ENI - Hormones and Cell signalling Flashcards
Define autocrine signalling
Affects cell producing the hormone i.e. feeds back on self e.g. growth factors
Define paracrine signalling
Diffuses short distances to affect cells nearby e.g. neurotransmitters
Define endocrine signalling
Acts on target cells disant from site of synthesis e.g. hormones
Describe the functions of autocrine signalling
- 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
What are the consequences of signalling?
- Signal to survive
- Divide
- Differentiate
- Cell death
- Carry out specialised function
Compare lipid and water soluble hormones
- Lipid: require proteins for transport, bind to intracellular receptors
- Water: move freely through blood, bind to extracellular receptors
Compare cytokines and growth factors
- Growth factors: polypeptides that promote cell growth/proliferation
- Cytokines: factors associated with blood cells
- But no absolute distinction
What is the function of growth factors and cytokines?
- Control fundamental processes
- E.g. cell division (proliferation)
- Cell differentiation
- Apoptosis
Describe lipid soluble hormones
- 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
Give examples of lipid soluble hormones
- Steroid hormones
- Androgens
- Aldosterone
Outline the steps required in order for lipid soluble horones to initiate their action
- Bind to receptors
- Induce receptor shape change
- Bind to specific portion of DNA
- Regulate transcription of that part of DNA
- Increase or decrease
Desribe lipid soluble hormone receptors
- All structurally related, part of nuclear receptor superfamily
- Bind to DNA as homo or heterodimers
- Short DNA binding domain with zinc finger
What are the regions of lipid-soluble hormone receptors?
- Transcription-activating domain
- DNA binding domain
- Hormone binding domain
Describe the activation of the lipid-hormone receptor
- 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
Describe water-soluble hormones
- 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
List the intracellular signal transduction pathways triggered by water soluble hormones
- Adenyl cyclase (cyclic AMP)
- Guanyl cyclase (cyclic GMP)
- Phospholipase C, IP3 and DAG
- Tyrosine kinase
- Ion channels
What are the possible effects of water-soluble hormones binding to receptor protein?
- Cellular metabolism can change
- Proteins affecting gene expression altered
- Amount or location of cytoskeleton altered
What hormones does adenyl cyclase respond to?
- ACTH
- ADH
- FSH
- LH
- TSH
What hormones does guanylyl cyclase response to?
ANP (is rare)
What hormones does phospholipase C respond to?
Hypothalamic hormones TRH and GnRH
What hormones does tyrosine kinase respond to?
- Insulin
- Prolactin
- Growth hormone
- IGF
What hormones do ion channels respond to with respect to second messenger signalling of water-soluble hormones?
Hormones using multiple pathways
Give an overview of the intracellular signalling pathway for water soluble hormones
- 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
What are the 3 components of membrane receptors?
- External domain (binds ligand/hormone)
- Transmembrane domain
- Cytoplasmic/intracellular domain
What domain of the membrane receptor changes shape to convey the signal?
Intracellular (through action of transmembrane domain, passing signal from extra to intracellular)
What is the effect of the conformational change of the intracellular domain of the membrane receptor?
- Stimulates signalling pathway
- Usually activation of dormant enzymatic activity, often protein kinase
- Receptor phosphorylates intracellular proteins to further signal transduction
What is the advantage of the intracellular signalling pathways?
- 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
Describe the receptors for growth factors
- Have enzyme activity
- Tyrosine kinase
- Initiate signal that is propagated through cell by phosphorylation
Explain how the same signal can have different effects in different tissues/cells
- 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
Define half life
Teh time taken for the concentration of a signalling molecule to fal by half
What factors determine the hald life of a signalling molecule?
- Rate of destruction or removal of molecules
- Turnover rate (which depends on promptness of response when signal turned on)
Compare the half life of molecules that take a long time to synthesise vs molecules that take a short time to synthesise
- Long: long half life
- Short: short half life
What are the 4 main classes of cell surface receptors?
- Ion-channel-linked receptors
- G-protein linked
- Tyrosin kinase linked
- Receptors with intrinsic enzymatic activity
What are ion-channel-linked receptors usually used for?
Rapid synaptic signalling e.g.post-synaptic membranes, neuromuscular junction, nicotinic acetylcholine receptor, GABA receptors
Describe how ion-channel-linked receptors work
- 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
Describe the structure of G-protein coupled receptors
- 7 transmembrane receptor
- Single polypeptide chain with central hydrophobic region
- Spans plasma membrane 7 times, 7 loops
Explain how G-protein linked receptors work
- When ligand binds to 7 transmembrane receptor, changes shape of intracellular loop
- Allows recruitment and activation of G protein
- This activates enzyme
What is a G protein?
Guanine nucleotide binding protein (signal transduction protein). Composed of 3 different proteins
Explain how G proteins are activated
- 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
Outline the types of actions G proteins can have on adenylate cyclase and how
- Can activate or inhibit
- Speciaised proteins (Stimulatory or Inhibitory) and interaction depending on which receptor is activated