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ENDOCRINOLOGY CAM304 > Basic Molecular Endocrinology LR > Flashcards

Basic Molecular Endocrinology LR Flashcards

1
Q

Name the properties of water soluble hormones

A

• Peptides (or derivatives) & proteins
• Water soluble leads to short T1⁄2
• Bind to specific receptors on target
cell membranes

  1. Alter activity of existing enzymes
    inside cell (secs to min)
  2. Activate transcription of new proteins (min to hours)
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2
Q

GPCR

  • ligands?
  • what is an example of something that uses a GPCR to enter cells?
A 
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

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3
Q

What about G proteins?

A

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

  1. Hormone (1st messenger) binds receptor
  2. Receptor activates G protein
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4
Q

Give an Example of Some GPCR ligands

A 
Epinephrine
ACTH 
FSH
LH
 Glucagon
 PTH
TSH 
Calcitonin
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5
Q

What happens when G protein is activated?

A

Required for production of 2nd messengers

Examples of 2nd messengers:
• cAMP, cGMP
• Inositol Triphosphate (IP3),
Diacylglycerol (DAG) • Calcium

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6
Q

What are some examples of second messengers?

A

Examples of 2nd messengers:
• cAMP, cGMP
• Inositol Triphosphate (IP3),
Diacylglycerol (DAG) • Calcium

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7
Q

Explain the messenger pathway

A
  1. Hormone (1st messenger) binds receptor
  2. Receptor activates G protein
  3. G protein activates adenylate cyclase
  4. Adenylate cyclase converts ATP to cAMP (cAMP is 2nd messenger)
  5. CAMP activates protein kinases (pKA)
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8
Q

By cAMP activating pKA, what does this do?

A

cAMP mostly activates PKA
PKA phosphorylates specific target proteins.

1.
Regulates protein activity
–  Activates some enzymes
–  Deactivates some enzymes
–  Stimulates cellular secretion
  1. Opens ion channels
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9
Q

What is the liver’s response to epinephrine?

A

Activates PKA -> which acts on 3 paths

  1. INHIBITS glycogen synthase (fast)
  2. ACTIVATES glycogen phosphorylase (fast) –> breakdown of glycogen in liver and muscle
  3. activates CREB binding protein -> gene transcription (many genes activated/repressed —> ACTIVATES glycogen phosphorylase (mins- hours)
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10
Q

Describe some cell type specific responses to EPNIEPHRINE

A 
•  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
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11
Q

describe the different response to epinephrine in SKELETAL versus SMOOTH muscle in the LUNG and in BLOOD vessels

A

*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

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12
Q

Adrenergic Rector Class:
B1 receptor

Location
Effect of binding>:

A

Class : β1
Major location: Predominately heart (also kidney, adipose)
Effect of binding: Increases heart rate and strength

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13
Q

Adrenergic Rector Class:
B2 receptor

Location
Effect of binding>:

A

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

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14
Q

Adrenergic Rector Class:
beta 3 receptor

Location
Effect of binding>:

A

Adipose tissue

Stimulates lipolysis

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15
Q

Adrenergic Rector Class:
alpha 1receptor

Location
Effect of binding>:

A

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

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16
Q

Adrenergic Rector Class:
alpha 2 receptor

Location
Effect of binding>:

A

Membrane of adrenergic axon terminals; pancreas; blood platelets

Inhibits NE release from adrenergic terminals; inhibits insulin secretion by pancreas; promotes blood clotting

17
Q

what does target cell activation depend on?

A

– 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.)

18
Q

Target cell receptors are dynamic

A

Target cell receptors are dynamic
– Can increase receptors in response to increase[hormone]
– High hormone levels can decrease receptors (desensitisa

19
Q

Hormones act as AMPLIFIERS

A

eg. 1 hormone causes 1000s of second messengers (cAMP) to be activated

20
Q

What inhibits hormone action

A

PHOSPHODIESTERASE

Phosphodiesterase inhibitors (e.g. caffeine) Increase cAMP and prolongs hormone action

21
Q

Summary: What are the cell responses to hormones?

A

– 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)

22
Q

What are water soluble hormones?

How long do they take to work?

A

• Peptides (or derivatives) & proteins
• Most water soluble, short T1⁄2
• Bind to specific receptors on target
cell membranes

Response:

  1. Activate existing enzymes inside cell (secs to min)
  2. Activate transcription of new proteins (min to hours)
23
Q

Describe STEROID & LIPOPHILIC hormones

A 
•  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)



24
Q

Steroid and Lipophilic Hormones

A

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)



25
Q

What do thyroid hormones do?

A

• Major metabolic hormone
• Increases metabolic rate and heat production (calorigenic effect)
• Regulation of tissue growth & development
– Development of skeletal and nervous systems
– Reproductive capabilities

• Maintenance of blood pressure

26
Q

What are thyroid hormones essential for?

A

Thyroid hormones are essential for cell differentiation, growth and metabolism

27
Q

Explain the pathway for release of thyroid hormone

A

PHYSICAL/emotional stimuli –>Hypothalamus -> TRH -> pituitary gland -> thyroid stimulating hormone -> thyroid -> t3/4 release

28
Q

explain iodide uptak enad storage

A

Idodide uptake is rate limiting step-
TSH sensitive ion pump oxidised
• iodide → iodine
• Incorporate iodine into TG (thyroglobulin )tyrosine residue

– 8-10 out of 40 total processed
• Stored i n high concentration

29
Q

Explain the process of T3/T4 release

A

to release thyroid hormone- process responsive to thyroid stimulating hormone
need to be endocytosed, go in cell in droplets, protein needs to be broken down to
release hormones in cell.
use proteases and lysosomes to help degrade- release of T3 and T4 which are
released from cell. 90% in the form of T4, 10% in the form of T3.
any iodine attached to thyroid hormone is recycled- taken back into cell,
taken outside, retrapped in thryoglobulin protein to be reused

30
Q

How do T3/4 travel in blood to target cells?

A

Most transported on plasma proteins, small amount “free”
• Plasma protein transport extends biological life (days in plasma)
• ~ 1 week supply in plasma and 2-3 month supply in follicle colloid
• Unbound ‘free’ hormone is biologically active (rapid release)

31
Q

T4 and 3 properties

A

• Freely cross membranes
• T4 has a longer half-life than T3
– In plasma about 20 X more T4 than T3
– T4 is gradually converted to T3 within cells

T3 is BIOLOGICALLY ACTIVE FORM

32
Q

THYROID hormones increase the metabolism of ALL cells, but DIFFERENTLY:
what do they do in mitochondira?
What hormones does it enhance?

A

↑ ATP production by mitochrondria
↑ Basal metabolic rate (O2 consumption)
↑ Fuel metabolism (CHO, fats, AAs)
↑ Heat production (“calorigenic effect

33
Q

OUTLINE the DIFFERENCES between
1- WATER SOLUBLE HORMONES
2- LIPID HORMONES

A

• CELL REPSONSE TO WATER SOLUBLE HORMONES
– GPCR pathway activation (transduce signal across PM)
– Use second messenger, amplifies signal
– Pathway must be switched off
– ACTIVATES/DEACTIVATES pre-existing proteins and activates
transcription of new proteins (hormone-responsive)

CELL RESPONSES TO LIPOPHILIC HORMONES
– Crosses PM, binds intracellular receptor
– No second messenger or amplification of signal
– Activates transcription of hormone-responsive genes

ONE SIGNAL LEADS TO A TARGET CELL SPECIFIC RESPONSE

ENDOCRINOLOGY CAM304 (8 decks)

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