Endocrine System

• Endocrine system


  A body control system that interacts with the nervous system to coordinate and integrate the activity of body cells
• Endocrinology


  Study of hormones and endocrine organs

  
• Hormone


  Chemical messengers released into extracellular fluids and blood by glands, transported throughout the body, bind their cellular receptors, initiate a biological response

  
• Hormone response


  • Occurs after a lag period (seconds to days)
  • Responses are prolonged (for long periods)
  • Responses are widespread and diverse (most body cells respond to hormone release)
• Autocrines


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


  • Prostaglandins: released by smooth muscle cells, induce smooth muscles cell contraction
• Paracrines


  Act locally but affect cell types other than those releasing the paracrine chemicals
• Paracrines


  • Somatostatin: released by one population of pancreatic cells, inhibits release of insulin by a different population of pancreatic cells
• Processes controlled and integrated by hormones


  • Reproduction
  • Growth and development
  • Maintenance of electrolyte balance of blood
  • Maintenance of water balance of blood
  • Maintenance of nutrient balance of blood
  • Regulation of cellular metabolism and energy balance
  • Mobilization of body defenses
• Endocrine tissue and organs

  • Not grouped together like other systems, but rather scattered throughout body
  • Endocrine glands produce hormones and lack ducts (ductless glands)
  • Release hormones into surrounding tissue fluids
  • Typically have a rich vascular and lymphatic drainage that receives the hormones
  • Most of hormone-producing cells are arranged in cords and branching networks

  
• Chemical classes of hormones


  • Amino acid-based that vary in molecular size (simple aa derivatives, peptides, proteins)
  • Steroids (synthesized from cholesterol)
• Eicosanoids


  Biologically active lipids made from arachidonic acid, typically highly localized, affect only nearby cells, do not fit the definition of true hormones

  
• Types of eicosanoids


  • Leukotrienes (mediate inflammation and some allergic reactions)
  • Prostaglandins (have multiple targets and effects, raise blood pressure, increase expulsive uterine contraction of birth, enhance blood clotting, enhance pain and inflammation)

  
• Mechanisms of hormone action

  • Secreted hormones circulate to virtually all tissue but will only influence their target cells
  • Hormones alter the cell activity, either decrease or increase the rate of normal cellular processes
  • Precise response depends on target cell type

  
• Mechanisms of hormone action


  • Epinephrine: blood vessels - contraction of smooth muscles, liver - stimulates glycogenolysis

  
• Ways a hormonal stimulus can cause


  • Alteration in plasma membrane's permeability
  • Alteration in plasma membrane's potential
  • Stimulation of synthesis of protein or regulatory molecules (e.g. enzymes) within the cell
  • Activation or deactivation of enzymes
  • Induction of secretory activity
  • Stimulation of mitosis

  
• Ways hormones act on their receptors

  • Water-soluble hormones (all aa hormones except thyroid hormone) act on receptors in plasma membrane (G protein-coupled receptors, intracellular signals include second messenger molecules)
  • Lipid-soluble hormones (steroid and thyroid hormones) act on intracellular receptors (directly activates genes)

  
• cAMP signalling mechanism


  1. Hormone binds its receptor on plasma membrane

  2. Receptor activates G protein

  3. G Protein activates adenylate cyclase

  4. Active Adenylate cyclase converts ATP to cyclic AMP

  5. cAMP activates protein kinase A (PKA)

  
• PIP2-Calcium signalling mechanism


  1. Hormone binds its receptor on plasma membrane

  2. Receptor activates Gq protein

  3. Gq protein activates phospholipase C (PLC)

  4. PLC cleaves phosphatidyl insositol bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3)

  5. Ca++ acts as a secondary messenger, binds & activates calmodulin

  
• Other signaling mechanisms


  • Some hormones use cyclic guanosine monophosphate (cGMP) as a second messenger
  • Some hormones and growth factors work without second messengers (e.g. insulin receptor is a tyrosine kinase enzyme)
  • Changes in intracellular Ca++ can be one of the methods of intracellular transduction and effector mechanisms

  
• Intracellular receptors and direct gene activation


  1. Lipid soluble hormones (steroid hormones) diffuse into target cells, bind and activate intracellular receptor

  2. Activated receptor-hormone complex translocates to the nucleus, binds its hormone response element on the DNA

  3. Turns on a gene, prompts DNA transcription to produce mRNA

  4. mRNA is translated by cytoplasmic ribosomes into protein molecules

  
• Intracellular receptors


  • In absence of hormone, receptors bind chaperon proteins, keep receptors from binding to DNA and protect receptors from proteolysis
  • When hormone is present, complex dissociates
  • Thyroid hormone receptor is ALWAYS bound to DNA even in absence of thyroid hormone

  
• Target cell specificity


  • The possession of a specific cellular hormone receptor defines a target cell
  • Target cells can be a limited population of cells or a broad type of cells in multiple body locations
  • Target cell activation depends on blood levels of the hormone, relative number of hormone receptors on/in cell, and affinity of binding between the hormone and the receptor

  
• Target cell response


  • Target cells may up-regulate the hormone receptor expression in response to increased hormone blood levels
  • Persistence of high hormonal levels may lead to target cell down-regulate its receptor expression, cell becomes desensitized
  • Hormones may also influence number & affinity of receptors that respond to other hormones

  
• Half-life


  The length of time for a hormone's blood level to decrease by half, from fraction of a minute up to a week, water-soluble hormones < lipid-soluble hormones
• Onset and duration of hormone activity


  • Time required for hormone effects varies greatly, immediate responses (mostly water-soluble hormones), delayed (hours/days) responses (mostly steroid hormones)
  • Duration of hormone action is limited, ranges from 10 seconds to several hours depending on hormone
  • Hormonal blood levels must be precisely and individually controlled to meet the continuously changing needs of the body
• Interaction of hormones at target cells


  • Permissiveness: one hormone cannot exert its full effect without presence of another hormone
  • Synergism: hormones with similar effects on target cell combine to amplify the effect
  • Antagonism: one hormone opposes the action of another

  
• Control of hormone release


  • Synthesis and release of most hormones are regulated by some type of negative feedback system
  • Hormone release is controlled via stimulation of endocrine gland, and further modulated by the nervous system

  
• Stimuli that trigger endocrine glands to release hormones


  • Humoral (body fluids)
  • Neural
  • Hormonal

  
• Humoral (body fluids) stimuli


  Some endocrine glands release their hormones in direct response to changing blood levels of certain critical ions and nutrients

  
• Humoral stimuli


  • Parathyroid glands secrete parathyroid hormone (PTH) in response to blood Ca++ levels, insulin by the pancreas, and aldosterone by the adrenal cortex

  
• Neural stimuli


  Nerve fibers stimulate hormone release

  
• Neural stimuli


  • Sympathetic nervous stimulation of the adrenal medulla to release catecholamines (norepinephrine and epinephrine) during periods of stress

  
• Hormonal stimuli


  Many endocrine glands release their hormones in response to hormones produced by other endocrine organs, promotes rhythmic hormone release

  
• Hormonal stimuli


  • Release of most anterior pituitary hormones is regulated by releasing (or inhibiting) hormones produced by the hypothalamus, many anterior pituitary hormones in turn stimulate other endocrine organs to release their hormones

  
• Humoral stimuli


  Blood levels of certain critical ions and nutrients
• Humoral stimuli


  • Parathyroid gland secreting parathyroid hormone (PTH) in response to blood Ca++ levels

  
• PTH response to blood Ca++ levels

  1. PTH increases Ca++ by different mechanisms

  2. Ends the initiative (stimulus) for PTH release

  
• Humoral stimuli


  • Insulin by the pancreas
  • Aldosterone by the adrenal cortex
• Neural stimuli


  Nerve fibers stimulating hormone release