Introduction to the Endocrine System

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Introduction to the Endocrine System

• Homeostasis
• Functions of the Endocrine System
• Components of the Endocrine System
• Chemical Structure of Hormones
• Regulation of Hormone Secretion
• Transport Distribution of Hormones
• Mechanism of Hormone Action
• Regulation of Hormone Receptors

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Characteristics of Living Things

• Maintaining boundaries to separate the internal
  from the external environments.
• Cellular level cell membrane
• Organism level integumentary system (skin)
• Organ level pericardium (heart), DAP mater for
  brain, stratum corneum for skin.
• Movement.
• Skeletal and muscular system responsibilities and
  functions.
• Digestive system to move food stuffs
  peristalsis.
• C.V. system to move blood, gas exchange.
• Urinary system to move urine.
• Cellular level contractility of individual
  cells.

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Characteristics of Living Things (contd)

• Responsiveness or Irritability Ability to sense
  changes in the environment then respond to them.
  e.g., CNS withdrawal reflex.
• Digestion breaking down ingested foodstuffs to
  single molecules.
• - accomplished by entire multicellular
  organisms or single-cellular organisms.

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Characteristics of Living Things (contd)

• Metabolism Occurs at the cellular level.
• Catabolism breaking down substances to simpler
  compounds.
• Anabolism Using these simple catabolic products
  to produce energy (ATP).
• Depends on the digestive and C.V. systems to make
  nutrients and O2 available to the blood and then
  to distribute these throughout the body.
• Regulated by hormones secreted by the endocrine
  gland systems.
• Excretion Process of removing waste from the
  body e.g., indigestible food in feces, N2 excess
  in urine, CO2 in cellular respiration ? lungs ?
  expired air.

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Characteristics of Living Things (contd)

• Reproduction
• Cells mitosis or meiosis
• Organism egg sperm ? baby
• Reproductive system produces offspring, but its
  function is regulated by hormones of the
  endocrine system.
• Growth
• Increase size of a body part of organisms or
  individual cells (e.g., muscles)
• For growth to occur, constructive (anabolic)
  activities must occur more quickly than
  destructive (catabolic) ones.

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Homeostasis

• Definition the maintenance of a constant
  environment (internal).
• Parameters regulated Temperature, osmolarity,
  pH, nutrient levels, hormone levels, etc.
• Homeostasis is critical for cell viability and
  proper functioning.
• Loss of homeostasis results in disease/death.
• Homeostasis is maintained by feedback mechanisms
  (primarily negative feedback).

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Example Regulation of Blood pH Levels
Blood pH
7.5 7.3
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Functions of the Endocrine System

• Contributes to and interacts with the control and
  integration functions of the nervous system
• Important in the maintenance of homeostasis (set
  points), usually through negative feedback
• Occasionally involved in processes with
  controlled movement away from set point (positive
  feedback)

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Why Two Systems? Comparison of Nervous and
Endocrine Systems

• The nervous system responds to changes in the
  environment quickly, the endocrine system more
  gradually.
• The effects of nervous system action are
  short-lived, while the effects of endocrine
  changes persist longer.
• The nervous signal (neurotransmitter) is highly
  localized (at the synapse), the endocrine signal
  (hormone secretion) is systemic.
• The magnitude of nervous system effects are
  dependent upon the frequency of action potentials
  (frequency modulated) the magnitude of endocrine
  effects are dependent upon the amount of hormone
  released (amplitude modulated).

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So, why two systems?

• Both maintain homeostasis.
• The nervous system regulates functions that can
  change extremely rapidly.
• The endocrine system regulates functions that
  change over longer time spans.
• Some functions are regulated by both systems.

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Components of the Endocrine System Some
Definitions

• Hormone secretory product of endocrine gland,
  which is released into the general circulation
  and acts at some distant site on a target
  cell/organ.
• Endocrine glands ductless glands which produce
  hormones
• Target Cell Cell which is capable of responding
  to the hormone, due to the presence of hormone
  receptors in that cell.
• Receptor binds hormone, resulting in a
  biological response

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Some Specific Types of Chemical Signaling

• Hormones chemicals released into the blood
  stream, act at a distant site
• Autocrine factor chemical signal is released
  from a cell type, and acts upon that same cell
  type

chemical
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Some Specific Types of Chemical Signaling

• Paracrine factor chemical is released from one
  cell type, and acts locally on another cell type
  (in same tissue)

chemical
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Some Specific Types of Chemical Signaling

• Pheromone chemical is released into the
  environment, can affect other individuals

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Some Specific Types of Chemical Signaling

• Neurotransmitter chemical released into synaptic
  cleft, influences postsynaptic cell
• Neurohormone chemical released from neuron into
  bloodstream, acts at distant site

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Chemical Structure of Hormones

• Two general classes of hormones water soluble
  and lipid soluble.
• Water soluble (polar) proteins, glycoproteins,
  polypeptides, amino acid derivatives.
• Lipid soluble (nonpolar) steroids, amino acid
  derivatives, fatty acids.
• Different classes have different mechanisms of
  action, different modes of transport through the
  body, and differing stability in the circulation.

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Examples of Water Soluble Hormones

• Proteins growth hormone, prolactin, insulin
• Glycoproteins follicle-stimulating hormone
  (FSH), luteinizing hormone (LH) ,
  thyroid-stimulating hormone (TSH)
• Polypeptides arginine vasopressin, oxytocin,
  somatostatin
• Amino acid derivativesepinephrine, melatonin

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Examples of Lipid Soluble Hormones

• Steroids estrogen, progesterone, testosterone,
  glucocorticoids, mineralocorticoids
• Amino acid derivatives Thyroid hormones (T3, T4)
• Fatty acids prostaglandins, thromboxanes

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What determines the size of hormone effects?

• 1) The amount of hormone in the circulation
  (reaching the target tissue)
• - the more hormone, the greater the effect
• 2) The presence and number of receptors for that
  hormone on the target tissue.
• - no receptor, no response
• - some receptors, some response
• - many receptors, higher response

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How do you regulate hormone levels?

• Hormones are generally not secreted at a constant
  rate.
• Regulation of hormone levels involves
• - regulation of hormone production
• - regulation of hormone secretion (often a
  separate step)
• - sometimes, regulation of hormone metabolism

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Mechanisms of Hormone Regulation

• Neural Regulation neurons synapse with cells
  producing hormone (ie, norepinephrine release
  from the adrenal gland).
• Endocrine Regulation hormones bind to endocrine
  cells, regulating release of another hormone (ie,
  FSH stimulates estrogen release)
• Regulation by other factors (humoral) endocrine
  cells respond to levels of other factors in the
  circulation (ie, glucose causes increased insulin
  secretion from the pancreas)

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Role of Feedback in Secretion

• The secretion of hormones is usually dependent
  upon feedback mechanisms
• Negative feedback a stimulus causes an endocrine
  response (hormone secretion) which will decrease
  the level of that stimulus
• Positive feedback a stimulus causes a response
  which will increase the level of that stimulus

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Example of Negative Feedback Regulation of Blood
Glucose Levels

• Increase in stimulus leads to decrease in the
  intensity of the stimulus (return to set point).
• Stimulus being monitored blood glucose
  concentrations
• After a meal is digested, blood glucose levels
  increase
• The increase in blood glucose is detected by the
  pancreas
• The pancreas releases insulin, which decreases
  blood glucose levels
• Decreased blood glucose levels result in
  decreased insulin release

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Regulation of Blood Glucose Levels
Food
Increased blood glucose
increased insulin release
decreased insulin release
decreased blood glucose
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Another Example Regulation of LH Release in the
Male

• LH increases production of testosterone from the
  testis.
• Testosterone feeds back upon the pituitary to
  inhibit LH release.

(-)
testosterone
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Example of Positive Feedback (rare)

pressure on uterus
uterine contraction
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Patterns of Hormone Secretion

• There are three basic patterns of secretion
  pulsatile, acute, and cyclic.
• Pulsatile relatively constant level of hormone,
  over a long period
• Acute rapid increase in hormone level for a
  short time in response to a stimulus
• Cyclic hormone increases and decreases in a
  constant pattern

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Patterns of Secretion

Pulsatile
Acute
Cyclic
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Cyclic Increases in Reproductive Hormones
Rat Ovulatory Cycle
LH
E2
Hormone Level
FSH
Diestrus Diestrus
Proestrus
Estrus
Day 1
Day 2
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How are hormones transported through the body to
their target cells?

• Some hormones are bound to proteins (binding
  proteins) in the bloodstream
• hormone binding protein lt----gt complex
• - hormone must unbind to act on tissues binding
  affects activity of hormone
• - binding proteins may increase the time the
  hormone stays in the circulation
• -some binding proteins highly specific, some
  less specific
• Other hormones circulate freely in the blood (no
  binding proteins)

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Where are Hormones Distributed to?

• Hormones are distributed in the general
  circulation to all parts of the body that receive
  blood flow.

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What is a half-life?

• Hormones are eventually broken down (metabolized)
  and/or excreted from the body.
• The rate of removal from the circulation is
  fairly constant for a given hormone.
• The length of time it takes to remove half of the
  amount of hormone from the circulation is the
  half-life of that hormone.

100
50
Amount of Hormone
0
Time
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What is a half-life?

• In general, water-soluble hormones have shorter
  half-lives than lipid soluble hormones (rapid
  degradation in kidney, liver, lungs)
• Hormones with short half-lives exhibit rapid
  changes in hormone levels.

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Conjugation of Hormones

• Some hormones (ie, steroids) are modified by the
  liver (conjugation).
• Water-soluble groups are added on (sulfate,
  glucuronic acid),decreasing activity and
  increasing the water solubility of the hormone.
• Increasing water solubility increases the rate at
  which the hormone is excreted by the kidney.

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Mechanism of Hormone Action Receptors

• For hormones to act on a cell, that cell must
  have a receptor for that hormone.
• Receptors bind the hormone, resulting in a
  biological response.
• Receptors are found only in target tissues for
  that hormone.
• Receptors are very specific (they only bind a
  specific hormone, not all hormones)
• Receptors have high affinity for their hormone
  (bind hormone at very low hormone concentration).

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What Receptors Do

• Activate second messenger systems (cyclic AMP,
  cyclic GMP).
• Phosphorylate cellular proteins, affecting their
  activity.
• Control ion channels.
• Regulate gene transcription.

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Types of Receptors

• Membrane Bound For hormones which do not enter
  the cell, the receptor is on the surface of the
  cell membrane. These typically affect second
  messengers, kinases, and ion channels.

FSH
protein kinase A
FSH
cAMP
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Types of Receptors

• Intracellular Receptor Steroid hormones, thyroid
  hormone, and vitamin D cross the plasma membrane
  and bind to receptors within the cell. This
  hormonereceptor complex binds DNA, regulating
  gene expression.

E2
E2RDNA
E2R
,-
mRNA
protein
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Regulation of Receptors

• The responsiveness of a target cell to a hormone
  is dependent upon the number of receptors
  present.
• By increasing or decreasing receptor number, you
  can regulate the hormonal activity on the target
  cell.
• Up-regulation increase in receptor number due to
  increased synthesis.
• Down-regulation decrease in receptor number due
  to decreased synthesis and/or increased
  degradation.

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Next Lecture..

• Hormone Chemistry