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• Chemical messenger systems


  • Neurotransmitters
  • Endocrine hormones
  • Neuroendocrine hormones
  • Paracrine
  • Autocrine
  • Cytokines
• Neurotransmitters


  • Released by axon terminals of neurons
  • Control nerve cell function
• Endocrine hormones


  • Released by glands or specialized cells into the blood
  • Influence the function of target cells at another location

  
• Neuroendocrine hormones


  • Secreted by neurons into the blood
  • Influence the function of target cells at another location
• Paracrine


  • Secreted by cells into the ECF
  • Affect neighboring target cells of a different type

  
• Autocrine


  • Secreted by cells into the ECF
  • Affect the function of same cells that produce them

  
• Cytokines


  • Peptides secreted by cells into the ECF
  • Can function as autocrine, paracrine or endocrine hormones

  
• General classes of hormones

  • Proteins and polypeptides
  • Steroids
  • Derivatives on the amino acid, tyrosine
• Protein and peptide hormones

  • Synthesized in the rough ER of different endocrine cells
  • Preprohormones first then cleaved to become prohormones
  • Prohormones are sent to the Golgi apparatus for packaging into secretory vesicles
  • Prohormones are cleaved into smaller hormones and stored in cytoplasm
  • Secretion of these hormones are via exocytosis

  
• Increased cytosolic calcium concentration


  Stimulus for exocytosis of protein and peptide hormones
• Stimulation of an endocrine cell surface receptor

  Causes increased cAMP and activation of protein kinases that initiate secretion of the hormone

  
• Peptide hormones


  Water soluble, easily enter the circulatory system
• Steroid hormones


  • Synthesized from cholesterol
  • Lipid soluble
  • Consists of three cyclohexyl rings and one pentyl ring
  • Large stores of cholesterol esters in cytoplasm vacuoles
  • No de novo synthesis because cholesterol is highly lipid soluble

  
• Thyroid hormones


  • Synthesized and stored in the thyroid gland
  • Incorporated into macromolecules of the protein thyroglobulin
  • Secretion occurs when amines are split from thyroglobulin
  • After secretion into the blood, thyroid hormones combine with plasma proteins, thyroxin-binding globulin, which slowly releases the hormones to the target tissue
• Medullary hormones


  • Epinephrine and norepinephrine
  • More epinephrine is secreted
  • Catecholamines are taken up into performed vesicles and stored
  • Released from adrenal medulla via exocytosis

  
• Hormone secretion after a stimulus


  Each different hormone has its own characteristic onset and duration of action
• Epinephrine and norepinephrine


  Secreted within seconds of stimulation
• Thyroxine or growth hormone


  May require months to take full effect
• Rates of secretion of hormones


  Very small
• Negative feedback mechanisms


  • Ensure proper level of hormone activity
  • After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone suppress its further release
  • Controlled variable is sometimes the degree of activity of the target tissue rather than the synthesis or secretory rates of the hormones

  
• Positive feedback


  • Biological action of the hormone causes additional secretion of the hormone
  • Luteinizing hormone (LH) effect of estrogen on the anterior pituitary before ovulation
  • LH acts on ovaries to stimulate additional secretion of estrogen, causes more secretion of LH until negative feedback occurs
• Cyclical variations in hormone release

  • Negative and positive feedback control of hormone secretion are superimposed by periodic variations
  • Seasonal changes
  • Stages of development
  • Aging
  • Daily cycle
  • Sleep
  • Suprachiasmatic nucleus of the hypothalamus serves as a master clock

  
• Water-soluble hormones


  • Peptides and catecholamines
  • Dissolved in plasma and transported to target tissues
  • Diffuse out of capillaries, into the interstitial fluid, to target cells

  
• Steroid and thyroid hormones

  • Circulate in the blood while bound to plasma proteins
  • Protein bound hormones cannot easily diffuse across the capillaries
  • Biologically inactive until disassociation with plasma proteins
• Metabolic clearance rate


  • Milliliters of plasma cleared of hormone per minute
  • Rate of disappearance of hormone from plasma/concentration of hormone
• Hormones are cleared from the plasma


  • Metabolic destruction
  • Binding with tissues
  • Excretion by the liver into the bile
  • Excretion by the kidneys into the urine
• Hormone receptors


  • Hormone binds to specific receptor at the target cell
  • Initiates cascade of reactions in the cell
  • Each stage more powerfully activated
  • Hormone receptors are specific for a single hormone
• Locations for the different types of hormone receptors

  • In or on the surface of the cell membrane for protein, peptide and catecholamine hormones
  • In the cell cytoplasm for steroid hormones
  • In the cell nucleus for thyroid hormones

  
• Down-regulation of the hormone receptor

  • Inactivation of receptor molecules
  • Inactivation of some of the intracellular protein signaling molecules
  • Sequestration of the receptor to the inside of the cell
  • Destruction of the receptors by lysosomes
  • Decreased production of the receptors
• Up-regulation of receptors and intracellular signaling proteins

  • Stimulation of hormone induces greater than normal formation of receptor or intracellular signaling molecules

  
• Ion channel-linked receptors


  • Acetylcholine and norepinephrine combine with receptors in the post synaptic membrane
  • Causing opening or closing a channel for one or more ions
  • Most hormones that do this indirectly by coupling with G-protein linked or enzyme linked receptors

  
• G protein-linked hormone receptors

  • Many hormones activate receptors that indirectly regulate the activity of target proteins by coupling with heterotrimeric guanosine triphosphate (GTP) - binding proteins (G proteins)
  • Parts of a G protein: α, β, and γ subunits
  • Binding of a hormone to the extracellular part

  
• Intracellular protein signaling molecules

  • Sequestration of the receptor to the inside of the cell
  • Destruction of the receptors by lysosomes
  • Decreased production of the receptors

  
• Up-regulation of receptors and intracellular signaling proteins

  • Stimulation of hormone induces greater than normal formation of receptor or intracellular signaling molecules

  
• Ion Channel-Linked Receptors


  Acetylcholine and norepinephrine combine with receptors in the post synaptic membrane, causing opening or closing a channel for one or more ions. Most hormones do this indirectly by coupling with G-protein linked or enzyme linked receptors.

  
• G Protein-Linked Hormone Receptors

  Many hormones activate receptors that indirectly regulate the activity of target proteins by coupling with heterotrimeric guanosine triphosphate (GTP) - binding proteins (G proteins). Binding of a hormone to the extracellular part of the receptor induces signals that open or close cell membrane ion channels, change the activity of the enzyme in the cytoplasm of the cell, or activate gene transcription.

  
• Parts of a G protein

  • α, β, and γ subunits
• Inactive state of G proteins

  α, β, and γ subunits of G proteins form a complex that binds GDP on the α subunit

  
• Active state of G proteins

  1. GDP-bound trimeric G protein associate with the cytoplasmic part of the receptor

  2. Exchange GDP to GTP

  3. Causes the α subunit to disassociate from the trimeric complex and associate with other intracellular signaling proteins

  4. These proteins alter the activity of ion channels or intracellular enzymes such as adenylylcyclase or phospholipase C, which alters the function

  5. Signaling event is terminated when the hormone is removed and the α subunit inactivates itself by converting its bound GTP to GDP

  6. α subunit combines with the β and γ subunits to form an inactive membrane bound trimeric G protein

  
• Gi proteins


  Inhibitory G proteins