Eicosanoids Overview and Their Effects

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Questions and Answers

Which class of eicosanoids is primarily involved in the mediation of pain signals?

HETES

Leukotrienes

Prostaglandins (correct)

Thromboxanes

What effect do eicosanoids have on blood pressure regulation?

Promote sodium and water retention (correct)

Induce vasodilation

Inhibit inflammation

Increase heart rate

In the clinical context provided, what condition is likely indicated by elevated plasma levels of prostaglandin E2 and leukotriene B4?

Rheumatoid arthritis

Gout

Osteoarthritis

Inflammatory arthritis (correct)

Which of the following treatments is suggested for rapid reduction of inflammation?

Corticosteroids Signup and view all the answers

What lifestyle modification is recommended to help modulate inflammation?

Increase omega-3 fatty acids Signup and view all the answers

Which consequence is NOT an effect directly associated with eicosanoids?

Bone mineralization Signup and view all the answers

What condition presented in the patient profile is linked with elevated eicosanoids contributing to inflammation?

Inflammatory arthritis Signup and view all the answers

Which eicosanoid class is primarily involved in the protection of the stomach lining?

Prostaglandins Signup and view all the answers

What happens to Ga when it hydrolyzes GTP?

It becomes inactive and binds to the inhibitory bg complex. Signup and view all the answers

Which enzyme is responsible for converting cAMP to AMP?

Phosphodiesterase Signup and view all the answers

Which type of receptor is associated with insulin and many growth factors?

Receptor tyrosine kinases Signup and view all the answers

What is the primary role of adenylate cyclase in the signaling process?

Catalyzing the formation of cAMP from ATP. Signup and view all the answers

Which of the following best describes the action of steroid hormones?

They bind to nuclear receptors and regulate gene expression. Signup and view all the answers

What is the primary reason that only free hormones are biologically active?

Bound hormones do not attach to the receptor. Signup and view all the answers

What role do binding proteins play in hormone transport in the bloodstream?

They prevent overaction of hormones by regulating their binding. Signup and view all the answers

What percentage of total steroids in circulation is typically bound to proteins?

90-99% Signup and view all the answers

Which specialized binding protein is known for binding cortisol?

Corticosteroid Binding Globulin (CBG) Signup and view all the answers

How does the presence of binding proteins affect hormone fluctuations in the blood?

They stabilize hormone levels by creating a reservoir. Signup and view all the answers

Which hormone typically has the lowest concentration in the blood?

Aldosterone Signup and view all the answers

Which type of hormones usually remain mostly bound to carrier proteins in the blood?

Steroid hormones Signup and view all the answers

What is the function of non-specialized binding proteins in hormone transport?

Low affinity but high capacity for binding. Signup and view all the answers

What does chronic hormone secretion refer to?

Relatively constant concentration of hormone Signup and view all the answers

What happens to receptor numbers during down-regulation?

Rate of synthesis decreases after prolonged hormonal exposure Signup and view all the answers

Which mechanism increases sensitivity to a hormone by increasing receptor numbers?

Up regulation Signup and view all the answers

What is a characteristic of protein/peptide hormones regarding receptor location?

Receptors must be on the plasma membrane Signup and view all the answers

What function do cytoplasmic or intracellular domains of receptors serve?

Interact with intracellular molecules Signup and view all the answers

What occurs when hormone exposure is prolonged in relation to receptor molecules?

Rate of receptor synthesis may decrease Signup and view all the answers

What do extracellular domains of hormone receptors interact with?

Hormones in the bloodstream Signup and view all the answers

What effect does FSH stimulation have on the ovaries?

Increases LH receptor numbers Signup and view all the answers

Study Notes

Major Classes of Eicosanoids

Prostaglandins
Thromboxanes
Prostacyclins
Leukotrienes
HETEs

Synthesis of Eicosanoids

Diacylglycerol or phospholipid is converted to arachidonic acid
Arachidonic acid is then processed by enzymes
Prostaglandin H2(PGH2) is a precursor to various prostaglandins (PGD2, PGE2, PGF2)
Prostacyclin and thromboxane are also derived from other intermediates
Lipoxygenase is involved in the production of leukotrienes

Effects of Eicosanoids

Induce inflammation
Mediate pain signals
Induce fever
Cause smooth muscle contraction (including uterine contractions)
Cause smooth muscle relaxation
Protect stomach lining
Stimulate platelet aggregation
Inhibit platelet aggregation
Cause sodium and water retention

Clinical Relevance

Elevated eicosanoids contribute to inflammation and pain.
NSAIDs can be used for rapid inflammation reduction.
Corticosteroids may be considered as additional treatment if needed.
Disease-modifying antirheumatic drugs (DMARDs) might be necessary if the condition progresses to RA.
Lifestyle changes like increasing omega-3 fatty acids intake are beneficial to help modulate inflammation.

Synthesis of Hormone Derivatives of Tryptophan

L-Tryptophan -> 5-Hydroxytryptophan -> Serotonin -> N-acetylserotonin -> Melatonin

Synthesis of Hormone Derivatives of Tyrosine

Tyrosine -> DOPA -> Dopamine -> Noradrenaline -> Adrenaline

Thyroid Hormone Derivatives

The synthesis of thyroid hormones involves tyrosine and iodine.
- Thyroxine (T4) and Triiodothyronine (T3) are synthesized from tyrosine.

Transport of Hormones

Peptide hormones dissolve readily in plasma, but are still carried bound to carrier proteins.
Steroid hormones are mostly insoluble in plasma, and typically carried bound to proteins
The resulting affinity of the binding can be strong
Only free hormone is biologically active, and is in equilibrium with bound hormone.

Binding Hormones

Specialized binding proteins have high affinity but low capacity.
Examples include Cortisol binding globulin (CBG) and Thyroxine-binding globulin (TBG).
Non-specialized binding proteins have low affinity but high capacity.
Examples include plasma albumins and also TBPA.

Consequences of Binding

Binding prevents hormones from acting too rapidly and prevents large fluctuations in active hormone levels
Increases the total amount of hormone in the blood.
Inactivation and excretion in urine and liver are delayed.

Hormone Concentration in Blood

Peptide hormone levels are typically low (10^-12 to 10^-9 M).
Levels of steroid hormones are usually higher (10^-7 to 10^-10 M).
Aldosterone is an exception with levels typically similar to peptides (10^-10 M).

Patterns of Hormone Secretion

Chronic hormone secretion maintains relatively constant levels over time.
Acute hormone secretion is an immediate response to a stimulus and is often characterized by a rapid increase and decrease.
Episodic or cyclic hormone secretion follows a pattern, often repeating over time

Hormone Specificity

Hormones typically only affect specific target tissues.
Receptors are present on target cells, and receptor number is not constant.
Hormones are degraded and replaced regularly.
Down-regulation of hormones occurs due to prolonged hormonal exposure, reducing the number of receptors.
Up-regulation of hormones occurs by increasing receptor synthesis to cause increased sensitivity to the hormone.

Receptor Location - Protein/Peptide Hormones

These hormones cannot pass through plasma membranes.
Receptors are located on the plasma membrane, and have:
- Extracellular domains.
- Trans-membrane domains that anchor the receptor.
- Intracellular domains that interact with other intracellular molecules.

cAMP Second Messenger System

Hormone binds its receptor which activates a G protein (Gs).
The G protein activates adenylate cyclase.
Adenylate cyclase converts ATP to cAMP, which acts as a second messenger.
cAMP activates protein kinases, which trigger various cellular responses.

Turning off the signal

The G-protein is inactivated (hydrolyzing GTP to GDP and Pi).
cAMP is broken down to AMP by phosphodiesterases.

Various Cellular Responses

cAMP can result in various cellular responses, including enzyme secretion, lipid breakdown, glycogen synthesis and glycogen breakdown, and others.

Other Protein Hormone Receptors

Receptor tyrosine kinases (RTKs) on the plasma membrane have intrinsic tyrosine kinase activity.
Kinase activity is stimulated when hormone receptor pairs bind, resulting in signal transmission within the cell.
Binding causes autophosphorylation of the receptor.
Signals are transmitted by activated proteins to the cells interior (cytoplasm or nucleus).

Steroid Hormone Action

Steroid hormones can pass through the plasma membrane.
Steroid hormones bind to cytoplasmic or nuclear receptors.
The hormone-receptor complex interacts with DNA, and this alters gene expression.
Transcription of mRNA.

Thyroid Hormone Nuclear Receptor

Thyroid hormones bind to nuclear receptors, resulting in altered gene expression.
This regulates the amount of various proteins.

Hormones Known to Act Via cAMP

Adrenocorticotropic hormone (ACTH)
Follicle Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
Thyroid-stimulating hormone (TSH)
Chorionic gonadotropins (hCG)
β-Endorphins & Enkephalins
Anti-diuretic hormone (ADH)
Glucagon
Parathyroid hormone (PTH)
Calcitonin
Epinephrine
Norepinephrine

Hormones Known to Act Via cGMP

Atrial natriuretic factor (ANF)
Nitric oxide (NO)

Hormones Known to Act Via Phosphotidyl Inositol/Calcium

Thyrotropin-releasing hormone (TRH)
Gonadotropin-releasing hormone (GnRH)
Gastrin
Cholecystokinin (CCK)

Hormones Known to Act Via Tyrosine Kinase Cascade.

Insulin
Growth hormone (GH)
Prolactin (PRL)
Oxytocin
Insulin-like growth factors (IGF-I, IGF-II)

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Description

This quiz focuses on the major classes, synthesis, and clinical relevance of eicosanoids. Explore various types such as prostaglandins and leukotrienes, and their roles in inflammation and pain relief. Understand how these compounds interact within the body and their significance in medical treatments.