Guyton ch 75

• Neurotransmitters


  Chemicals released from axon terminals that act locally to ascend another nerve impulse
• Endocrine hormones


  Chemical messages released by glands or specialized cells into the circulating blood to affect cells distal to the gland
• Neuroendocrine hormones


  Hormones secreted by neurons that are released into the blood to influence cells elsewhere in the body
• Paracrines


  Chemical messages secreted by cells that affect neighboring cells nearby
• Autocrines


  Chemical messages secreted by cells that automatically influence the cell itself
• Cytokines

  Peptides secreted by cells that can function as autocrines, paracrines or endocrines
• Types of hormones


  • Proteins and polypeptides
  • Steroids
  • Amines (derivatives of amino acid tyrosine)
• Proteins and polypeptides


  • Water-soluble, can be stored within cells, produced as pre-pro-hormones and processed to active form, released via exocytosis in response to stimuli like increased calcium or cAMP
• Steroid hormones


  • Made from cholesterol, lipid-soluble so can enter cells, not stored but synthesized from cholesterol as needed, travel in blood bound to proteins
• Amine hormones


  • Derived from amino acid tyrosine, produced and stored in vesicles, released in response to stimuli
• Hormones are specific for certain receptors, which are only found on certain cells that also have the appropriate intracellular machinery to respond to the hormone</b>
• Increased hormone release


  Triggers negative feedback to reduce hormone release
• There are also positive feedback loops, like luteinizing hormone increasing estrogen, which then further increases luteinizing hormone
• Hormone release is influenced by cyclical variations like seasons, daily cycles, aging, etc.
• Metabolic clearance rate

  Rate of disappearance of hormone from plasma divided by its concentration
• Mechanisms of hormone clearance from plasma

  • Metabolic destruction
  • Binding to tissues
  • Excretion in bile
  • Excretion in urine
• Hormone receptors


  • Can be on cell surface membrane (for water-soluble hormones) or within cell cytoplasm (for lipid-soluble hormones like steroids)
• Metabolic destruction


  Textures bind to tissue, taken up and removed from circulation
• Excretion


  1. By the liver into bile

  2. By the kidneys into urine
• Hormone mechanism of action

  Hormone binds to receptor, which can be on cell surface, in cytoplasm, or in nucleus
• Receptor number


  • Determines hormone sensitivity
  • Down-regulation reduces response
  • Up-regulation increases response
• Receptor binding


  1. Opens ion channel

  2. Activates G protein

  3. Activates enzyme-linked receptor
• G protein-linked receptor


  Transmembrane protein with 7 loops, binds GDP when inactive, GTP when active
• Enzyme-linked receptor

  Receptor is the enzyme, catalyzes a reaction to create a response
• Intracellular hormone receptors


  Lipid-soluble hormones bind, activate promoter sequences in DNA to produce proteins
• Secondary messengers


  Produced after hormone binds receptor, create cascading effects (e.g. cAMP, IP3, DAG, Ca2+/calmodulin)
• cAMP stimulates different effects depending on cell type (e.g. thyroid hormone production, steroid secretion, water permeability)
• IP3 mobilizes calcium, DAG is precursor to inflammatory molecules
• Steroid hormone mechanism


  Hormone binds receptor, complex translocates to nucleus, activates transcription of specific genes, new proteins produced
• Thyroid hormone mechanism


  Hormone enters nucleus, increases transcription of metabolic genes, increases overall cell metabolism