Introduction to the Endocrine System

1
Introduction to the Endocrine System

• General Features and Definitions
• Types of Hormones
• Functions of the Endocrine System
• Components of the Endocrine System
• Chemical Structure of Hormones
• Homeostasis
• Endocrine vs. Nervous Systems
• Control of Endocrine Activity
• Regulation of Hormone Secretion
• Transport and Distribution of Hormones
• Mechanism of Hormone Action
• Regulation of Hormone Receptors

2
General Features of the Endocrine System

1. Endocrine glands are ductless
2. Endocrine glands have a rich supply of blood.
3. Hormones, produced by the endocrine glands are
   secreted into the bloodstream.
4. Hormones travel in the blood to target cells
   close by or far away from point of secretion.
5. Hormones receptors are specific binding sites on
   the target cell.

3
Important DefinitionsEndocrine System

• Endocrine--endo means within. This is a system
  which controls body function through hormones.
• Endocrine System is composed of a number of
  glands.
• Glands are specialized tissues that produce a
  hormone or product.

4
Important Definitions

• What are hormones?
• Hormones are organic chemical messengers produced
  and secreted by endocrine cells into the
  bloodstream. Hormones regulate, integrate and
  control a wide range of physiologic functions.

Silverthorn, Human Physiology, 3rd edition Figure
6-12
5
Important Definitions

• What are endocrine glands?
• Endocrine glands are ductless glands comprised of
  endocrine cells. This means that these glands do
  not have ducts that lead to the outside of the
  body. For example, sweat glands are NOT
  endocrine glands (they are instead exocrine
  glands) because sweat glands have ducts that lead
  to the outside surface of your skin (thats how
  the sweat gets out). The fact that endocrine
  glands are ductless means that these glands
  secrete hormones directly into the blood stream
  (instead of to the outside of your body).

6
Important Definitions

• What are target cells?
• Target cells refer to cells that contain specific
  receptors (binding sites) for a particular
  hormone. Once a hormone binds to receptors on a
  target cell, a series of cellular events unfold
  that eventually impact gene expression and
  protein synthesis.

Silverthorn, Human Physiology, 3rd edition Figure
6-12
7
Important Definitions

• What are hormone receptors?
• Hormone receptors are binding sites on the target
  cell (either on the surface or in the cytoplasm
  or nucleus of the target cell) that are activated
  only when specific hormones bind to them. If a
  hormone does not/cannot bind to its receptor,
  then no physiologic effect results.

See next slide for a picture of a hormone bound
to its receptor
8
Growth hormone regulates cell growth by binding
to growth hormone receptors on target cells.
9
Types of Hormones

• Steroid Hormones
• These are all derived from cholesterol.
• Examples testosterone, estrogen, progesterone,
  mineralicoids, glucocorticoids.
• Steroids can cross the plasma membrane!
• Other kinds of lipids.

• Protein Hormones
• These are made of amino acids.
• Examples Insulin, hypothalmus-signaling
  hormones.
• Protein hormones cannot cross the plasma membrane!

10
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.

11
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

12
Examples of Lipid-Soluble Hormones

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

13
Classes of Hormones

• Steroids vs. Peptide Hormones
• Hormones fall into 2 general classes based on
  their molecular structure and synthesis.
• All steroid hormones are made initially from the
  precursor (precursor first step in biosynthetic
  pathway) cholesterol.

See next slide for a diagram of the biosynthetic
pathway of steroid hormones from cholesterol.
14
(No Transcript)
15
Steroid Hormones

• Steroid hormones are produced by the gonads and
  adrenal cortex.
• Thyroid hormones are not steroids, but will be
  categorized with steroids for simplicity.
• Steroid hormones are made from cholesterol in the
  smooth endoplasmic reticulum and mitochondria of
  endocrine cells.

16
Steroid Hormones

• Steroid hormones cannot be stored in vesicles in
  the endocrine cells that produce them. As soon as
  steroid hormones are produced, they diffuse out
  of the endocrine cell and enter the bloodstream.
• Steroid hormones are lipid soluble and their
  receptors are located inside their target cell.

17
(No Transcript)
18
Peptide Hormones

• Peptide hormones are comprised of chains on amino
  acids.
• Like most proteins, peptide hormones are
  synthesized on ribosomes of the (rough)
  endoplasmic reticulum of endocrine cells.
• Peptide hormones can be stored in vesicles in
  endocrine cells until they are needed at some
  later point.

19
Peptide Hormones

• Peptide hormones do not readily pass through cell
  membranes (lipid bilayers) and they are referred
  to as water soluble.
• Receptors for peptide hormones are found on the
  cell surface of their target cells.

20
(No Transcript)
21
Some General Actions of Hormones

• Hormones cause cells to change.
• Hormones can result in changes in gene expression
  (DNA-RNA-Protein).
• Hormones can result in enzyme cascades which
  control our metabolism.
• Hormones drive our reproductive systems.

22
Some Specific Actions of Hormones

• Fetal development and differentiation
• Cell growth and cancer
• Metabolism
• Cardiovascular function
• Renal function
• Skeletal function
• Reproductive function
• Immune function
• Central nervous system function

23
(No Transcript)
24
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).

25
(No Transcript)
26
(No Transcript)
27
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
28
Another Example of Homeotasis Regulation of
Blood pH Levels
Blood pH
7.5 7.3
29
Feedback control

• Negative feedback is most common for example, LH
  from pituitary stimulates the testis to produce
  testosterone which in turn feeds back and
  inhibits LH secretion
• Positive feedback is less common examples
  include LH stimulation of estrogen which
  stimulates LH surge at ovulation

30
Negative feedback effects of cortisol
31
Substrate-hormone control

• Glucose and insulin as glucose increases it
  stimulates the pancreas to secrete insulin

32
Feedback control of insulin by glucose
concentrations
33
(No Transcript)
34
Endocrine overview

• Hormones are released by glands.
• Hormones are released by feedback.
• Our body works to carefully regulate hormone
  levels.
• Negative feedback usually controls hormone
  secretion.

35
Homeostasis and Controls

• Successful compensation
• Homeostasis reestablished
• Failure to compensate
• Pathophysiology
• Illness
• Death

Figure 1-5 Homeostasis
36
Feedback Loops
Figure 6-26 Negative and positive feedback
37
Negative Feedback Controls Long Short Loop
Reflexes
38
Endocrine Reflex Pathways Overview
39
Pathologies Over or Under Production
40
Pathologies Due to Receptors
41
Endocrine vs. Nervous System

• Major communication systems in the body
• Integrate stimuli and responses to changes in
  external and internal environment
• Both are crucial to coordinated functions of
  highly differentiated cells, tissues and organs
• Unlike the nervous system, the endocrine system
  is anatomically discontinuous.

42
Nervous system

• The nervous system exerts point-to-point control
  through nerves, similar to sending messages by
  conventional telephone. Nervous control is
  electrical in nature and fast.

43
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)

44
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).

45
Hormones travel via the bloodstream to target
cells

• The endocrine system broadcasts its hormonal
  messages to essentially all cells by secretion
  into blood and extracellular fluid. Like a radio
  broadcast, it requires a receiver to get the
  message - in the case of endocrine messages,
  cells must bear a receptor for the hormone being
  broadcast in order to respond.

46
A cell is a target because is has a specific
receptor for the hormone
Most hormones circulate in blood, coming into
contact with essentially all cells. However, a
given hormone usually affects only a limited
number of cells, which are called target cells. A
target cell responds to a hormone because it
bears receptors for the hormone.
47
Principal functions of the endocrine system

• Maintenance of the internal environment in the
  body (maintaining the optimum biochemical
  environment).
• Integration and regulation of growth and
  development.
• Control, maintenance and instigation of sexual
  reproduction, including gametogenesis, coitus,
  fertilization, fetal growth and development and
  nourishment of the newborn.

48
Types of cell-to-cell signaling
Classic endocrine hormones travel via bloodstream
to target cells neurohormones are released via
synapses and travel via the bloostream paracrine
hormones act on adjacent cells and autocrine
hormones are released and act on the cell that
secreted them. Also, intracrine hormones act
within the cell that produces them.
49
Response vs. distance traveled
Endocrine action the hormone is distributed in
blood and binds to distant target
cells.Paracrine action the hormone acts locally
by diffusing from its source to target cells in
the neighborhood.Autocrine action the hormone
acts on the same cell that produced it.
50
Major hormones and systems

• Top down organization of endocrine system.
• Hypothalamus produces releasing factors that
  stimulate production of anterior pituitary
  hormone which act on peripheral endocrine gland
  to stimulate release of third hormone
• Specific examples to follow
• Posterior pituitary hormones are synthesized in
  neuronal cell bodies in the hypothalamus and are
  released via synapses in posterior pituitary.
• Oxytocin and antidiuretic hormone (ADH)

51
Regulation of hormone secretion

• Sensing and signaling a biological need is
  sensed, the endocrine system sends out a signal
  to a target cell whose action addresses the
  biological need. Key features of this stimulus
  response system are
•         receipt of stimulus
•         synthesis and secretion of hormone
•         delivery of hormone to target cell
•         evoking target cell response
•         degradation of hormone

52
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
53
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
54
Some Specific Types of Chemical Signaling

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

55
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

56
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

57
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

58
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)

59
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

60
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

61

Patterns of Secretion
Pulsatile
Acute
Cyclic
62
Cyclic Increases in Reproductive Hormones
Rat Ovulatory Cycle
LH
E2
Hormone Level
FSH
Diestrus Diestrus
Proestrus
Estrus
Day 1
Day 2
63
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)

64
Where are Hormones Distributed to?

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

65
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
66
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.

67
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.

68
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).

69
What Receptors Do

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

70
Types of Membrane-Bound Receptors
71
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
72

Types of Receptors (the other kind)

• 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
73
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.
• More about receptors in the next lecture

74
Next Lecture..

• Hormone Survey