Hormone Signaling Pathways Quiz

Major Classes of Eicosanoids

• Prostaglandins
• Thromboxanes
• Prostacyclins
• Leukotrienes
• HETEs

Synthesis of Eicosanoids

• Arachidonic acid is a precursor for eicosanoids
• Lipoxygenase is one of the enzymes that convert arachidonic acid into other substances leading to the synthesis of leukotrienes.
• Cyclooxygenase (COX-1 and COX-2) enzymes convert arachidonic acid into prostaglandins, thromboxanes, and prostacyclins.

Effects of Eicosanoids

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

Clinical Relevance

• Elevated eicosanoids can contribute to inflammation and pain, possibly indicating inflammatory arthritis.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids might be used to reduce inflammation.
• Disease-modifying antirheumatic drugs (DMARDs) such as methotrexate might be considered.
• Lifestyle modifications, such as increasing omega-3 fatty acids intake, can help to modulate eicosanoid pathways.

Synthesis of Hormone Derivatives of Tryptophan

• L-Tryptophan is a precursor to serotonin and melatonin.
• The enzymes tryptophan-5-hydroxylase, 5-Hydroxytryptophan decarboxylase, serotonin N-acetyltransferase, and hydroxindole-0-methyltransferase catalyze these transformations.

Synthesis of Hormone Derivatives of Tyrosine

• Tyrosine is a precursor for dopamine, norepinephrine, epinephrine
• The key enzymes include tyrosine hydroxylase (TH), dopa decarboxylase (DDC), dopamine beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT).
• The synthesis of thyroid hormones (thyroxine (T4), triiodothyronine (T3)) involves the iodination of tyrosine molecules.

Transport of Hormones

• Peptide/protein hormones dissolve readily in plasma but may still be bound to carrier proteins.

• Steroid/amine hormones are largely insoluble in plasma; therefore, they usually bind to carrier proteins (mainly albumin) for transport–resulting in a high bond affinity.

• Only the unbound (free) form of hormone is physiologically active.

Binding Proteins

• Specialized binding proteins have high affinity but low capacity, and non-specialized binding proteins have low affinity but high capacity.

Consequences of Hormone Binding

• Preventing hormone action from overwhelming the system.
• Prolonging hormone effect
• Inactivation in liver or excretion in urine are delayed
• Increase total amount of hormone carrying capacity in blood
• Prevent fluctuations in active hormone levels.
• Increases reservoir of hormone available.
• Maintains equilibrium between bound and free hormone forms.

Hormone Concentration in Blood

• Peptide hormone concentrations are typically low, while steroid hormone concentrations are markedly higher, including cortisol, steroid sex hormones, with aldosterone being an exception.

Patterns of Hormone Secretion

• Chronic secretion shows relatively constant hormone levels over time.

• Acute secretion is a rapid response to a stimulus, with hormone levels rising and quickly returning to baseline.

• Episodic (cyclic) secretion shows varying hormone levels at different times (for example, daily or seasonal fluctuations in some hormones).

Hormone Specificity

• Receptors for hormones are found on or in cells, and their presence is not constant; they are degraded and replaced.

• Down-regulation is a decrease in the synthesis of receptors, occurring with chronic hormone exposure.

• Up-regulation is an increase in receptor synthesis, increasing cellular sensitivity to the hormone.

Receptor Location

• Protein/peptide hormones are too large or charged to pass the plasma membrane directly.
• Receptors are located on the plasma membrane in this situation.
• Extracellular domains enable interaction and binding of hormone ligands, while membrane-spanning domains anchor the receptor to the membrane.
• Cytoplasmic or intracellular domains interact with other intracellular molecules and trigger secondary messenger signalling cascades.

cAMP Second Messenger System

• Hormones bind to receptors, initiating a cascade of events culminating in an intracellular second messenger, cAMP.
• This activates protein kinases, triggering responses in the target cell.

Turning Off the Signal

• GTP hydrolysis on Gα protein turns the signaling pathway off.

• Phosphodiesterases catalyze the hydrolysis of cAMP to AMP.

Various Cellular Responses from cAMP

• Cellular responses from cAMP are varied and depend on the specific target cell and pathway.
• cAMP-dependent protein kinases can activate or inhibit many enzymes or processes

Amplification

• The initial binding of a hormone molecule triggers a specific cascade in a target cell.
• The cascade triggers many molecules to amplify the signaling process as it propagates through the cell and beyond.

PI Second Messenger System

• Hormones binding to surface receptors trigger a cascade of events leading to the release of second messengers.
• These trigger responses within the cell like controlling the release of various products via exocytosis.

Other Protein Hormone Receptors

• Transmembrane receptors with intrinsic tyrosine kinase activity, including receptors for insulin and growth factors, have intracellular domains.
• Receptors are activated via signal molecule dimerization and subsequent autophosphorylation of their intracellular domains.
• Activated signaling proteins transmit signals inside the cytoplasm and initiate downstream effects.

Steroid Hormone Action

• Steroid hormones diffuse directly through cell membranes, interacting with cytoplasmic or nuclear receptors.
• These actions lead to changes in gene expression and ultimately protein synthesis.

Thyroid Hormone Nuclear Receptor

• Thyroid hormones interact with nuclear receptors, directly activating specific genes and impacting RNA synthesis resulting in a thyroid hormone-specific response.

Known to Act Via cAMP

• List of hormones that use the cAMP second messenger system.

Known to Act Via cGMP

• List of hormones that use the cGMP second messenger system.

Known to Act Via Tyrosine Kinase/Phosphatase

• List of hormones that use the Tyrosine Kinase/Phosphatase cascade pathway.

Test your knowledge of hormone signaling mechanisms, including cAMP pathways, receptor functions, and the effects of hormone exposure on receptor regulation. This quiz covers key concepts related to hormone receptors and their roles in cell signaling.