REB 2. Cellular Mechanisms of Hormone Action Flashcards
(26 cards)
What are the 2 systems that coordinate communication throughout the body?
[1] Endocrine System
[2] Nervous System
What are characteristics of the endocrine system?
- slower, but long-acting responses
- include reproduction, development, energy metabolism, growth and behaviour
- uses hormones
What are characteristics of the nervous system?
- conveys high-speed electricla signals along neurons
- these signals regulate other cells
- uses electrical signals
What is the difference between endocrine and exocrine glands?
Endocrine - release chemical substances directly into the bloodstream
Exocrine - the chemical substances are secreted into ducts (e.g. for enzymes)
What are hormones?
- biochemical messengers
- released into endocrine glands
- has an impact on gene expression/protein state
- they complement neurotransmitters
What is the difference between neurotransmitters and hormones?
Neurotransmitters - work through adjacent cell contact
Hormones - work by broadcasting a message
What is the main regulation mechanism for regulation within the endocrine system?
Regulated by Feedback
- in particular, Negative Feedback
- Positive Feedback has an opposite effect
What are the 3 main types of hormonal signalling that acts upon cells?
[1] Endocrine Signalling - enters the blood stream to act on cells (usually acts on distant sites, but may also act locally)
[2] Paracrine Signalling - the target cells lie near the secreting cells
[3] Autocrine Signalling - the target cell is also the secreting cell
How are hormones specific and potent?
- although concentration of hormones are low, they only bind onto specific receptors
- the specificity and potency is delivered through receptors
Describe the basic principle/mechanism of how a hormone works after a stimulus is received.
- stimulus is received + processed by endocrine gland
- hormones released into blood
- hormones carried to target tissues where they bind (with high specificity) to receptors
What actions/changes may hormones produce in tissues/cells?
[1] altering plasma membrane permeability [by closing/opening protein channels]
[2] regulating expression of functional proteins [via gene activation or suppression]
[3] moderating enzyme activity [via activation or deactivation]
[4] inducing or suppressing release of secretory products
[5] stimulating mitosis and cell division
What are the 2 main factors influencing the degree of cellular response? (and some examples)
[1] Delivery of Hormone
- rate of synthesis + secretion of hormone
- proximity of target cell to hormone source
- the rate at which hormones dissociate from carrier proteins
- rate of conversion from inactive to active forms
- rate of clearance by liver/kidney
[2] Receptor/Tissue Status
- Density and state of occupancy of receptors
- Affinity of receptors for hormone
- Desensitization of receptor
What are the 4 main categories that we use to classify hormones?
[1] Chemical Nature/Hormone Structure
- Steroids, Peptides, Glycoproteins
[2] Solubility
- Lipophilic vs. Hydrophilic
- In other words, hydrophobic vs. hydrophilic
- Lipophilic = Hydrophobic
- Lipophobic = Hydrophilic
[3] Cellular Binding Site/Receptor Location
- Intracellular vs. Cell Surface
[4] Receptor Basis
- G-Protein Receptors
- Secondary Messengers
- Kinase Receptors
What are the 4 main hormone structures and some characteristics of each?
[1] Steroid Hormones
- derived from cholesterol (e.g. testosterone and estrogen)
- hydrophobic + travel bound to transport protein in blood
[2] Peptide Hormones
- short chain amino acids (e.g. oxytocin or insulin)
[3] Protein Hormones
- long chain amino acids/complex proteins (e.g. TSH)
[4] Amine Hormones
- amino acid derivatives (e.g. epinephrine, thryoxine)
- derived from modification of amino acids
- mainly synthesized from tryptophan and tyrosine
- can be both hydrophobic or hydrophilic
What are the 2 main classes of hormones based on solubility?
[1] Hydrophilic
- soluble and readily diffuses into the blood
[2] Hydrophobic
- poorly water soluble
- binds to tranporter proteins/plasma proteins within the blood circulation
What are the 2 main classes of hormones based on its cellular binding site? Give a general overview of how these processes work.
[1] Water-Soluble Hormones
- unable to diffuse through cell membrane
- their receptors are located at the extracellular surface
- this initiates a signalling cascade that is carried out by second messengers
- “rapid” metabolic effects
[2] Lipid-Soluble Hormones
- readily diffuse through cell membrane
- they can reach the intracellular receptor within the cytosol or nucleus
- the hormone-receptor complex binds to a segment of DNA triggering transcription of target gene to mRNA
- “slow” developmental effects
What are the steps in hydrophobic intracellular signalling?
- Diffusion
- hydrophobic hormones can readily diffuse through the lipid bilayer of the cell membrane to reach the intracellular receptor - Binding
- encounters specific receptors within cell - Translocation
- activated receptor translocates to the nucleus - Hormone Response Elements
- Once in nucleus, activated receptor binds to the hormone response elements (HREs) of DNA - [DELTA] Expression/Change in Expression
- this binding drives changes in mRNA and resulting protein expression
What are Hormone Response Elements (HRE)?
- they are regions of DNA that the (hydrophobic) hormone-receptor complex binds to
- they are normally upstream of the 5’ transcription initiation site
- nuclear receptor proteins/transcription factors can also bind to them (providing further layer of complexity/control)
What are the steps in hydrophilic signalling?
- Binding
- encounters specific receptors on cell membrane
- typically G-protein coupled receptors (GPCRs)
- receptors carry signal across membrane - Intracellular Signalling
- activated G protein activates adenylate cyclase - this converts ATP to cAMP which propagates the signal through the cell - Activation of Protein Kinase A (PKA)
- cAMP targets and activates PKA in the cytosol - Phosphorylation
- PKA triggers selective phosphorylation of cellular proteins (phosphorylation cascade)
- e.g. metabolic enzymes, nuclear transcription factors
What are some functions of Protein Kinase A (PKA)?
[1] Inhibition of Glycogen Synthesis
[2] Promotion of Glycogen Breakdown
In extracellular/hydrophilic hormone signalling, how is the phosphorylation cascade shut off?
PKA activated Phosphodiesterase (PDE) within the cytosol which deactivates cAMP - turns off the signal until next stimulus
Explain a bit about the process of another secondary messenger, Calcium, starting from how the whole process is activated and what intermediates are created.
- G-proteins activate the Phospholipase C enzyme
- Phospholipase C cleaves membrane-bound phospholipid (PIP2) into:
- Diacylglycerol (DAG)
- Inositol Triphosphate (IP3)
Functions of DAG:
- activates protein kinases that initiate phosphorylation cascade
Functions of IP3:
- causes calcium ions to be released from storage sites in cytosol
- (1) calcium influences enzymatic and other cellular activities
- (2) binds to calcium-binding protein, calmodulin, which is able to modulate protein kinase within the cell
What are the 2 main functions of calcium as a second messenger?
[1] calcium influences enzymatic and other cellular activities
[2] calcium binds to calcium-binding proteins, calmodulin, which is able to modulate protein kinase within the cell
What is cGMP and how is it created? What is an example of the use of cGMP?
- it is a secondary messenger
- GTP is converted to cGMP through the membrane-bound receptor Guanylate Cyclase
- Example: Atrial Natriuretic Peptide
-Increased B.P induces ANP release from the cardiac
atria- The binding of ANP to its receptor causes the
conversion of GTP to cGMP - cGMP activates a Protein Kinase G (PKG) and also
directly regulates ion channels - ANP induces reduction in ECF volume by increasing
renal sodium excretion
- The binding of ANP to its receptor causes the
