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Chapter 16:
The Endocrine System
The Endocrine System
• Endocrinology
– Study of hormones and endocrine organs
• Acts with nervous system to coordinate
and integrate activity of body cells
• Influences metabolic activities via
hormones transported via bloodstream
Two Types of Glands
• Exocrine glands
– Non-hormonal secretions (sweat, saliva)
– Have ducts to carry secretion to membrane
surface
• Endocrine glands
– Produce hormones
– Lack ducts (ductless)
Endocrine Glands
•
•
•
•
•
•
•
Pituitary
Thyroid
Parathyroid
Adrenal
Pineal glands
Pancreas
Gonads
Figure 16.1 Location of selected endocrine organs of the body.
Pineal gland
Hypothalamus
Pituitary gland
Thyroid gland
Parathyroid glands
(on dorsal aspect
of thyroid gland)
Thymus
Adrenal glands
Pancreas
Gonads
• Ovary (female)
• Testis (male)
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The Messengers of the Endocrine
System
• Hormones – long-distance chemical
signals that travel in blood or lymph
• Two main classes
– Amino acid-based hormones
• Amino acid derivatives, peptides, and proteins
– Steroids
• Synthesized from cholesterol
Mechanism of Action
• Hormones alter target cell activity via
Cellular Receptor
– Alter plasma membrane permeability
– membrane potential
– Transcriptional activity of enzymes or other
proteins
– Activate or deactivate enzymes
– Induce secretory pathway
– Stimulate cell division
Receptors Transmit Signals via
Secondary Chemical Messengers
Protein Hormone:
• cAMP signaling mechanism
• PIP2-calcium signaling mechanism
– Phosphatidylinositol 4,5-bisphosphate
Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones.
Slide 6
Recall from Chapter 3 that
G protein signaling mechanisms
are like a molecular relay race.
Hormone Receptor G protein Enzyme
2nd
(1st messenger)
messenger
1 Hormone (1st messenger) binds
receptor.
Extracellular fluid
Adenylate cyclase
G protein (Gs)
Receptor
5 cAMP activates
protein kinases.
cAMP
GTP
GTP
ATP
GDP
Inactive
protein
kinase
GTP
Active
protein
kinase
Triggers responses of
target cell (activates
enzymes, stimulates
cellular secretion,
opens ion channel, etc.)
Cytoplasm
2 Receptor
activates G
protein (Gs).
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3 G protein
activates
adenylate
cyclase.
4 Adenylate
cyclase converts
ATP to cAMP (2nd
messenger).
PIP2-calcium signaling mechanism
• Involves G protein and membrane-bound
protein – phospholipase C (PLC)
• Phospholipase C splits PIP2 into two
second messengers – diacylglycerol
(DAG) and inositol trisphosphate (IP3)
• DAG activates PKC; IP3 causes Ca2+ release
• Calcium ions act like a second messenger to
continue the signal
PIP2
IP3
Steroid Hormones
1. Diffuse into target cells and bind with
intracellular receptors
2. Receptor-hormone complex enters nucleus;
binds to specific region of DNA
3. Prompts DNA transcription to produce
mRNA, promoting protein synthesis
Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones.
Extracellular
fluid
Steroid
hormone
Plasma
membrane
Cytoplasm
Receptor
protein
Nucleus
Slide 6
1 The steroid hormone diffuses
through the plasma membrane
and binds an intracellular
receptor.
Receptorhormone
complex
2 The receptorhormone complex enters the
nucleus.
Receptor
Binding region
DNA
3 The receptor- hormone
complex binds a specific DNA
region.
4
Binding initiates transcription
of the gene to mRNA.
mRNA
5 The mRNA directs protein
synthesis.
New protein
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3 Stimuli Events for Endocrine
Secretion
• Endocrine gland stimulated to synthesize
and release hormones in response to
– Humoral stimuli
– Neural stimuli
– Hormonal stimuli
Humoral Stimuli
• Changing blood levels of ions and
nutrients directly stimulate secretion of
hormones
Neural Stimuli
• Nerve fibers stimulate hormone release
Hormonal Stimuli
• Hormones stimulate other endocrine
organs to release their hormones
The Pituitary Gland and Hypothalamus
• Pituitary gland (hypophysis) has two
major lobes
– Posterior (lobe)
• Neural tissue
– Anterior (lobe) (adenohypophysis)
• Glandular tissue
The Hypothalamus
• Hypothalamus is neuroendocrine organ
• Produces and secretes hormones
• Regulates and can be regulated by other
endocrine organs
The Posterior Lobe and Hypothalamus
• Downgrowth of hypothalamic neural tissue
• Neural connection to hypothalamus
(hypothalamic-hypophyseal tract)
• Hypothalamus synthesize neurohormones
oxytocin and antidiuretic hormone
(ADH)
– transported to and stored in posterior pituitary
Figure 16.5a The hypothalamus controls release of hormones from the pituitary
Slide 5
gland in two different ways (1 of 2).
Paraventricular nucleus
Hypothalamus
Posterior lobe
of pituitary
Optic
chiasma
Infundibulum
(connecting stalk)
Hypothalamichypophyseal
tract
Supraoptic
nucleus
Inferior
hypophyseal
artery
Axon terminals
2 Oxytocin and ADH are
transported down the axons of the
hypothalamic- hypophyseal tract to
the posterior pituitary.
3 Oxytocin and ADH are
stored in axon terminals in the
posterior pituitary.
Posterior lobe
of pituitary
Oxytocin
ADH
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1 Hypothalamic neurons
synthesize oxytocin or
antidiuretic hormone (ADH).
4
When hypothalamic neurons fire,
action potentials arriving at the
axon terminals cause oxytocin or
ADH to be released into the blood.
The Anterior Lobe of Pituitary
• Vascular connection to hypothalamus
– Hypophyseal portal system
• Transport of releasing and inhibiting hormones
created by the hypothalamus to the anterior
pituitary to regulate additional hormone secretion
Figure 16.5b The hypothalamus controls release of hormones from the pituitary
Slide 4
gland in two different ways (2 of 2).
Hypothalamus
Anterior lobe
of pituitary
Superior
hypophyseal
artery
2 Hypothalamic hormones travel
through portal veins to the anterior
pituitary where
they stimulate or inhibit
release of hormones made in the
anterior pituitary.
3 In response to releasing
hormones, the anterior pituitary
secretes hormones into the
secondary capillary plexus. This
in turn empties into the general
circulation.
GH, TSH, ACTH,
FSH, LH, PRL
Anterior lobe
of pituitary
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Hypothalamic
neurons synthesize
GHRH, GHIH, TRH,
CRH, GnRH, PIH.
1 When appropriately stimulated,
hypothalamic neurons secrete
releasing or inhibiting hormones into
the primary capillary plexus.
Hypophyseal
portal system
• Primary capillary
plexus
• Hypophyseal
portal veins
• Secondary
capillary plexus
A portal
system is
two
capillary
plexuses
(beds)
connected
by veins.
Hormones of Anterior Pituitary
• Oxytocin and ADH (Antidiuretic
Hormone)
– peptide hormones
Oxytocin
• Strong stimulant of uterine contraction
• Hormonal trigger for milk ejection
• Acts as neurotransmitter in brain
– sexual and affectionate behavior
• “cuddle” hormone
Antidiuretic Hormone (ADH)
• Inhibits or prevents urine formation via
regulating water balance
• Hypothalamic neurons monitor solute
concentration
– Solute concentration too high (low water)
• kidneys reabsorb more water
ADH Regulation
• Less water in urine, low urine output
– more water in bloodstream resulting in lower
solute concentrations
• Feedback loop:
– solute levels low, no ADH
– solute levels high, ADH production
AHD Deficiency
• Diabetes insipidus
– intense thirst and large urine output
– due to hypothalamus or posterior pituitary
damage
• Note: Diseases/disorders caused by
hyposecretion or hypersecretion of hormones
Anterior Pituitary Hormones
• Growth hormone (GH)
• Thyroid-stimulating hormone (TSH) or
thyrotropin
• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Prolactin (PRL)
Anterior Pituitary Hormones
• Protein hormones
• All except GH activate cyclic AMP secondmessenger systems at their targets
• TSH, ACTH, FSH, and LH are all tropic
hormones
– regulate secretory action of other endocrine
glands
GH Regulation
• GH release regulated by hypothalamic
hormones
– Growth hormone–releasing hormone (GHRH)
– Growth hormone–inhibiting hormone (GHIH)
GH Biological Action
• Indirect actions on growth
– via insulin-like growth factors (IGFs) via
IGFRs – bone and muscle growth
• Direct actions on metabolism
– Increases blood levels of fatty acids and
stimulates use of fatty acids for fuel (fat loss)
– Decreases rate of glucose uptake and
metabolism (glucose conservation)
Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH).
Inhibits GHRH release
Stimulates GHIH release
Feedback
Anterior
pituitary
Hypothalamus
secretes growth
hormone–releasing
hormone (GHRH), and
GHIH (somatostatin)
Inhibits GH synthesis
and release
Growth hormone (GH)
Indirect actions
Direct actions
(growthpromoting)
(metabolic,
anti-insulin)
Liver and
other tissues
Produce
Insulin-like growth
factors (IGFs)
Effects
Effects
Skeletal
Extraskeletal
Fat
metabolism
Carbohydrate
metabolism
Increases, stimulates
Reduces, inhibits
Increased cartilage
formation and
skeletal growth
Increased protein
synthesis, and
cell growth and
proliferation
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Increased
fat breakdown
and release
Increased blood
glucose and other
anti-insulin effects
Initial stimulus
Physiological response
Result
Feedback inhibition
• Hallmark regulatory mechanism
• Inhibitory effect
– Stimulus created
– Production of signal (hormone)
– Signal acts to stimulate desired outcome
– Signal also acts to shut down stimulus that
created signal to begin with
The Thyroid Gland
• Butterfly-shaped gland located in the front of the neck,
on the trachea, under the larynx
• The largest pure endocrine gland in body
• Composed of hollow follicles formed by follicular cells
• Produces Thyroid Hormone upon stimulation by
Thyroid-stimulating hormone via anterior pituitary
Inside the Thyroid
• Follicular cells produce thyroglobulin
• Follicles
– filled with fluid of thyroglobulin + iodine
• Parathyroid cells produce calcitonin
Figure 16.9 The thyroid gland.
Hyoid bone
Thyroid cartilage
Common carotid
artery
Epiglottis
Colloid-filled
follicles
Follicular cells
Superior thyroid
artery
Inferior thyroid
artery
Isthmus of
thyroid gland
Trachea
Left subclavian
artery
Left lateral
lobe of thyroid
gland
Aorta
Parafollicular cells
Gross anatomy of the thyroid gland, anterior view
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Photomicrograph of thyroid gland
follicles (145x)
Thyroid Hormone (TH)
• Created by the cleavage of a
thyroglobulin-iodine complex created in
the lumen of follicle
• Two iodine-bound amine hormones:
– T4 (thyroxine); has 2 tyrosines + 4 bound
iodine atoms
– T3 (triiodothyronine); has 2 tyrosines + 3
bound iodine atoms
Figure 16.10 Synthesis of thyroid hormone.
Slide 8
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Tyrosines (part of thyroglobulin
molecule)
Capillary
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodine
3 Iodide
is oxidized
to iodine.
2 Iodide (I–) is trapped
(actively transported in).
Iodide (I−)
T4
T3
Lysosome
DIT
MIT
Thyroglobulin
colloid
5 Iodinated tyrosines are
linked together to form T3
and T4.
T4
T3
T4
T3
To peripheral tissues
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6 Thyroglobulin colloid is
endocytosed and combined
with a lysosome.
7 Lysosomal enzymes
cleave T4 and T3 from
thyroglobulin and hormones
diffuse into bloodstream.
Colloid in
lumen of
follicle
Mechanism of T3/T4 synthesis
T3 vs T4
Transport and Regulation of TH
• T4 and T3 transported by thyroxine-binding
globulins (TBGs)
• Both bind to target receptors, but T3 is ten
times more active than T4
• Peripheral tissues convert T4 to T3
TH Action
• Body’s major metabolic hormone
• Effects almost every cell in the body
• Refer to Table 16.2 for major effects
– basal metabolic rate and oxygen use
– metabolism
– growth and development
– normal reproductive ability
Figure 16.8 Regulation of thyroid hormone secretion.
Hypothalamus
TRH Thyrotropin releasing hormone
Anterior pituitary
TSH Thyrotropin stimulating hormone
Thyroid gland
Thyroid
hormones
Target cells
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Stimulates
Inhibits
The Parathyroid Glands
• Tiny, yellow-brown glands in the posterior
aspect of the thyroid gland
• Two major cell types
– oxyphil cells (function unknown)
– parathyroid (chief) cells – secrete
parathyroid hormone (PTH) or
parathormone
Figure 16.12 The parathyroid glands.
Pharynx
(posterior
aspect)
Capillary
Thyroid
gland
Parathyroid
glands
Esophagus
Trachea
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Parathyroid
cells
(secrete
parathyroid
hormone)
Oxyphil
cells
Parathyroid Hormone
• Most important hormone in Ca2+
homeostasis
– Stimulates osteoclasts to digest bone matrix
and release Ca2+ to blood
– Enhances reabsorption of Ca2+ and secretion
of phosphate (PO43-) by kidneys
– Promotes activation of vitamin D (by kidneys)
which is required for absorption of Ca2+ from
food
Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine.
Hypocalcemia
(low blood Ca2+)
PTH release from
parathyroid gland
Osteoclast activity
in bone causes Ca2+
and PO43- release
into blood
Ca2+ reabsorption
in kidney tubule
Activation of
vitamin D by kidney
Ca2+ absorption
from food in small
intestine
Ca2+ in blood
Initial stimulus
Physiological response
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Result
PTH Calcium mechanism of Action
• Ca2+ sensitive receptor (GPCR) binds to
extracellular Ca2+ levels
• Increased Ca2+ activates GPCR
PLC activation via G protein
 intracellular Ca levels
 inhibition of secretory release of PTH (exocytosis)
The Adrenal glands (Suprarenal)
• Paired, pyramid-shaped organs on top of
kidneys
• Structurally and functionally two glands in
one
– Adrenal medulla – composed of nervous
tissue
– Adrenal cortex – encapsulates the medulla,
composed of glandular tissue
Adrenal Cortex
• Composed of three layers that produce
three different corticosteroids
– Zona glomerulosa
• produces mineralocorticoids
– Zona fasciculata
• produces glucocorticoids
– Zona reticularis
• produces gonadocorticoids
Figure 16.14 Microscopic structure of the adrenal gland.
Hormones
secreted
Zona
glomerulosa
Aldosterone
Zona
fasciculata
Cortex
Adrenal gland
• Medulla
• Cortex
Capsule
Cortisol
and
androgens
Kidney
Medulla
Zona
reticularis
Adrenal
medulla
Drawing of the histology of the
adrenal cortex and a portion of
the adrenal medulla
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Epinephrine
and
norepinephrine
Photomicrograph (115x)
Mineralocorticoids (Aldosterone)
• Regulate electrolytes in extracellular fluids
– Na+ affects ECF volume, blood volume, blood
pressure
– where Na+ goes, so does water and other
essential ions
– K+ regulates resting membrane potential of all
cells (RMP), actions potentials in nerve and
muscle.
Stimulation of Aldosterone
• Release triggered by
– Changes in blood volume and blood pressure
– Rising blood levels of K+
– Stress
• Aldosterone stimulates
– reduces excretion of Na+ from body by
stimulating Na+ (water) reabsorption
– elimination of K+
Effect of Aldosterone
• Increased absorption of Na+
• Increased secretion of K+
• Increased Blood pressure/blood volume
The Renin-AngiotensinAldosterone Mechanism
• BP/BV falls – kidneys release renin
• Renin cleaves angiotensinogen (liver)
• Activation of angiotensin II via cleavage.
• Angiotensin II stimulates production of
aldosterone at zona glomerulosa
Increasing BP/BV
• Atrial Natriuretic Peptide (ANP) secreted by
heart
• ANP inhibits renin and aldosterone secretion
• Allows Na+ and water excretion
Blood Concentration of K+
• Increased K+ levels directly stimulates
aldosterone production at zona glomerulosa
• Aldosterone promotes increased K+ excretion
• Conversely, decreased K+ levels inhibits
release of aldosterone
Stress
• Severe stress releases corticotrophin releasing
hormone (CRH) from the hypothalamus
• CRH increases adrenocorticotrophic hormone
(ATCH) from pituitary gland
• ATCH stimulates aldosterone secretion
• Increase in blood volume/pressure
Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex.
Primary regulators
Blood volume
and/or blood
pressure
K+ in blood
Other factors
Stress
Blood pressure
and/or blood
volume
Hypothalamus
Kidney
Heart
CRH
Renin
Direct
stimulating
effect
Initiates
cascade
that
produces
Anterior
pituitary
Atrial natriuretic
peptide (ANP)
ACTH
Angiotensin II
Inhibitory
effect
Zona glomerulosa
of adrenal cortex
Enhanced
secretion
of aldosterone
Targets
kidney tubules
Absorption of Na+ and
water; increased K+ excretion
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Blood volume
and/or blood pressure
Zona fasciculata and
Glucocorticoids
• Steroid hormone
• Influence energy metabolism of most body cells
and help resist stressors
• Help keep blood glucose constant during food
intake
• Maintain blood pressure by increasing action of
vasoconstrictors
Glucocorticoids
• Major hormone is cortisol (hydrocortisone)
• Action via regulating gene transcription
• ACTH activates cortisol release (Pituitary)
• Increasing cortisol inhibits CRH
(hypothalamus)and corresponding ACTH release
Cortisol Action
• Prime metabolic effect is gluconeogenesis formation of glucose from fats and proteins
– Promotes rises in blood glucose, fatty acids, and
amino acids
• Enhances vasoconstriction  rise in blood
pressure to quickly distribute nutrients to cells
Glucocorticoids
• Can control chronic inflammatory disorders
– rheumatoid arthritis
– allergic responses
• Used for cancer therapy due to anti-inflammatory
effects
– combinatorial therapy
• How much is too much, too little?
– Cushing’s syndrome (too much)
– Addison’s disease (too little)
The Adrenal Medulla
• Controlled by nervous system
• Composed of medullary chromaffin cells
that synthesize catecholamines
– epinephrine (adrenaline)
– norepinephrine
The Adrenal Medulla
• The stress response pathway (fight or flight
status)
• Effects
– Vasoconstriction
– Increased heart rate
– Increased blood glucose levels
– Blood diverted to brain, heart, and skeletal
muscle
Figure 16.17 Stress and the adrenal gland.
Short-term stress
Prolonged stress
Stress
Nerve impulses
Hypothalamus
CRH (corticotropinreleasing hormone)
Spinal cord
Corticotropic cells
of anterior pituitary
To target in blood
Preganglionic
sympathetic
fibers
Adrenal medulla
(secretes amino acid–
based hormones)
Catecholamines
(epinephrine and
norepinephrine)
Short-term stress response
• Heart rate increases
• Blood pressure increases
• Bronchioles dilate
• Liver converts glycogen to glucose and releases
glucose to blood
• Blood flow changes, reducing digestive system activity
and urine output
• Metabolic rate increases
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ACTH
Mineralocorticoids
Adrenal cortex
(secretes steroid
hormones)
Glucocorticoids
Long-term stress response
• Kidneys retain
• Proteins and fats converted
sodium and water
to glucose or broken down
for energy
• Blood volume and
• Blood glucose increases
blood pressure
• Immune system
rise
supressed
Short term vs Long term Stress
• Short term
– Action via preganglionic sympathtic fibers to
Adrenal medulla to secrete catecholamines
• Long term
– Action via hypothalamus to anterior pituitary to
Adrenal cortex to secrete mineralocorticoids and
glucocorticoids
Pineal Gland
Tiny, pine cone-shaped
gland that hangs from
the roof of the third
ventricle in the brain
Function still a mystery
Major peptide
hormone is malatonin
The Pineal Gland
• Secretory cells called pinealocytes
– secrete melatonin
• Melatonin may affect
– Timing of sexual maturation and puberty
– Day/night cycles
– Physiological processes that show rhythmic variations
(body temperature, sleep, appetite)
– Production of antioxidant and detoxification molecules
in cells
Pancreas
• Triangular, elongated gland partially behind
stomach
• Has both exocrine and endocrine cells
• Acinar cells form the bulk of the gland
• Scattered throughout are clusters of Pancreatic
islets (islets of Langerhans)
Pancreas Histology
• Acinar Cells (exocrine function)
– secrete enzyme rich juice to small intestines to aid
in digestion
• Pancreatic islets (endocrine function)
• Alpha () cells produce glucagon (hyperglycemic
hormone)
• Beta () cells produce insulin (hypoglycemic hormone)
Figure 16.18 Photomicrograph of differentially stained pancreatic tissue.
Pancreatic islet
•  (Glucagonproducing)
cells
•  (Insulinproducing)
cells
Pancreatic acinar
cells (exocrine)
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Glucagon
• Produced by alpha cells
• Major target—liver
• Causes increased blood glucose levels
– Glycogenolysis—breakdown of glycogen to
glucose
– Gluconeogenesis—synthesis of glucose from lactic
acid and other biomolecules
– Release of glucose to blood
Insulin
• Lowers blood glucose levels
– Enhances membrane transport of glucose into
fat and muscle cells
– Inhibits glycogenolysis and gluconeogenesis
– Participates in neuronal development and
learning and memory
Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels.
Stimulates glucose
uptake by cells
Tissue cells
Insulin
Stimulates
glycogen
formationw
Pancreas
Glucose
Glycogen
Blood
glucose
falls to
normal
range.
Liver
Stimulus
Blood
glucose level
Stimulus
Blood
glucose level
Blood
glucose
rises to
normal
range.
Pancreas
Glucose
Glycogen
Liver
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Stimulates
glycogen
breakdown
Glucagon
Other organs and hormone secretion
•
•
•
•
•
•
•
Gonads (Ch. 27)
Adipose Tissue
GI tract (Ch. 23)
Heart (Chps. 18 and 19)
Kidneys (Ch. 25)
Skeleton
Skin
Today’s Lab
• Lab Exercise 27
– Read Objectives of the exercise
• The introduction of the lab is a repeat of the
lecture but will serve as a useful guide to
completing the assignment