REB 2. Cellular Mechanisms of Hormone Action Flashcards

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1
Q

What are the 2 systems that coordinate communication throughout the body?

A

[1] Endocrine System

[2] Nervous System

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2
Q

What are characteristics of the endocrine system?

A
  • slower, but long-acting responses
  • include reproduction, development, energy metabolism, growth and behaviour
  • uses hormones
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3
Q

What are characteristics of the nervous system?

A
  • conveys high-speed electricla signals along neurons
  • these signals regulate other cells
  • uses electrical signals
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4
Q

What is the difference between endocrine and exocrine glands?

A

Endocrine - release chemical substances directly into the bloodstream
Exocrine - the chemical substances are secreted into ducts (e.g. for enzymes)

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5
Q

What are hormones?

A
  • biochemical messengers
  • released into endocrine glands
  • has an impact on gene expression/protein state
  • they complement neurotransmitters
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6
Q

What is the difference between neurotransmitters and hormones?

A

Neurotransmitters - work through adjacent cell contact

Hormones - work by broadcasting a message

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7
Q

What is the main regulation mechanism for regulation within the endocrine system?

A

Regulated by Feedback

  • in particular, Negative Feedback
  • Positive Feedback has an opposite effect
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8
Q

What are the 3 main types of hormonal signalling that acts upon cells?

A

[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

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9
Q

How are hormones specific and potent?

A
  • although concentration of hormones are low, they only bind onto specific receptors
  • the specificity and potency is delivered through receptors
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10
Q

Describe the basic principle/mechanism of how a hormone works after a stimulus is received.

A
  1. stimulus is received + processed by endocrine gland
  2. hormones released into blood
  3. hormones carried to target tissues where they bind (with high specificity) to receptors
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11
Q

What actions/changes may hormones produce in tissues/cells?

A

[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

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12
Q

What are the 2 main factors influencing the degree of cellular response? (and some examples)

A

[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
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13
Q

What are the 4 main categories that we use to classify hormones?

A

[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
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14
Q

What are the 4 main hormone structures and some characteristics of each?

A

[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
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15
Q

What are the 2 main classes of hormones based on solubility?

A

[1] Hydrophilic
- soluble and readily diffuses into the blood

[2] Hydrophobic

  • poorly water soluble
  • binds to tranporter proteins/plasma proteins within the blood circulation
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16
Q

What are the 2 main classes of hormones based on its cellular binding site? Give a general overview of how these processes work.

A

[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
17
Q

What are the steps in hydrophobic intracellular signalling?

A
  1. Diffusion
    - hydrophobic hormones can readily diffuse through the lipid bilayer of the cell membrane to reach the intracellular receptor
  2. Binding
    - encounters specific receptors within cell
  3. Translocation
    - activated receptor translocates to the nucleus
  4. Hormone Response Elements
    - Once in nucleus, activated receptor binds to the hormone response elements (HREs) of DNA
  5. [DELTA] Expression/Change in Expression
    - this binding drives changes in mRNA and resulting protein expression
18
Q

What are Hormone Response Elements (HRE)?

A
  • 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)
19
Q

What are the steps in hydrophilic signalling?

A
  1. Binding
    - encounters specific receptors on cell membrane
    - typically G-protein coupled receptors (GPCRs)
    - receptors carry signal across membrane
  2. Intracellular Signalling
    - activated G protein activates adenylate cyclase - this converts ATP to cAMP which propagates the signal through the cell
  3. Activation of Protein Kinase A (PKA)
    - cAMP targets and activates PKA in the cytosol
  4. Phosphorylation
    - PKA triggers selective phosphorylation of cellular proteins (phosphorylation cascade)
    - e.g. metabolic enzymes, nuclear transcription factors
20
Q

What are some functions of Protein Kinase A (PKA)?

A

[1] Inhibition of Glycogen Synthesis

[2] Promotion of Glycogen Breakdown

21
Q

In extracellular/hydrophilic hormone signalling, how is the phosphorylation cascade shut off?

A

PKA activated Phosphodiesterase (PDE) within the cytosol which deactivates cAMP - turns off the signal until next stimulus

22
Q

Explain a bit about the process of another secondary messenger, Calcium, starting from how the whole process is activated and what intermediates are created.

A
  1. G-proteins activate the Phospholipase C enzyme
  2. 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
23
Q

What are the 2 main functions of calcium as a second messenger?

A

[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

24
Q

What is cGMP and how is it created? What is an example of the use of cGMP?

A
  • 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
25
Q

Explain the process by which insulin receptors work and how the signal is transmitted to lead to glucose uptake and glycogen synthesis (insulin release during high glucose levels).

A
  • insulin receptor is a Tyrosine-Specific Protein Kinase (NO second messengers!)
  • after ligand binding, the receptors dimerize
  • they both undergo autophosphorylation
  • the Insulin Receptor Substrate (IRS-1) binds to phosphate groups and get phosphorylated
  • this further propagates signal transduction
  • leads to (a) glucose uptake
    (b) glycogen synthesis
26
Q

What are the 2 main diseases that may arise due to a defect in a hromone receptor.

A

[1] Type II Diabetes (insulin resistance)

  • reduction/insensitive to insulin receptor results in downstream signalling deficits and increased blood glucose levels
  • not reactive to receptor so signal isn’t transmitted

[2] Graves’ Disease (TSH receptor)

  • autoantibodies against Thyroid Stimulating Hormone (TSH)
  • the autoantibodies bind to TSH receptor resulting in increased thyroid hormone production
  • leads to hyperthyroidism