
• Inositol Triphosphate (IP3),
Diacylglycerol (DAG) • Calcium
What are some examples of second messengers?
Examples of 2nd messengers:
• cAMP, cGMP
• Inositol Triphosphate (IP3),
Diacylglycerol (DAG) • Calcium
Explain the messenger pathway
- Hormone (1st messenger) binds receptor
- Receptor activates G protein
- G protein activates adenylate cyclase
- Adenylate cyclase converts ATP to cAMP (cAMP is 2nd messenger)
- CAMP activates protein kinases (pKA)
By cAMP activating pKA, what does this do?
cAMP mostly activates PKA
PKA phosphorylates specific target proteins.
1. Regulates protein activity – Activates some enzymes – Deactivates some enzymes – Stimulates cellular secretion
- Opens ion channels
What is the liver’s response to epinephrine?
Activates PKA -> which acts on 3 paths
- INHIBITS glycogen synthase (fast)
- ACTIVATES glycogen phosphorylase (fast) –> breakdown of glycogen in liver and muscle
- activates CREB binding protein -> gene transcription (many genes activated/repressed —> ACTIVATES glycogen phosphorylase (mins- hours)
Describe some cell type specific responses to EPNIEPHRINE
• Some responses to epinephrine – Increase blood pressure and heart rate – Increase metabolism • Breakdown of glycogen by liver • Breakdown of fatty acids by adipose – Increase breathing rate
• Relax smooth muscles of the lungs
– Increase blood flow
- Contract smooth muscles around blood vessels
- Some cells don’t respond at all
describe the different response to epinephrine in SKELETAL versus SMOOTH muscle in the LUNG and in BLOOD vessels
*Different intracellular properties or different receptors
. Skeletal muscle mobilises glucose from glycogen
– PKA phosphorylates glycogen phosphorylase
– β2-adrenergic receptor
Smooth muscle of lungs relax, breathe more deeply
– PKA phosphorylates (inactivates) myosin light chain kinase (MLCK)
– MLCK can no longer phosphorylate the myosin regulatory light chain
– No muscle contraction
– β2-adrenergic receptor
• Smooth muscles around blood vessels contracts (α1-adrenergic receptor)
– Increases blood flow
– Leads to Ca2+ released from ER
Adrenergic Rector Class:
B1 receptor
Location
Effect of binding>:
Class : β1
Major location: Predominately heart (also kidney, adipose)
Effect of binding: Increases heart rate and strength
Adrenergic Rector Class:
B2 receptor
Location
Effect of binding>:
Lungs and most other sympathetic target organs; blood vessels serving heart, liver and skeletal muscle
Effects mostly inhibitory; dilates blood vessels and bronchioles; relaxes smooth muscle walls of digestive and urinary visceral organs; relaxes uterus
Adrenergic Rector Class:
beta 3 receptor
Location
Effect of binding>:
Adipose tissue
Stimulates lipolysis
Adrenergic Rector Class:
alpha 1receptor
Location
Effect of binding>:
Blood vessels serving skin, mucosae, abdominal viscera, kidneys and salivary glands; also, all sympathetic target organs except heart
Constricts blood vessels and visceral organ sphincters; pupillary dilation
Adrenergic Rector Class:
alpha 2 receptor
Location
Effect of binding>:
Membrane of adrenergic axon terminals; pancreas; blood platelets
Inhibits NE release from adrenergic terminals; inhibits insulin secretion by pancreas; promotes blood clotting
what does target cell activation depend on?
– Blood concentration of hormone
– Relative number of hormone receptors
– Affinity/strength of binding to receptor
– Proteins present in cell
– Type of receptor
– Other hormones present (synergism, antagonism etc.)
Target cell receptors are dynamic
Target cell receptors are dynamic
– Can increase receptors in response to increase[hormone]
– High hormone levels can decrease receptors (desensitisa
Hormones act as AMPLIFIERS
eg. 1 hormone causes 1000s of second messengers (cAMP) to be activated
What inhibits hormone action
PHOSPHODIESTERASE
Phosphodiesterase inhibitors (e.g. caffeine) Increase cAMP and prolongs hormone action
Summary: What are the cell responses to hormones?
– GPCR pathway activation (transduce signal across PM)
– Use second messenger, amplifies signal
– Pathway must be switched off
– Activates pre-existing proteins and induces production of new
proteins
ONE SIGNAL LEADS TO A TARGET CELL SPECIFIC RESPONSE
– Signals present (synergism, antagonism, concentration, receptor affinity
– Receptor (type, number, affinity)
– Type of second messenger (activated/inhibited)
– Set of effector proteins targeted (what is in cell)
– Activates/represses gene expression (other transcription factors)
What are water soluble hormones?
How long do they take to work?
• Peptides (or derivatives) & proteins
• Most water soluble, short T1⁄2
• Bind to specific receptors on target
cell membranes
Response:
- Activate existing enzymes inside cell (secs to min)
- Activate transcription of new proteins (min to hours)
Describe STEROID & LIPOPHILIC hormones
• Variable structures • Lipid soluble, LONGT1⁄2 • Transported by carrier proteins in blood • Enter target cells and bind intracellular receptor – Cytoplasm or nuclear located
RESPONSES
1. Activate transcription of new proteins (min to hours)

Steroid and Lipophilic Hormones
Steroids & lipophilic hormones
- Steroids are synthesized from cholesterol
- Thyroid hormones (T3 and T4) are synthesized from tyrosine
• All small and lipophilic (must travel in blood with carrier)

