6. Major control systems of body
1. Nervous system
2. Endocrine system

7. • The endocrine system is the system of glands,
each of which secretes different types of
hormones
directly into the bloodstream (
some of which are transported along nerve
tracts)
to regulate the body.

8. Word meaning
• The endocrine system is in contrast to the
exocrine system,
• which secretes its chemicals using ducts.
• It derives from the Greek words "endo"
meaning inside, within, and "crinis" for
secrete.

9. • The endocrine system is an information signal
system
• like the nervous system,
• yet its effects and mechanism are classifiably
different.
• The endocrine system's effects are
• slow to initiate, and
• prolonged in their response,
• lasting from a few hours up to weeks.

10. • The nervous system sends information very
quickly, and responses are generally short
lived.
• Hormones are substances (chemical
mediators) released from endocrine tissue
• into the bloodstream
• where they travel to
• target tissue and generate a response.

11. • Hormones regulate various human
functions, including
• metabolism,
• growth and
• development,
• tissue function,
• and mood.

12. Glands
Introduction

13. • In addition to the specialised endocrine
organs mentioned above, many other organs
that are part of other body systems, such as
the kidney, liver, heart and gonads, have
secondary endocrine functions.
• For example the kidney secretes endocrine
hormones such as erythropoietin and renin.

14. • The endocrine system is made of a series of
glands that produce chemicals called
hormones.
• A number of glands that signal each other in
sequence are usually referred to as an axis, for
example, the hypothalamic-pituitary-adrenal
axis.

18. How CNS works…
• The multiple activities of the cells, tissues, and
organs of the body are coordinated by the
interplay of several types of chemical
messenger systems:
• Neurotransmitters are released by axon
terminals of neurons into the synaptic
junctions and act locally to control nerve cell
functions.

21. Cortical neuron stained with antibody to neurofilament subunit NF-L in green.
In red are neuronal stem cells stained with antibody to alpha-internexin.
Image created using antibodies from EnCor Biotechnology Inc

24. • CNS works through • Endocrine system works
Neuron through Hormones
• Within milliseconds • Seconds to hours or
days
• Direct, fast • Indirect and far
• Muscles, glands, cells • Cells of body
• Briefer action generally • Longer action generally

25. Hormones
1. How they works?
2. Chemical classification

26. Word meaning
• Get moving or excite
• It is the mediator that is released in one part
of the body but regulates the activity of cells
in other parts of the body.

27. • Endocrine hormones are released by glands or
specialized cells into the circulating blood and
influence the function of cells at another
location in the body.

28. • Only the target cells have receptors that bind
and recognize that hormone.
• For example, thyroid stimulating hormone TSH
binds to receptors on cells of thyroid
gland, but it does not bind to cells of the
ovaries.

29. Receptors and Target cells

30. • Receptors, like other
cellular protein, are
constantly
synthesized and
broken down.
• Generally, a target
cell has 2,000 to
1,00,000 receptors for
a particular hormone.

31. • If a hormone is present in excess, the number
of target-cell receptors may decrease
• This effect is known as DOWN REGULATION.
• E.G. when certain cells of the testes are
exposed to a high concentration of luteinizing
hormone (LH) the number of LH receptors
decreases.

32. • Down regulation make the cell LESS SENSITIVE
to a hormone.

33. • In contrast, when a hormone is deficit, the
number of receptors may increase.
• This phenomenon is know as UP REGULATION.
• It makes the target cell more sensitive to a
hormone.

35. Application
• Drug RU486 mifepristone used for abortion
• It binds the receptors for progesterone and
prevents it from exerting its normal effect.
• So no preparation of lining of the uterus for
implantation.

36. Circulation of Hormones

37. Variety
circulatory hormone & Local hormone

38. • Neuroendocrine hormones are secreted by
neurons into the circulating blood and
influence the function of cells at another
location in the body.

39. • Paracrines are secreted by cells into the
extracellular fluid and affect neighbouring
cells of a different type.
• Autocrines are secreted by cells into the
extracellular fluid and affect the function of
the same cells that produced them by binding
to cell surface receptors.

42. • One example of local hormone is interleukin 2.
• It is released by helper T cells (WBC)
• During immune response, IL-2 helps activating
other nearby immune cells, a paracrine effect.
• But it also act as autocrine by stimulating the
same cell.
• This action makes more secretion of IL-2
again.
• Thus strengthen the immune response.

43. • Local hormone used to inactivated quickly;
circulating hormones may linger in the blood
and exert their effects for a few minutes or
occasionally for a few hours.
• In time, circulating hormones are inactivated
by the liver and excreted by kidneys.
• In cases of kidney or liver failure, excessive
levels of hormones may build up in the blood.

44. Chemical classes of hormones
• This chemical classification is useful
functionally because the two classes exert
their effect differently.
• 1. lipid soluble
• 2. water soluble

45. • Lipid soluble • Water soluble
• S T N (station) • A P E (Appe)
• Steroid hormone • Amine hormones
• Thyroid hormones • Peptide hormones
• Nitric oxide gas • Eicosanoid hormones

46. Steroid hormones
• Derived from cholesterol
• Each steroid hormone is unique due to
presence of different chemical groups
attached at various sites on the four rings at
the core of its structure.
• These small differences allow for a large
diversity of function.

48. Two thyroid hormones
• T3 and T4 are synthesized by attaching iodine
to the amino acid tyrosine.
• The benzene ring of tyrosine plus the attached
iodine make T3 and T4 very lipid soluble.

49. Nitric oxide
• It is both, hormone and neurotransmitter.
• Its synthesis is catalyzed by the enzyme nitric
oxide synthesis.

50. Amine hormones
• It is synthesized by decarboxylating and
otherwise modifying certain amino acids.
• They are called amines because they retain an
amino acid group (-NH3+).
• Epinephrine, norepinephrine, dopamine –
synthesized by modifying tyrosine
• Histamine is synthesized by histidine
• Serotonin and melatonin are derived from
tryptophan

51. Histamine
Serotonin

52. Peptide hormones
• They are amino acid polymers
• Smaller peptide hormones consist of chains of
3 to 49 amino acid
• Large protein hormones include 50 to 200
amino acids
• EG: Peptide - anti diuretic hormones, oxytocin
Protein – growth hormone and insulin

53. Human
Insulin

54. Eicosanoid (i-ko-sa-noid) Hormone
• Eicos – twenty and oid – resembling
• They derived from arachidonic acid, a 20-
carbon fatty acid
• EG: Prostaglandins and leukotriene

55. In short,
• Lipid soluble – STN
– Steroid = cholesterol
– T = thyroid
– N = nitric oxide gas
• Water soluble – APE
– Amine group = -NH3+ - histamine, serotonin
– Peptide /Protein = small and large amino acid chain –
oxytocin and GH, Insulin
– Eicosanoid = 20 carbon fatty acid - Prostaglandins

56. Hormone transport
• Most water soluble hormones circulate in the
watery blood plasma in a ‘free’ form (not
attached to any molecules).
• But most lipid soluble hormone are bound to
transport protein.
• The transport protein are synthesis by liver
and have major three functions:

57. 1. They make lipid soluble hormones
temporarily water soluble, thus increasing
their solubility in blood
2. They retard passage of small hormone
molecule through the filtering mechanism in
the kidneys, thus slowing the rate of
hormone loss in urine
3. They provide a ready reserve of
hormone, already present in blood streame.

58. • 0.1 to 10% molecules of lipid soluble hormone
are not bound to transport protein. This free
fraction diffuses our of capillaries, binds to
receptors and triggers responses.
• As free hormone molecules leave the blood
and bind the receptors, transport protein
release new one to replenish the free fraction.

59. Check point
• What is difference between down regulation
and up regulation?
• Identify the chemical classes of hormones and
give an example of each.
• How are hormones transported in the blood?

60. Mechanism of hormone action
Two mechanism of hormone action

61. • Response to a hormone depends on both the
hormone and the target cell.
• Various target cells respond differently to the
same hormone.
• Insulin, stimulates synthesis of glycogen in
liver cells and synthesis of triglyceride in
adipose cells.

62. • The response of hormone is not always the
synthesis of new molecules.
• Other effects like,
• Changing permeability of plasma membrane
• Stimulating transport of a substance into or
out of target cells
• Alerting the rate of specific metabolic
activities
• Causing contraction of smooth muscle or
cardiac muscles

63. • These varied effects are possible because a
single hormone can set in motion several
different cellular responses.
• Hormone must announce its arrival to a
target cell by binding to its receptors.
• The receptors of lipid soluble hormones are
located inside target cells.
• The receptors of water soluble hormones are
part of plasma membrane of target cells.

64. Action of lipid soluble hormones

65. 1. Free lipid soluble
hormone molecules
diffuse through
interstitial fluid,
and through lipid
bilayer of plasma
membrane into
cell.

66. 2. If the cell is target
cell, the hormone
binds with receptors
within cytosol or
nucleus.
The activated
receptor-hormone
complex then alters
gene expression: it
turns specific genes
of the nuclear DNA
on or off.

67. 3. As the DNA
transcribed, new
messenger
RNA, mRNA
forms, leaves the
nucleus, and enters
cytosol.
It directs synthesis
of new
protein, often an
enzyme, on the
ribosomes.

68. 4. The new proteins
alter the cell’s
activity and cause
the responses
typical of that
hormone.

70. Action of water soluble hormones

71. 1. A water soluble
hormone diffuses from
blood through
interstitial fluid and
then binds to its
receptors.
The hormone receptor
complex activates
membrane protein
called a G Protein. This
G protein activates
adenylate cyclase.

72. 2 adenylate cyclase
converts ATP into cyclic
AMP. Because the
enzyme’s active site is
on the inner surface of
the plasma membrane,
this reaction occurs in
the cytosol of the cell.

75. 3 cyclic AMP, the second
messenger, activate one
or more protein
kinases, which may be
free in the cytosol or
bound to plasma
membrane.
A protein kinase is an
enzyme that
phosphorylates other
cellular proteins. The
donor of phosphate group
is ATP which is now

76. 4 active protein kinase
phosphorylate one of
more cellular proteins.
Phosphorylation
activates some of
these protein and
inactivates
others, rather like
turning switch off or
on.

77. 5 Phosphorylated protein in turn
cause reactions that produce
physiological responses. Different
protein kinases exist within
different target cells and within
different organelles of the same
target cell.
Thus one protein might trigger
glycogen synthesis, a second might
cause the break down of
triglyceride, a third may promote
protein synthesis, and so forth.

78. As noted in
4, phosphorylation by a
protein kinase can also
inhibit certain proteins.
For example, some of
the kinases unleashed
when epinephrine
binds to liver cells
inactive an enzyme
needed for glycogen
synthesis.

79. • 6 After a brief
period, an enzyme
called
phosphodiesterase
inactivates cAMP.
Thus, the cells
response is turned off
unless new hormone
molecules continue to
bind to their receptors
in the plasma

80. Free lipid soluble hormone Water soluble hormone molecule
molecule itself as first messenger
On exterior surface of plasma mem.
Activated receptor-hormone  hormone receptor complex
complex
Activation of G Protein and
Adenylate cyclase
New DNA transcribed
(mRNA)
Activation of protein kinase 
phosphorylation
New protein
Various hormonal actions
Final Hormonal response Inactivation of cAMP

81. • Besides cAMP, other second messengers are
calcium ions Ca+2, cGMP (cyclic guanosine
monophosphate), inositol trisphosphate (IP3)
and diacyglycerol (DAG).
• A given hormone may use different second
messengers in different target cells.

82. • Hormones that binds to plasma membrane
receptors can induce their effects at very low
concentration because they initiate a cascade
or chain reaction, each stop of which
multiplies of amplifies the initial effect.
• EG: the binding of a single molecule of
epinephrine to its receptor on a liver cell may
activate a hundred or so G proteins, each of
which activates an adenylate cyclase
molecule.

83. • If each adenylate cyclase produces even 1000
cAMp then 1,00,000 of these second
messengers will be liberated inside the cell.
• Each cAMP may activate a protein
kinase, which in turn can act on hundreds or
thousands of substrate molecules.

87. Second messenger system
• Hormone receptor complex
• G protein
• 1. adenylyl cyclase – cAMP system
• 2. Gaunyl cyclase – cGMP system
• 3. Membrane phopholipase – phospholipid
system IP3
• 4. calcium – calmodulin system

88. Classification (Khurana)
Amines
Proteins,
Chemical
peptides
hormones
Steroids
A - cAMP
Group 1
Mechanism B - cGMP
Group 2
C – Ca or IP3
D – Tyrosine
kinase

89. Ca/Insola Tyrosine
cAMP cGMP
te kinase
Triphosp
Growth
ACTH NO hate hormone
ADH Oxytocin Insulin
Atrial
natriuretic
factor
TSH
Acetilecho
line

90. Action of hormone via tyrosine kinase
• This mechanism of signal generation from the
plasma membrane receptors does not require
G Protein intermediaries.
• These receptors have an extracellular
hormone binding portion, a single trans-
membrane portion and an intra-cytoplasmic
C terminal portion.

91. Hormone receptors Hormone receptors
Posses intrinsic tyrosine Stimulation of intra-
cytoplasmic tyrosine
kinase
auto phosphorylation
Receptor itself becomes phosphorylation
kinase
Enzyme activation & Transcription
transcription

92. Hormonal interactions
Effect on each other

93. The responsive
Influences
ness of a target
by other cell to a hormone
hormones
depends on:
Abundan
ce of
receptors
Concentration
of hormone

94. • A target cell responds more vigorously when
the level of a hormone rises or when it has
more receptors (up regulation).
• In addition, the action of some hormones on
target cells require a simultaneous or recent
exposure to a second hormone.
• In such cases, the second hormone is said to
have A PERMISSIVE EFFECT.

95. • Epinephrine alone only weakly stimulates
lipolysis (the break down of triglycerides).
• But when small amount of thyroid hormones
are present, the same amount of epinephrine
stimulates lipolysis much more powerfully.
• Sometimes the permissive hormone increases
the number of receptor for the other
hormone, and sometime it promotes the
synthesis of an enzyme required for the
expression of other hormone's effect.

96. • When the effect of two hormones acting
together is greater or more extensive than
effect of each hormone acting alone, the two
hormones are said to have SYNERGISTIC
effect.
• EG: normal development of oocytes in the
ovaries requires both FSH from pituitary and
estrogen from ovaries.

97. • When one hormone opposes the action of
another hormone, the two hormones are said
to have ANTAGONISTIC Effects.
• EG: Insulin, which promotes synthesis of
glycogen by liver, and glucagon, which
stimulates breakdown of glycogen in the liver.

98. Checkpoint
• Which factors determine the responsiveness
of target cell to hormone?
• What are differences among permissive
effects, synergistic effects and antagonistic
effects of hormones?

99. Concentration & Life span

100. Concentration
• Hormones are usually secreted in extreme low
concentration
– Peptide – 10 -12 to 10 -10 mol/L
– Epinephrine – 2 × 10 -10

101. Half life
Half life (The term refers to any period of time in which a
quantity falls by half)
Protein hormones Amines Steroids
ADH < 1 min Epinephrine 10s Aldosterone 30m
Norepinephri
Oxytocin < 1 min 15s Cortisol 90m
ne
1,25dihyroxyc
GH <30 min Thyroxin 5-7d 15 h
holecalciferol
Triiodothyron 25hydroxycho
ACTH 15– 25 s 1-3d 15 d
ine lecalciferol

102. Control of hormone secretion
Mechanisms of control of hormone
secretion

103. • The release of most of the hormones occurs in
short bursts, with little or no secretion
between bursts.
• When stimulated, an endocrine gland will
release its hormone in more frequent bursts,
increasing the concentration of hormone in
the blood.
• In absence of stimulation, the blood level of
hormone decreases.

104. Hormone secretion is regulated by
Chemical
changes in
blood
Signals Other
from CNS hormones
Hormone
secretion

106. Feedback Neural Chronotropic
Diural
positive Adrenergic
variations
Menstrual
Negative Cholinergic
rhythm
Seasonal
Dopaminergic
rhythm
Developmental
Serotoninergic
rhythm
GABAergic

109. Positive feedback mechanism

110. Negative feedback mechanism

111. • If the response reverse the stimulus, a system
is operating by negative feedback
• If the response enhances or intensified the
stimulus, a system is operating by positive
feedback

112. Check point
• What three types of signals controls the
hormonal secretion?

113. Measurement of hormones

114. Bioassay
• Injecting the unknown sample of plasma in
experimental animals
• Assessing the Quantitative biological effects
• Quantitative bioassays involve estimation of
the concentration or potency of a substance
by measurement of the biological response
that it produces. Quantitative bioassays are
typically analyzed using the methods of
biostatistics.

115. Immunoassay
• Radioimmunoassy (RIA)
• Enzyme-linked immunosorbent assay
• Studies of antibodies to antigen.

116. Cytochemical assay
• Test is much more sensitive then
immunoassay.
• Cumbersome and time consuming
• Very useful in measuring minute basal levels
of hormone secretions.

117. Dynamic tests
• Not as usual normal condition.
• Two types
• Suppression type – e.g. to know whether a
lung cancer is secreting ACTH
• Stimulating type – corticotrophs of the
pituitary are normally functioning or not.