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Endo > Hormones and cell signalling > Flashcards

Hormones and cell signalling Flashcards

1
Q

Define autocrine signalling

A

Affects cell producing the hormone i.e. feeds back on self e.g. growth factors

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2
Q

Define paracrine signalling

A

Diffuses short distances to affect cells nearby e.g. neurotransmitters

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3
Q

Define endocrine signalling

A

Acts on target cells disant from site of synthesis e.g. hormones

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4
Q

Describe the functions of autocrine signalling

A
  • Most effective when performed simultaneously by neighbouring cells of same type
  • Encourages large groups of identical cells to make same developmental decisions
  • For this to work, adjecent cells must have the receptor required in order for signal amplification to occur
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5
Q

What are the consequences of signalling?

A
  • Signal to survive
  • Divide
  • Differentiate
  • Cell death
  • Carry out specialised function
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6
Q

Compare lipid and water soluble hormones

A
  • Lipid: require proteins for transport, bind to intracellular receptors
  • Water: move freely through blood, bind to extracellular receptors
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7
Q

Compare cytokines and growth factors

A
  • Growth factors: polypeptides that promote cell growth/proliferation
  • Cytokines: factors associated with blood cells
  • But no absolute distinction
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8
Q

What is the function of growth factors and cytokines?

A
  • Control fundamental processes
  • E.g. cell division (proliferation)
  • Cell differentiation
  • Apoptosis
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9
Q

Describe lipid soluble hormones

A
  • Not soluble in blood
  • Transported in blood by carrier proteins
  • Diffuse through palsma memrbae
  • Bind to intracellular protein, taken to site of action
  • Alters expression of genes at level of nucleus
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10
Q

Give examples of lipid soluble hormones

A
  • Steroid hormones
  • Androgens
  • Aldosterone
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11
Q

Outline the steps required in order for lipid soluble horones to initiate their action

A
  • Bind to receptors
  • Induce receptor shape change
  • Bind to specific portion of DNA
  • Regulate transcription of that part of DNA
  • Increase or decrease
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12
Q

Desribe lipid soluble hormone receptors

A
  • All structurally related, part of nuclear receptor superfamily
  • Bind to DNA as homo or heterodimers
  • Short DNA binding domain with zinc finger
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13
Q

What are the regions of lipid-soluble hormone receptors?

A
  • Transcription-activating domain
  • DNA binding domain
  • Hormone binding domain
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14
Q

Describe the activation of the lipid-hormone receptor

A
  • In inactive state, bound to inhibitory proteins
  • Binding of ligand causes inhbitory proteins to dissociate
  • Coactivator proteins bind to receptor’s transcription-activating domain
  • Increases gene transcription
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15
Q

Describe water-soluble hormones

A
  • Easily travel in blood
  • Bind to cell surface receptors
  • Initiate intracellular cascade
  • Results in series of intracellular events
  • may be inhibitory or stimulatory
  • Induce signal transduction pathways involving variety of molecules
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16
Q

List the intracellular signal transduction pathways triggered by water soluble hormones

A
  • Adenyl cyclase (cyclic AMP)
  • Guanyl cyclase (cyclic GMP)
  • Phospholipase C, IP3 and DAG
  • Tyrosine kinase
  • Ion channels
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17
Q

What are the possible effects of water-soluble hormones binding to receptor protein?

A
  • Cellular metabolism can change
  • Proteins affecting gene expression altered
  • Amount or location of cytoskeleton altered
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18
Q

What hormones does adenyl cyclase respond to?

A
  • ACTH
  • ADH
  • FSH
  • LH
  • TSH
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19
Q

What hormones does guanylyl cyclase response to?

A

ANP (is rare)

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20
Q

What hormones does phospholipase C respond to?

A

Hypothalamic hormones TRH and GnRH

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21
Q

What hormones does tyrosine kinase respond to?

A
  • Insulin
  • Prolactin
  • Growth hormone
  • IGF
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22
Q

What hormones do ion channels respond to with respect to second messenger signalling of water-soluble hormones?

A

Hormones using multiple pathways

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23
Q

Give an overview of the intracellular signalling pathway for water soluble hormones

A
  • Signal molecule binds to receptor protein
  • Binding leads to change in shape, conveys change in structure through transmembrane domain to intracellular domain
  • Triggers effects in cell
  • Activates intracellular signalling pathway
  • Mediated by series of signalling proteins
  • One or more of these interacts with target protein
  • Alters target protein so helps change behaviour of cell
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24
Q

What are the 3 components of membrane receptors?

A
  • External domain (binds ligand/hormone)
  • Transmembrane domain
  • Cytoplasmic/intracellular domain
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25
Q

What domain of the membrane receptor changes shape to convey the signal?

A

Intracellular (through action of transmembrane domain, passing signal from extra to intracellular)

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26
Q

What is the effect of the conformational change of the intracellular domain of the membrane receptor?

A
  • Stimulates signalling pathway
  • Usually activation of dormant enzymatic activity, often protein kinase
  • Receptor phosphorylates intracellular proteins to further signal transduction
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27
Q

What is the advantage of the intracellular signalling pathways?

A
  • Different hormones act on different receptors
  • Having different signalling pathways that integrate on a few points allows generation of a response that will be most advantagous i.e. one of the 4 basic outcomes
  • The aim is to integrate different signals simultaneously
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28
Q

Describe the receptors for growth factors

A
  • Have enzyme activity
  • Tyrosine kinase
  • Initiate signal that is propagated through cell by phosphorylation
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29
Q

Explain how the same signal can have different effects in different tissues/cells

A
  • Bind to similar receptors
  • Intracellular signals produced interpreted differently
  • E.g. in heart Ach reduces rate and force of contraction, in salivary glands stimulates secretion and in skeletal muscle cell stimulates contraction
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30
Q

Define half life

A

Teh time taken for the concentration of a signalling molecule to fal by half

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31
Q

What factors determine the hald life of a signalling molecule?

A
  • Rate of destruction or removal of molecules

- Turnover rate (which depends on promptness of response when signal turned on)

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32
Q

Compare the half life of molecules that take a long time to synthesise vs molecules that take a short time to synthesise

A
  • Long: long half life

- Short: short half life

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33
Q

What are the 4 main classes of cell surface receptors?

A
  • Ion-channel-linked receptors
  • G-protein linked
  • Tyrosin kinase linked
  • Receptors with intrinsic enzymatic activity
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34
Q

What are ion-channel-linked receptors usually used for?

A

Rapid synaptic signalling e.g.post-synaptic membranes, neuromuscular junction, nicotinic acetylcholine receptor, GABA receptors

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35
Q

Describe how ion-channel-linked receptors work

A
  • Signal molecule (NT) binds to receptor
  • Opens (or closes) ion channel (change in conformation)
  • Ions move into cell by passive diffusion
  • Excitability of post-synaptic cell altered
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36
Q

Describe the structure of G-protein coupled receptors

A
  • 7 transmembrane receptor
  • Single polypeptide chain with central hydrophobic region
  • Spans plasma membrane 7 times, 7 loops
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37
Q

Explain how G-protein linked receptors work

A
  • When ligand binds to 7 transmembrane receptor, changes shape of intracellular loop
  • Allows recruitment and activation of G protein
  • This activates enzyme
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38
Q

What is a G protein?

A

Guanine nucleotide binding protein (signal transduction protein). Composed of 3 different proteins

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39
Q

Explain how G proteins are activated

A
  • Ligand binding to receptor recruits G protein to loop
  • GTP replaces GDP causing protein to dissociate into 2 units
  • End up with 2 activated pathways: G-alpha and G-beta
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40
Q

Outline the types of actions G proteins can have on adenylate cyclase and how

A
  • Can activate or inhibit

- Speciaised proteins (Stimulatory or Inhibitory) and interaction depending on which receptor is activated

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41
Q

Describe the process of stimulatory effects mediated by the adenylate cyclase system and give an example

A
  • Sub-uit of G protein activates adenylate cyclase
  • ATP converted to cAMP catalysed by adenylate cyclase
  • cAMP activates protein kinase A
  • pKa is part of cascade of intracellular phosphorylations
  • Epinephrine acting through adrenergic-B-receptor
42
Q

Describe signal amplification as a feature of the adenylate cyclase system

A
  • Single hormone molecule can result in production of many molecules of cAMP
  • Very efficient means of amplifying receptor hormone interation and original signal
43
Q

How can G proteins be inhibitory? Give an example

A
  • Inhibit adenylate cyclase
  • Thus prevent conversion of ATP to cAMP
  • E.g. norepinephrine acting through alpha-2 receptor on pre-synaptic nerve
44
Q

What are the 2 types of enzyme-linked receptors?

A
  • Function directly as enzymes

- Directly associated with enzymes they activate

45
Q

Describe how the tyrosine-kinase linked receptors work

A
  • Ligands bind, cross-linking
  • Tyrosine residues on intracellular portion of receptor
  • Tyrosine kinase activated when ligand binds
  • Causes phosphorylation of tyrosine residues
  • Phosphate groups act as docking sites for the signalling proteins to bind to
46
Q

What are the different signal transduction pathways from tyrosine kinase receptors?

A
  • Ras signal transduction pathway
  • Phosphoionositide 3-kinase (PI 3-kinase) pathway
  • Phospholipase C
47
Q

What signalling trasnduction pathway is used by insulin?

A
  • Tyrosine-kinase-linked receptor

- Phosphoionositide 3-kinase (PI 3-kinase) transduction pathway

48
Q

What are second messengers?

A

Small intracellular signalling molecules, used to confer signal through cell

49
Q

What are the functions of second messengers?

A
  • Amplify signal
  • Scaffolds
  • relays
  • Adaptors
  • Modulators
50
Q

How do second messengers carry out their functions?

A

Bind to and alter the behaviour of larger intracellular proteins

51
Q

What are the key processes in cell signalling?

A
  • Protein phosphorylation

- Reversal of protein phosphorylation

52
Q

What are enzymes called that act to phosphorylate proteins?

A

Protein kinases

53
Q

What are enzymes called that act to dephosphorylate proteins?

A

Phosphoprotein phosphatases

54
Q

What are the 2 types of protein phosphorylation?

A
  • Phosphorylation of serine/threonine residues

- Phosphorylation of tyrosine residues

55
Q

What on the amino acids is phosphate added to in phosphorylation?

A

Hydroxyl group

56
Q

Name the 6 classes of enzyme linked receptors

A
  • Receptor tyrosine kinases
  • Tyrosine-kinase associated receptors
  • Receptor-like tyrosine phosphatases
  • Receptor serine/threonine kinases
  • Receptor guanyl cyclases
  • Histidine-kinase-associated receptors
57
Q

Compare receptor tyrosine kinases and tyrosine-kinase associated receptors

A
  • RTKs: phosphorylate tyrosines on intracellular signalling molecules
  • Associated: associate with intracellular proteins with tyrosine kinase activity
58
Q

Describe how receptor-like tyrosine phosphatases work

A

Remove phosphate groups from tyrosine on intracellular proteins

59
Q

Describe how receptor serine/threonine kinases work

A

Phosphorylate serines or threonines on regulatory proteins

60
Q

Describe how receptor guanyl cyclases work

A

Catalyse production of cytosolic cGMP

61
Q

Describe how histidine-kinase-associated receptors work

A
  • 2 component system

- Kinase phosphorylates itself and passes on phosphate to intracellular signalling protein

62
Q

What is the function of intracellular molecular switches?

A
  • Required to turn proteins and signals from activate to inactive and vice versa
  • Signalling pathway must receover when not needed
63
Q

How do molecular switches work and what are the 2 main classes?

A
  • Gain or loss of phosphate groups

- 2 classes: phosphorylation or GTP binding

64
Q

Desribe the phosphorylation/dephosphorylation molecular switches

A
  • Signalling protein activated by addition of phosphate and inactivated by removal or vice versa
  • Kinases add, phosphatases remove
65
Q

Describe the GTP binding molecular switch mechanism

A
  • When GDP bound, protein inactive
  • When signal in, GDP exchanged for GTP to activated
  • When signal out, dephosphorylation of GTP and so inactivated again as GDP bound again
66
Q

How can cells adjust their sensitivity to a signal?

A
  • Cell response proportional to the signal
  • Response may depend on binding of more than one intracellular molecule to a target molecule
  • Modulation of receptor activity and density
67
Q

Give the types of target cell desensitisation

A
  • Receptor sequestration
  • Receptor down-regulation
  • Receptor inactivation
  • Inactivation of signalling protein
  • Production of inhibitory protein
68
Q

Describe receptor sequestration

A

Ligand binding to cell-surface receptor induces their endocytosis and temporary storage within an endosome (sequestion)

69
Q

Describe receptor down-regulation in target cell desensitisation to a target molecule

A
  • Ligand binds to receptor, induces their endocytosis

- Receptor destroyed in lysosome

70
Q

Describe the methods of desensitisation of a target cell involving phosphorylation

A
  • 2 ways
  • Either phosphorylate receptor and temprarily silence intracellular domain
  • Change protein involved in transducing signal
71
Q

How does the production of inhibitors desensitise target cells to signal molecules?

A

Blocks transduction process

72
Q

What are the 3 classifications of hormones?

A
  • Classical (genuine) hormones
  • Neurohormones
  • Local hormones
73
Q

Describe the classical hormones

A
  • Secreted by endocrine cells
  • Diffuse into blood
  • Transported by transporters via blood to target tissue
  • e.g. cortisol
74
Q

Describe neurohoromones

A
  • Synthesised by neuroendocrine cells
  • Secreted from nerve terminals
  • Diffuse into blood vessels and transported
  • E.g. Corticotropin-releasing hormone (CRH)
75
Q

Describe local hormones

A
  • Diffusion of hormone into interstitial fluid

- Paracrine function and autocrine function

76
Q

What are the different types of transport proteins for lipid soluble hormones?

A
  • Specific globulins

- Non-specific

77
Q

Give examples of specific globulins

A
  • Cortisol binding protein/globulin (CBG)
  • Vitamin D binding globulin
  • Thyroid binding globulin
78
Q

Give examples of non-specific transport proteins

A
  • Albumin (steroids)

- Pre-albumin (T3 and T4)

79
Q

Where are transport proteins produced and degraded?

A

In the liver

80
Q

What does total hormone concentration measure?

A

Bound and free (active) hormone

81
Q

What is the amount of free hormone affected by?

A
  • The binding protein concentration

- Hormone level

82
Q

Give the hormone binding protein functions

A
  • Serve as hormone reservoir
  • Hormone buffers
  • Reduce hormone loss
83
Q

Explain how hormone binding proteins act as hormone reservoirs

A
  • Free hormone diffuses into cells
  • Reduces free concentration
  • Released from bound in order to replace
  • Leads to equilibrium
84
Q

Explain how hormone binding proteins act as hormone buffers

A
  • Respond to increased/decreased hormone secretion
  • Only use around 50% of binding capacity in normal situations so always have empty slots
  • Means that a small increase in hormone will not necessarily stimulate tissues
85
Q

Explain how hormone binding proteins act to reduce hormone loss

A
  • Prevent excretion via the kidney
  • Proteins cannot pass through the glomerulus into the ultrafiltrate and so are retained
  • Free hormones lost
86
Q

What are the elimination mechanisms for hormones?

A
  • Enzymatic degradation
  • Within target cells after binding
  • Via liver and kidney
87
Q

How does elimination affect function of a hormone?

A
  • Speed of removal affects hormone’s ability to have fast or slow action
  • Fast action if removed quickly
  • Slow action if removed slowly
88
Q

Explain why epinephrine has a fast action

A
  • Rapid release from adrenal medulla
  • Immediate action on tissues and fast return to normal (short half life)
  • Water soluble hormone, binds receptors and the enzymatically degraded by cell
89
Q

Explain why thyroxine (T4) has a slow action

A
  • Circulates as bound mostly
  • Bound ressitant to degradation
  • Once delivered to cell converted to T3 which enters cell and alters gene expression (which takes time)
  • Or converted to water soluble compounds by liver and excreted in urine
  • More steps to go through to elieict action and more steps for elimination so takes longer
90
Q

What are the main factors affecting hormone responses?

A
  • Variation by tissue
  • Variation by time
  • Variation by dose
  • Status of target tissue
91
Q

Explain how variation by tissue affects hormone responses

A
  • Tissues respond differently to same hormone
  • E.g. T4
  • increases cellular metabolism. Most effect in heart and gastric mucosa, some effect in skeletal muscle and no effectin spleen and brain
  • Due to lack/differing density in receptos
  • Different levels of machinery in different cells alters ability and degree to which a tissue can respond
92
Q

Explain how variation by time affects hormone responses

A
  • Intital response to hormone may differ from delayed response
  • Timing of response varies by species, age, specific hormone
  • Older patietns respond less will to retinoids
  • Hormone formualtion also affects its half life (and thus time time it is able to cause response)
93
Q

Explain how variation by dose affects hormone responses

A
  • Responses associated with hormone is for physiological range
  • Hormone levels outside physiological range may elicit different responses e.g. steroid therapy
  • Short term vs long term treatment
  • Long term may lead to suppression of own production
94
Q

Explain how status of target tissue affects hormone responses

A
  • With overstimulation, target tissues hypertrophy
  • With understimulation will atrophy
  • i.e. ability and degree to which tissue can and will respond
95
Q

What tests can be used to measure hormones?

A
  • ELISA
  • RIA
  • Clearance rate
  • Secretion rate
96
Q

Explain how clearance rate can be measured

A
  • Radioactively labelled hormone

- Or halt secretion

97
Q

Explain how secretetion rate can be measured

A

If concentration remains stable, then assume that concentration = clearance

98
Q

What is bound hormone representative of?

A

The amount being produced

99
Q

What is free hormone representative of?

A

The active amount, usually very low for lipid soluble

100
Q

What hormones are produced by the heart, intestine, kidney and placenta?

A
  • Heart: atrial natriuretic peptide (ANP)
  • Intestine: cholecystokinin, gastrin
  • Kidney: calcitriol, EPO, renin
  • Placenta: chorionic gonadotrophins

Endo (30 decks)

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