Endocrine real

• Hormone


  A chemical signal that is secreted into the circulatory system and communicates regulatory messages within the body
• Hormones


  • May reach all parts of the body
  • Only certain types of cells, target cells, are equipped to respond
• Hormone


  A chemical substance released by a group of cells to control the function of other types of cells
• Types of hormones


  • Affect many different types of cells (e.g. GH and Thyroxin)
  • Affect only specific target cells (e.g. ACTH and estrogen)
• Nervous system


  Conveys high-speed electrical signals along specialized cells called neurons
• Endocrine system

  Made up of endocrine glands that secrete hormones to coordinate slower but longer-acting responses to stimuli
• The endocrine and nervous systems


  Often function together in maintaining homeostasis, development, and reproduction
• Neurosecretory cells


  Specialized nerve cells that release neurohormones into the blood
• Endocrine hormones and neurohormones

  Function as long-distance regulators of many physiological processes
• Major human endocrine glands

  • Hypothalamus
  • Pineal gland
  • Pituitary gland
  • Thyroid gland
  • Parathyroid glands
  • Adrenal glands
  • Pancreas
  • Ovary (female)
  • Testis (male)
• The multiple hormone systems play a key role in regulating almost all body functions: metabolism, growth and development, water and electrolyte balance, reproduction, and behavior
• Target cells


  Cells that contain specific receptors (binding sites) for a particular hormone
• Autocrines


  Chemicals that exert their effects on the same cells that secrete them
• Paracrines


  Locally acting chemicals that affect cells other than those that secrete them
• Autocrines and paracrines are not considered hormones since hormones are long-distance chemical signals
• Three major classes of molecules that function as hormones in vertebrates

  • Proteins and peptides
  • Amines derived from amino acids
  • Steroids
• Types of Amino Acid Based Hormones

  • Amines (Tyrosine: Caecholamines and Thyroid hormones, Tryptophan: Melatonin)
  • Polypeptide hormones
  • Protein hormones
• Steroid Hormones


  Derived from cholesterol, secreted by gonads, adrenals, placenta
• Fatty Acid Derived Hormones

  Eicosanoids, derived from arachidonic leukotrienes and prostaglandins
• Peptide (Protein) Hormone Synthesis

  1. Synthesized as preprohormone

  2. Post-translational modification to prohormone

  3. Then hormone
• Steroid Hormones


  • Lipophilic, cross membranes (no storage), on-demand synthesis (SER), usually bound to carrier proteins
• Amine Hormones


  • Tryptophan: Melatonin
  • Tyrosine: Catecholamines (behave like peptide hormones)
  • Tyrosine: Thyroid hormones (behave like steroid hormones)
• Hormonal Receptors


  • Large proteins, 2000-100,000 receptors/cell, highly specific for a single hormone
• Receptor Locations


  • On the surface of cell membrane (proteins, peptides and catecholamines)
  • In the cell cytoplasm (Steroids)
  • In the cell nucleus (thyroid hormones)
• Mechanism of Peptide and Protein Hormone Action

  1. Hormone (first messenger) binds to receptor

  2. Receptor binds to G protein

  3. G protein binds GTP, displacing GDP

  4. Activated G protein activates adenylate cyclase

  5. Adenylate cyclase generates cAMP (second messenger) from ATP

  6. cAMP activates protein kinases, causing cellular effects
• Cell Membrane Phospholipid: Second Messenger System

  1. Hormone binds to receptor and activates G protein

  2. G protein binds and activates a phospholipase enzyme

  3. Phospholipase splits PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers)

  4. DAG activates protein kinases; IP3 triggers release of Ca2+ stores

  5. Ca2+ (third messenger) alters cellular responses
• Tyrosine Kinase System Second Messenger

  1. Used by insulin & many growth factors to cause cellular effects

  2. Surface receptor is tyrosine kinase: consists of 2 units that form active dimer when insulin binds

  3. Activated tyrosine kinase phosphorylates signaling molecules

  4. Induction of hormone/growth factor effects
• Steroid and Thyroid Hormone Mechanism of Action

  1. Hormone diffuses into target cell

  2. Binds and activates intracellular receptor

  3. Hormone-receptor complex travels to nucleus and binds DNA-associated receptor protein

  4. This interaction prompts DNA transcription to produce mRNA

  5. mRNA is translated into proteins, which bring about cellular effect
• Downregulation


  Increase in hormone concentration leads to decrease in the number of active receptors
• Upregulation


  The hormone induces greater than normal formation of a receptor or intracellular signaling proteins
• Determinants of Free Hormone Receptor Binding

  • Carrier-bound hormone
  • Free hormone
  • Hormone receptor
  • Hormone degradation
  • Biological effects
• Blood Levels of Hormones

  • Controlled by negative and positive feedback systems
  • Vary only within a narrow desirable range
  • Hormones are synthesized and released in response to humoral, neural, and hormonal stimuli
• Hormone Concentrations in the Blood

  • Hormones circulate in the blood in free or bound form
  • Steroids and thyroid hormone are attached to plasma proteins
• Factors Affecting Hormone Concentrations in the Blood

  • Rate of release
  • Speed of inactivation and removal from the body
  • Hormones are removed from the blood by degrading enzymes, the kidneys, and liver enzyme systems
• Transport of Hormones


  • Water soluble hormones dissolved in plasma
  • Fat soluble hormones transported bound to plasma proteins (90%), binding helps provide reservoirs and slow clearance
• Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with Degree of Protein Binding
• Circulating Transport Proteins


  • Specific: Corticosteroid binding globulin, Thyroxine binding globulin, Sex hormone-binding globulin
  • Nonspecific: Albumin, Transthyretin (prealbumin)
• Negative feedback


  Regulates many hormonal pathways involved in homeostasis
• Positive feedback


  Less common, examples include LH stimulation of estrogen which stimulates LH surge at ovulation
• Feedback Control Pathways


  Stimulus -> Receptor -> Endocrine cell -> Blood vessel -> Target effectors -> Response (Negative Feedback)

  Stimulus -> Sensory neuron -> Hypothalamus/posterior pituitary -> Neurosecretory -> (Positive Feedback)