6 (R) - Hormones and RTK (Receptor tyrosine kinase) pathway

Types of Hormones

Classified by chemical structure: Amino-acid derived (amines, peptides, proteins) or lipid-derived (steroids)

Amine Hormones

Derived from single amino acids; examples include catecholamines (epinephrine) and melatonin

Peptide/Protein Hormones

Chains of amino acids; act via membrane receptors and second messenger cascades; e.g., ADH, GH, FSH

Steroid Hormones

Derived from cholesterol; lipid-soluble; cross membranes and act via intracellular receptors; e.g., cortisol, aldosterone

Intracellular Hormone Receptors

Bind lipid-soluble hormones; hormone-receptor complex triggers transcription of target genes

Membrane Hormone Receptors

Bind hydrophilic hormones; usually G-protein coupled; activate second messengers like cAMP or Ca²⁺

cAMP Signaling Pathway

Ligand binds receptor → G protein → adenylyl cyclase → cAMP → protein kinase cascade → changes in enzyme/protein activity

Ca²⁺ Signaling Pathway

Ligand activates PLC → PIP2 cleaved into DAG + IP3 → DAG activates PKC, IP3 releases Ca²⁺ from ER → Ca²⁺ binds calmodulin → enzyme activation

Factors Affecting Target Cell Response

Downregulation (fewer receptors if hormone high), upregulation (more receptors if hormone low); hormonal interactions: permissive, synergistic, antagonistic

Feedback Loops

Positive: hormone stimulates more release; Negative: hormone inhibits further release

Humoral & Neural Stimuli

Hormone release regulated by blood component levels (humoral) and nervous system signals (neural)

RTKs Overview

Plasma membrane receptors with intrinsic Tyr kinase activity; signal via phosphorylation of target proteins

INSR Structure & Activation

Dimer of αβ monomers; insulin binding → autophosphorylation of β subunit Tyr residues → activation

IRS1 Signaling

Phospho-Tyr on IRS1 creates docking sites for adaptor proteins → activation of downstream pathways

MAPK Cascade (Mitogenic Pathway)

Ras → Raf → MEK → ERK → transcription factor phosphorylation → regulates gene expression

PI3K-PKB Pathway (Metabolic Pathway)

PI3K → PIP3 → PKB/Akt → glycogen synthesis (via GSK3 inhibition), GLUT4 translocation → ↑ glucose uptake

Cross Talk Between Pathways

INSR signaling can modify GPCR responses (e.g., β-adrenergic receptor) to coordinate metabolism

Key Takeaways

RTKs mediate enzyme-linked receptor signaling; insulin has metabolic effects via PI3K-PKB and growth/gene expression effects via MAPK; amplification, integration, and cross talk are critical; dysregulation → diabetes or cancer