Hormone Receptor Pathways

Jul 10, 2024

Hormone Receptor Pathways - Lecture Notes

Introduction

  • Focus on important hormone receptor pathways.
  • Hormones can be classified as peptide hormones or steroid hormones.
    • Peptide hormones: Water-soluble, cannot penetrate cell membranes, require membrane receptors and second messenger systems.
    • Steroid hormones: Lipid-soluble, derived from cholesterol, can pass through cell membranes and have intracellular receptors.

Peptide Hormones and Second Messenger Systems

  • Work through second messenger systems (e.g., GQ pathway, G stimulatory pathway).

G Stimulatory Pathway

  1. Hormone Binding: Epinephrine binds to G-protein coupled receptor (GPCR).
  2. Activation: The receptor activates the G stimulatory protein (G_s) by swapping GDP for GTP.
  3. Effector Enzyme Activation: G_s activates adenylate cyclase on the cell membrane.
  4. cAMP Production: Adenylate cyclase converts ATP to cyclic AMP (cAMP).
  5. Activation of Protein Kinase A: cAMP activates protein kinase A (PKA).
  6. Phosphorylation of Target Proteins: PKA phosphorylates various proteins affecting:
    • Membrane permeability.
    • Metabolic pathways (e.g., glycolysis, gluconeogenesis).
    • Transcription factors leading to protein synthesis and cell growth.

GQ Pathway

  1. Hormone Binding: Oxytocin binds to G-protein coupled receptor.
  2. Activation: The receptor activates GQ protein (G_q) by swapping GDP for GTP.
  3. Effector Enzyme Activation: G_q activates phospholipase C (PLC).
  4. IP3 and DAG Generation: PLC converts PIP2 into IP3 and DAG.
  5. Activation of Protein Kinase C: DAG activates protein kinase C (PKC).
  6. Phosphorylation of Target Proteins: PKC phosphorylates various proteins.
  7. Calcium Release: IP3 binds to IP3 receptors on the smooth ER/sarcoplasmic reticulum causing Ca2+ release.
  8. Calcium Effects: Ca2+ binds calmodulin, activating kinases leading to:
    • Muscle contraction (via troponin or myosin phosphorylation).
    • Various cellular responses (e.g., metabolism, cell proliferation).

Steroid Hormones

  • Derived from cholesterol, lipid-soluble, can pass through cell membranes.

Generic Steroid Pathway

  1. Hormone Diffusion: Steroid hormone (e.g., testosterone) diffuses through the lipid bilayer.
  2. Binding to Intracellular Receptor: Hormone binds to receptor displacing heat shock proteins.
  3. Gene Activation: Hormone-receptor complex binds to hormone response element (HRE) on DNA.
  4. Protein Synthesis: Activation of gene transcription and translation leading to:
    • Protein synthesis (enzymes, structural proteins).
    • Regulation of metabolism, ion permeability, cell growth.

Inhibition of Pathways

  • Phosphodiesterase (PDE): Enzyme that degrades cAMP, regulating the pathway activity.

Summary

  • Covered G stimulatory and GQ pathways for peptide hormones.
  • Discussed the generic pathway for steroid hormones.
  • Explained the role of second messengers and phosphorylation in cellular response.

Key Takeaways: Peptide hormones act via membrane receptors and second messengers, while steroid hormones act via intracellular receptors and directly influence gene expression.