Eicosanoids

What are Eicosanoids

Eicosanoids are a group of bioactive lipid molecules derived from arachidonic acid

5 Major Classes of Eicosanoids

Prostaglandins
Thromboxanes
Prostacyclins
Leukotrienes
HETES

Diagram for process of Synthesis of Eicosanoids

Stopping Cox inhibitors means …..

Preventing pain

Effects of Eicosanoids

• Induction of inflammation
• Mediation of pain signals
• Induction of fever
• Smooth muscle contraction (including uterus)
• Smooth muscle relaxation
• Protection of stomach lining
• Simulation of platelet aggregation
• Inhibition of platelet aggregation
• Sodium and water retention

Use of prostaglandins in medicine

Used to induce labour

What would the diagnosis be for John

Likely inflammatory arthritis, with elevated eicosanoids contributing to inflammation and pain

What treatment could be given for the elevated eicosanoids

Eicosanoid Modulation: Targeting the eicosanoid pathway

In John’s blood pressure of 150/90, which number is more significant

The 90 is more significant than the 150 because the 150 is highly variable

Why are all hormones measured if fertility is an issue

The autonomic nervous system has a big influence over reproduction

Which is more powerful/potent

T3 is about 10 times more potent (more powerful) than T4

Are T3 or T4 given more to patients

T4 is given more to patients as the side effects of T3 are far greater

99% of iodine that enters the body goes where

straight to the thyroid gland

How are peptide/protein hormones transported

Dissolve easily in plasma

Carried bound to carrier proteins

How are steroid/amine hormones transported

Relatively Insoluble in plasma
Majority (>90%) of Steroids Transported Bound to Protein

What bonds hold steroid/amine hormones and proteins together

Weak Chemical Bonds - Hydrogen/ ionic bonds/van der Waals
(Resulting Affinity can be Strong)

What percentage of hormones are free

Typically Only 1-10%

When measuring steroids do you measure bound/free/both

Both

Why measure most bound and free steroids

Someone with liver failure or issues with the liver may have issues with binding proteins so they might have less % of hormones bound

Are bound and free hormone ever unbalanced

No - always in equilibrium

Specialised Binding proteins have a high/low affinity for hormones

High

Specialised Binding proteins have a high/low capacity for hormones

Low

Non-Specialised Binding proteins have a high/low affinity for hormones

Low

Non-Specialised Binding proteins have a high/low capacity for hormones

High

Are Plasma Albumins & TBPA specialised or non specialised binding proteins

Non specialised

Are CBG-Cortisol Binding Globulin & TBG- Thyroxin Binding Globulin specialised or non specialised binding proteins

Specialised

Do specialised / non specialised binding proteins bind steroids & thyroid hormones

Non specialised

What type of binding protein is more abundant

Non specialised

Effect of binding proteins

Prevents Over Action of Hormone since only “Free” is Biologically Active

Prolongs Effect of Hormone

Prevents Large Fluctuations in Active Hormone Levels

How does binding prolong the effect of hormones

Inactivation in Liver and Excretion in Urine is Delayed
Increases Total Hormone Carrying Capacity of Blood

How does binding Prevent Large Fluctuations in Active Hormone Levels

Increased Reservoir of Hormone
Equilibrium Between Free and Bound Forms

Peptide hormone concentration in blood

How are peptide hormone levels in blood measured

Peptides are in such low levels that they can be very hard to measure. They are stimulated and then the patient's response to the stimulus is measured

Steroid concentration in blood

Which of these graphs represent chronic, episodic & acute hormone secretion

Top = Chronic (relatively constant concentration of hormone)

Middle = Acute (hormone secretion in response to a stimulus)

Bottom = Episodic (cyclic)

Which pattern of hormone secretion is most common & most rare

Most common = Episodic

Most rare = Chronic

Example of hormone with episodic pattern of secretion (& it’s pattern)

Growth hormone

Should be high at 2am and low at 2pm

Are hormones specific for the tissues they affect

Yes - Hormones Affect Only Target Tissues with Specific Receptors

What parts of the cell can receptors be present on

Cell Membrane or Cytoplasm

Does the number of receptors on a cell ever change

yes - they get degraded and replaced regularly

What can increase the rate at which receptor molecules are degraded

Prolonged hormone exposure

(Explains the desensitization that can occur to some drugs)

Example of what can increase the rate at which receptor molecules are synthesised

FSH stimulation of the ovary causes an increase of LH receptors

What prevents Protein/Peptide Hormones from passing through plasma membranes

Size and Charge

Where are Protein/Peptide Hormone receptors located

On the plasma membrane (the hormones can’t pass through the membrane so the receptors must be on the membrane itself)

What are the 3 parts of Protein/Peptide Hormone receptors & what are their roles

Extracellular Domain: Interact with & Binds Hormone (Ligand-Binding Domain)

Trans-Membrane Domains (Span Cell membrane): Hydrophobic Stretches of Amino Acids that Anchor the Receptor in Cell Membrane

Cytoplasmic / Intracellular Domains: Effector region - Interact with Other Intracellular Molecules, Generates Second Messengers

Process of cAMP second messenger system

When the hormone binds to the receptor, GDP is converted to what?

GTP

How is the cAMP Second Messenger System signal turned off

Cellular responses from cAMP

After a peptide hormone binds with a receptor, is the signal amplified or degraded as it relays through molecules

Amplified

Location of receptors for insulin & many growth factors

Trans-membrane receptors

What specifically is a receptor for insulin & many growth factors

tyrosine kinase

What process activates RTK (tyrosine kinase)

Autophosphorylation

Why does steroid action tend to be slower

Steroids can't dissolve in plasma but receptors for steroids are found in the cytoplasm or the nucleus

What do these have in common

They activate the cAMP second messenger system

What do these activate:

cGMP

What do these activate:

Phosphatidyl inositol/calcium (or both)

What do these activate:

Tyrosine Kinase / Phosphatase cascade