The Endocrine System
Chapter 46
Types of Chemical Messengers
A hormone is a chemical that is secreted into
extracellular fluid and carried by the blood
-Can therefore act at a distance from source
-Only targets with receptor can respond
Paracrine regulators do not travel in blood
-Allow cells of organ to regulate each other
Pheromones are chemicals released into the
environment to communicate among
individuals of a single species
2
Types of Chemical Messengers
Some neurotransmitters are distributed by the
blood and act as neurohormones
-Norepinephrine coordinates the activity of
heart, liver and blood vessels during stress
Hormone production and release is often
regulated directly or indirectly by the
nervous system
3
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Hormones
carried by blood
Neurotransmitters
Axon
Glands
Target cell
Extracellular
space
Receptor
proteins
Paracrine secretion
4
Endocrine System
The endocrine system includes all the
organs and tissues that produce hormones
-Includes endocrine glands, which are
specialized to secrete hormones
-Also organs, like the liver, that secrete
hormones in addition to other functions
Exocrine glands secrete their products, such
as saliva or milk, into a duct for transport to
the outside
5
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Hypothalamus
Pineal gland
Neurohypophysis
Adenohypophysis
Pituitary
gland
Thyroid gland
Parathyroid glands
(behind thyroid)
Thymus
Adrenal
glands
Pancreas
Testes
(in males)
Ovaries (in females)
6
Classes of Hormones
Molecules that function as hormones must
exhibit two basic characteristics
1. Must be sufficiently complex to convey
regulatory information to their target cells
2. Must be adequately stable to resist
destruction before reaching their target cells
Three chemical classes meet these
requirements
7
Classes of Hormones
1. Peptides and proteins
-Glycoproteins
2. Amino acid derivatives
-Catecholamines
-Thyroid hormones
-Melatonin
3. Steroids
-Sex steroids
-Corticosteroids
8
Classes of Hormones
Hormones may be categorized as:
-Lipophilic (nonpolar) = fat-soluble
-Steroid hormones and thyroid hormones
-Bind to intracellular receptors
-Hydrophilic (polar) = water-soluble
-All other hormones
-Bind to extracellular receptors
9
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Hydrophilic
1. Hormones
Lipophilic
Transport proteins
Secretory
vesicles
Hormones
Hormones
1
secreted into
extracellular
fluid and
diffuse into
1
Blood
vessels
2. Hormones
distributed by
blood to all cells.
Diffuse from blood
to extracellular
fluid.
Endocrine gland A
Endocrine gland B
3. Nontarget
2
Extracellular
fluid
Extracellular
fluid
Nontarget
cells
Nontarget
cells
3
3
4. Target cells
possess
receptors, and are
activated by
hormones.
Membrane
receptors
Activated
cells lack
receptors,
and cell
stimulation does
not occur.
4
4
Activated
Target cell Nuclear
receptor
Target cell
5
5. Unused,
deactivated
hormones are
removed by the
liver and kidney.
10
Paracrine Regulators
Paracrine regulation occurs in most organs
-Growth factors are proteins that promote
growth and cell division in specific organs
-Epidermal growth factor = Skin
-Nerve growth factor = Neurons
-Insulin-like growth factor = Bone
-Cytokines = Immune system
11
Paracrine Regulators
The endothelium of blood vessels is a rich
source of paracrine regulators
-Nitric oxide (NO) which promotes
vasodilation
-Endothelin which stimulates
vasoconstriction
-Bradykinin which promotes vasodilation
12
Paracrine Regulators
Prostaglandins
-A diverse group of fatty acids that are
produced in almost every organ
-Regulate a variety of functions including:
-Smooth muscle contraction, lung
function, labor, and inflammation
-Synthesis is inhibited by nonsteroidal
anti-inflammatory drugs (NSAIDs) such
as aspirin and ibuprofen
13
Lipophilic Hormones
Lipophilic hormones include the steroid
hormones (derived from cholesterol) and
the thyroid hormones (tyrosine + iodine)
-As well as the retinoids, or vitamin A
Testosterone
Cortisol (Hydrocortisone)
CH2OH
HO
H3C
C O
H3C
OH
H3C
H3C
Thyroxine
OH
I
HO
COOH
CH2 CH
O
I
O
I
I
NH2
O
14
Lipophilic Hormones
These hormones circulate in the blood bound
to transport proteins
-Dissociate from carrier at target cells
-Pass through the cell membrane and
bind to an intracellular receptor, either in
the cytoplasm or the nucleus
-Hormone-receptor complex binds to
hormone response elements in DNA
-Regulate gene expression
15
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1. Hormone passes
Blood
plasma
through plasma
membrane
Lipophilic hormones
Plasma membrane
Cytoplasm
Nucleus
2. Inside target
Receptor
cell the hormone
binds to a
receptor protein
in the cytoplasm
or nucleus
3. Hormone-receptor
complex binds to
hormone response
element on DNA,
regulating gene
transcription
5. Change in protein
synthesis is
cellular response
mRNA
Protein
DNA
4. Protein synthesis
Hormone response element
16
Hydrophilic Hormones
Hydrophilic hormones include the peptide,
protein and catecholamine hormones
-Too large or polar to cross cell membrane
Hormones bind to extracellular receptors
-Initiate signal transduction pathways
1. Activation of protein kinases
2. Production of second messengers
17
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1. Receptors Function as Kinase Enzymes
2. Receptors Activate G Proteins
Hormones
Hormone
GPCR
Second messengergenerating enzyme
GPCR
Receptor
b g
GDP a
GTP
Inactive G
protein
Inactive
GTP
Active G
protein
Second
messenger
Active kinase
domain
ATP
Target
protein
ADP
Phosphorylated
protein
Cellular
response
Active
Protein
kinase
Inactive
protein kinase
Target
proteins
Cellular
response
18
Hydrophilic Hormones
Receptor kinases
-For some peptide hormones (like insulin)
the receptor itself is a kinase
-Can directly phosphorylate intracellular
proteins that alter cellular activity
-For other peptide hormones (like growth
hormone) the receptor itself is not a kinase
-Rather, it activates intracellular kinases
19
Hydrophilic Hormones
Second-messenger systems
-Many hydrophilic hormones work through
second messenger systems
-Two have been described:
-One involving cyclic adenosine
monophosphate (cAMP)
-One that generates 2 lipid messengers:
inositol triphosphate (IP3) and diacyl
glycerol (DAG)
20
Hydrophilic Hormones
Second-messenger systems
-Receptors are linked to a secondmessenger-generating enzyme via
membrane proteins called G proteins
-Are thus called G-protein-coupled
receptors (GPCP)
-When the G protein activates the enzyme,
the second-messenger molecules increase
21
The Pituitary Gland
The pituitary gland is also known as the
hypophysis
-It hangs by a stalk from the hypothalamus
The pituitary gland consists of two parts:
-Anterior pituitary (adenohypophysis)
-Appears glandular
-Posterior pituitary (neurohypophysis)
-Appears fibrous
22
The Posterior Pituitary
The posterior pituitary develops from growth
of the brain
-It remains directly connected to the
hypothalamus by a tract of axons
It stores and releases two hormones, that are
actually produced by neuron cell bodies in
the hypothalamus
-Neuroendocrine reflex
23
The Posterior Pituitary
Antidiuretic hormone (ADH)
-A peptide hormone that stimulates water
reabsorption by the kidney, and thus inhibits
diuresis (urine production)
Oxytocin
-Like ADH, it is composed of 9 amino acids
-In mammals, it stimulates the milk ejection
reflex and uterine contractions during labor,
and it regulates reproductive behavior
24
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Stimulus
Stimulus
Stimulus
Osmotic
concentration of
blood increases
Dehydration
Lowers blood
volume and
pressure
Sensor
Sensor
Baroreceptors
in aorta
monitor pressure
Osmoreceptors
in CNS monitor
concentration
(–)
Negative
feedback
Response
Water returned to
blood
Effector
• ADH reduces
urine volume
(–)
Integrating Center
ADH synthesized
by neurosecretory
cells in the
hypothalamus
is released
from neurohypophysis into
blood
Negative
feedback
Response
Increases
blood pressure
Effector
• ADH increases
vasoconstriction
25
The Anterior Pituitary
The anterior pituitary develops from a pouch
of epithelial tissue of the embryo’s mouth
It produces at least seven essential hormones
-Collectively called tropic hormones or
tropins
-Can be categorized into three families
-Peptide hormones, protein hormones
and glycoprotein hormones
26
The Anterior Pituitary
Peptide hormones
-Fewer than 40 amino acids in size
-Adrenocorticotropic hormone (ACTH)
-Melanocyte-stimulating hormone (MSH)
Protein hormones
-A single chain of about 200 amino acid
-Growth hormone (GH)
-Prolactin (PRL)
27
The Anterior Pituitary
Glycoprotein hormones
-Dimers, containing alpha (a) and beta (b)
subunits, each around 100 amino acids
-Thyroid-stimulating hormone (TSH)
-Luteinizing hormone (LH)
-Follicle-stimulating hormone (FSH)
28
The Anterior Pituitary
The activity of the anterior pituitary is
controlled by hormones of the hypothalamus
-Neurons secrete releasing hormones and
inhibiting hormones, which diffuse into
blood capillaries at the hypothalamus’ base
-Each hormone delivered by the
hypothalamohypophysial portal system
regulates a specific anterior pituitary
hormone
29
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Hypothalamus
Neuron cell
bodies
Axons to primary
capillaries
Primary capillaries
Portal veins
Adenohypophysis
Secondary capillaries
Neurohypophysis
Axons to primary
capillaries
Hormones
Primary
capillaries
Portal veins
30
The Anterior Pituitary
The hypothalamus and the anterior pituitary
are partially controlled by the very hormones
whose secretion they stimulate
-This is termed negative feedback or
feedback inhibition
Positive feedback is uncommon because it
causes deviations from homeostasis
-One example is the control of ovulation
31
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(–)
Hypothalamus
Releasing hormones
(TRH, CRH, GnRH)
(+)
Adenohypophysis
(–)
Tropic hormones
(TSH, ACTH, FSH, LH)
(+)
Target Glands
Thyroid, adrenal
cortex, gonads
Target ( + )
cells
Hormones
Negative
feedback
32
The Anterior Pituitary
The anterior pituitary is sometimes referred to
as the “master gland”
-Its effects may be direct or indirect
-Direct: activation of nonendocrine targets
-Indirect: activation of other endocrine
glands
Hypophysectomy is the surgical removal of
the pituitary
33
Anterior Pituitary Disorders
Growth hormone stimulates growth of
muscles and connective tissue
-It also promotes the production of insulinlike growth factors
-Stimulate cell division in the epiphyseal
growth plates, and thus bone elongation
Gigantism is caused by an excessive
secretion of growth hormone in a child
34
Anterior Pituitary Disorders
35
Anterior Pituitary Disorders
In contrast, pituitary dwarfism is caused by a
deficiency in GH secretion during childhood
GH can no longer cause an increase in height
in adults because human skeletal plates
transform from cartilage into bone at puberty
-Excessive GH secretion in an adult results
in acromegaly
36
The Thyroid Gland
In humans, the thyroid gland is shaped like a
bow tie, and lies just below the Adam’s
apple in the front of the neck
-It secretes:
-Thyroid hormones
-Thyroxine
-Triiodothyronine
-Calcitonin
37
The Thyroid Gland
Thyroid hormones bind to nuclear receptors
-Regulate carbohydrate & lipid metabolism
-Adults with hypothyroidism have low
production of thyroxine
-Reduced metabolism and overweight
-Adults with hyperthyroidism have high
production of thyroxine
-High metabolism and weight loss
38
-Trigger metamorphosis in amphibians
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Thyroxine production
Premetamorphosis
Hypothalamus
stimulates
adenohypophysis to
secrete TSH.
–35
–30
–25
Prometamorphosis
Climax
TSH stimulates thyroid to produce
thyroxine.
Forelimbs emerge.
Tail is reabsorbed
.
–20
–15
–10
–5
0
+5
+10
+20
Days from emergence of forelimb
Hypothalamus stimulation
Receptor stimulation
Rapid growth
Reduced growth,
rapid differentiation
Rapid differentiation
39
The Thyroid Gland
Calcitonin
-A peptide hormone
-Stimulates the uptake of calcium (Ca2+)
into bones
-Thus, lowering its levels in the blood
40
The Parathyroid Glands
The parathyroid glands are four small
glands attached to the thyroid
-Produce parathyroid hormone (PTH) in
response to falling levels of Ca2+ in blood
-Stimulates osteoclasts to dissolve
calcium phosphate crystals in the bone
matrix and release Ca2+ into blood
-Stimulates the kidneys to reabsorb Ca2+
from the urine
41
The Parathyroid Glands
PTH also indirectly leads to the absorption of
Ca2+ from food in the intestines by its
activation of vitamin D
-Vitamin D is produced in the skin from a
cholesterol derivative in response to UV light
-It diffuses into blood in an inactive form
-Activated by an enzyme that is
stimulated by PTH
42
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Stimulus
Low blood Ca2+
Parathyroid glands
(–)
Parathyroid
Negative feedback
Secretes
PTH
(+)
Effector
(+)
Effector
(+)
Effector
Increased
Osteoclasts
absorption of Ca2+ Reabsorption of
2+, excretion
Ca
dissolve
Ca(PO4)2
from intestine (due
3–
of PO4
crystals in bone,
to PTH activation
releasing Ca2+
of vitamin D)
Response
Increased
blood Ca2+
43
The Adrenal Glands
The adrenal glands are located just above
each kidney
-Medulla = Inner portion
-Stimulated by the sympathetic division
of the autonomous nervous system
-Cortex = Outer portion
-Stimulated by the anterior pituitary,
through the hormone ACTH
44
The Adrenal Glands
The medulla secretes the catecholamines
epinephrine and norepinephrine
-These trigger “alarm” responses helping
the body prepare for extreme efforts
-Lead to an increase in: heart rate,
blood pressure, blood glucose level, and
blood flow to heart and muscle
45
The Adrenal Glands
The cortex secretes steroid hormones called
corticosteroids
-Glucocorticoids (such as cortisol)
maintain glucose homeostasis and modulate
some aspects of the immune response
-Mineralocorticoids (such as aldosterone)
regulate mineral balance by stimulating the
kidneys to reabsorb Na+ and excrete K+
46
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Stimulus
Stress
Adenohypophysis
(–)
Sympathetic nervous
system
Sympathetic
axons
ACTH secreted from
the adenohypophysis
Negative
feedback
(+)
Adrenal cortex
Effector
Glucocorticoids
Adrenal medulla
Effector
Catecholamine Hormones
• Longer term stress
• Short term stress
response.
response.
• Effects on lipid and
• Effects on cardiovascular
carbohydrate metabolsystem, carbohydrate and
ism, immune system,
lipid metabolism, central
and damage repair.
nervous system.
47
The Pancreas
The pancreas is located adjacent to stomach
-Connected to the duodenum of the small
intestine by the pancreatic duct
The islets of Langerhans are scattered
clusters of cells throughout the pancreas
-These govern blood glucose levels through
two hormones with antagonistic functions
48
The Pancreas
Insulin
-Secreted by beta (b) cells of the islets
-Stimulates cellular uptake of blood glucose
and its storage as glycogen in the liver and
muscle cells or as fat in fat cells
Glucagon
-Secreted by alpha (a) cells of the islets
-Promotes the hydrolysis of glycogen in the
liver and fat in adipose tissue
49
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(–)
Stimulus
After a Meal
Stimulus
Between Meals
Blood glucose increased
Blood glucose decreased
(+)
(–)
(+)
Sensor
Effector
Effector
Increased insulin
production
by b cells
Increased glucagon
production
by a cells
Response
Response
Glucose moves from
blood into cells,
reducing blood glucose
Glycogen hydrolyzed to
glucose, then secreted into
blood, increasing blood glucose
Negative Feedback
Negative Feedback
Pancreatic
Islets
50
Diabetes Mellitus
Diabetics cannot take up glucose from blood
-Type I (insulin-dependent diabetes)
-Individuals lack insulin-secreting b cells
-Treated by daily injections of insulin
-Type II (noninsulin-dependent diabetes)
-Most patients have this form
-Very low number of insulin receptors
-Treated by diet and exercise
51
The Gonads
The ovaries and testes in vertebrates
-Produce sex steroids that regulate
reproductive development
-Estrogen and progesterone
-“Female” hormones
-Androgens
-“Male” hormones
-Testosterone and its derivatives
52
The Pineal Gland
The pineal gland is located in the roof of the
third ventricle of the brain
-Functions as an endocrine gland by
secreting the hormone melatonin
-Reduces dispersal of melanin granules
-Regulates biological clocks
-Synchronizes various body
processes to a circadian rhythm
53
Other Hormones
Some hormones are secreted by organs that
are not exclusively endocrine glands
-Atrial natriuretic hormone is secreted by
the right atrium of the heart
-Promotes salt and water excretion
-Erythropoietin is secreted by the kidney
-Stimulates the bone marrow to produce
red blood cells
54
Insect Hormones
Insects undergo two types of transformations
during post-embryonic development
-Molting = Shedding of old
exoskeleton and secretion of
a new larger one
-Metamorphosis = Radical
transformation from the larval
to the adult form
55
Insect Hormones
Hormonal secretions influence both molting
and metamorphosis
-Brain hormone stimulates prothoracic gland
to produce ecdysone, or molting hormone
-High levels cause molting
-The corpora allata produce a hormone
called the juvenile hormone
-Low levels result in metamorphosis
56
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Neurosecretory cells
Corpora allata
Brain hormone
Juvenile hormone
Prothoracic
gland
Low
amounts
Ecdysone
Larval molt
Pupal molt
Adult molt
57