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Chapter 18
The Endocrine System
© 2018 Pearson Education, Inc.
An Introduction to the Endocrine System
Endocrine system
– Endocrine cells and tissues produce about 30 different
hormones (chemical messengers)
– Controls and coordinates body processes
2
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18-1 Intercellular Communication
Mechanisms of intercellular communication
– Direct communication
• Exchange of ions and molecules between adjacent
cells across gap junctions
• Occurs between two cells of the same type
• Highly specialized and relatively rare
– Paracrine communication
• Chemical signals transfer information from cell to
cell within a single tissue
3
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18-1 Intercellular Communication
Mechanisms of intercellular communication
– Autocrine communication
• Messages affect the same cells that secrete them
• Chemicals involved are autocrines
• Example: prostaglandins secreted by smooth
muscle cells cause the same cells to contract
– Endocrine communication
• Endocrine cells release chemicals (hormones) that
are transported in bloodstream
• Alters metabolic activities of many organs
4
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18-1 Intercellular Communication
Target cells
– Have receptors needed to bind and “read” hormonal
messages
Hormones
– Change types, quantities, or activities of enzymes and
structural proteins in target cells
– Can alter metabolic activities of multiple tissues and
organs at the same time
– Affect long-term processes like growth and
development
5
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18-1 Intercellular Communication
Synaptic communication
– Neurons release neurotransmitters at a synapse
– Leads to action potentials that are propagated along
axons
– Allows for high-speed “messages” to reach specific
destinations
– Ideal for crisis management
6
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18-2 Hormones
Both endocrine and nervous systems
– Rely on release of chemicals that bind to specific
receptors on target cells
– Share many chemical messengers (e.g.,
norepinephrine and epinephrine)
– Are regulated mainly by negative feedback
– Function to preserve homeostasis by coordinating and
regulating activities
7
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18-2 Hormones
Endocrine system
– Includes all endocrine cells and tissues that produce
hormones or paracrines
– Endocrine cells release secretions into extracellular
fluid
• Unlike exocrine cells
– Endocrine organs are scattered throughout body
8
Figure 18–1 Organs and Tissues of the Endocrine System (Part 1 of 2).
Hypothalamus
Production of ADH, OXT,
and regulatory hormones
Pituitary Gland
Anterior lobe
ACTH, TSH, GH, PRL,
FSH, LH, and MSH
Posterior lobe
Release of oxytocin (OXT)
and antidiuretic hormone (ADH)
Pineal Gland
Melatonin
Parathyroid Glands
(located on the posterior surfacesof the thyroid gland)
Parathyroid hormone (PTH)
9
Figure 18–1 Organs and Tissues of the Endocrine System (Part 2 of 2).
Organs with Secondary
Endocrine Functions
Heart
• Atrial natriuretic peptide (ANP)
• Brain natriuretic peptide (BNP)
Thymus (undergoes atrophy
during adulthood)
• Thymosins
Adipose Tissue
• Leptin
Digestive Tract
Secretes numerous hormones
involved in the coordination of
system functions, glucose
metabolism, and appetite
Kidneys
• Erythropoietin (EPO)
• Calcitriol
Gonads
Testes (male)
• Androgens (especially testosterone)• Inhibin
Ovary
Ovaries (female)
• Estrogens
• Progesterone
• Inhibin
See
Chapter
25
See
Chapter
21
See
Chapter
22
Thyroid Gland
Thyroxine (T4)
Triiodothyronine (T3)
Calcitonin (CT)
Adrenal Glands
Medulla
Epinephrine (E)
Norepinephrine (NE)
Cortex
Cortisol, corticosterone,
cortisone, aldosterone,
androgens
Pancreas
(Pancreatic Islets)
Insulin, glucagon
KEY TO PITUITARY HORMONES
ACTH
TSH
GH
PRL
FSH
LH
MSH
Adrenocorticotropic hormone
Thyroid-stimulating hormone
Growth hormone
Prolactin
Follicle-stimulating hormone
Luteinizing hormone
Melanocyte-stimulating hormone
Testis
See
Chapters
19 and 26
See
Chapters
28 and 29
10
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18-2 Hormones
Classes of hormones
– Amino acid derivatives
– Peptide hormones
– Lipid derivatives
11
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18-2 Hormones
Amino acid derivatives (biogenic amines)
– Small molecules structurally related to amino acids
– Derivatives of tyrosine
• Thyroid hormones
• Catecholamines (epinephrine, norepinephrine, and
dopamine)
– Derivatives of tryptophan
• Serotonin and melatonin
12
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18-2 Hormones
Peptide hormones
– Chains of amino acids
– Most are synthesized as prohormones
• Inactive molecules converted to active hormones
before or after they are secreted
– Glycoproteins
• Proteins more than 200 amino acids long that have
carbohydrate side chains (e.g., TSH, LH, FSH)
– Short polypeptides/small proteins
13
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18-2 Hormones
Peptide hormones
– Short-chain polypeptides
• ADH and OXT are each 9 amino acids long
– Small proteins
• Insulin (51 amino acids)
• Growth hormone (191 amino acids)
• Prolactin (198 amino acids)
– Includes all hormones secreted by hypothalamus,
heart, thymus, digestive tract, pancreas, posterior lobe
of the pituitary gland, etc.
14
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18-2 Hormones
Lipid derivatives
– Eicosanoids—derived from arachidonic acid, a 20-
carbon fatty acid
• Paracrines that coordinate cellular activities and
affect enzymatic processes (such as blood clotting)
• Some eicosanoids (such as leukotrienes) have
secondary roles as hormones
• Prostaglandins coordinate local cellular activities
– Converted to thromboxanes and prostacyclins in
some tissues
15
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18-2 Hormones
Lipid derivatives
– Steroid hormones—derived from cholesterol
• Include
– Androgens from testes in males
– Estrogens and progesterone from ovaries in
females
– Corticosteroids from adrenal cortex
– Calcitriol from kidneys
• Bound to specific transport proteins in the plasma
– Remain in circulation longer than peptide
hormones
16
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18-2 Hormones
Transport and inactivation of hormones
– Hormones may circulate freely or travel bound to
special carrier proteins
– Free hormones remain functional for less than an hour
and are inactivated when they
• Diffuse out of bloodstream and bind to receptors on
target cells,
• Are absorbed and broken down by liver or kidneys,
or
• Are broken down by enzymes in blood or interstitial
fluids
17
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18-2 Hormones
Transport and inactivation of hormones
– Thyroid and steroid hormones
• Remain functional much longer
• More than 99 percent become attached to special
transport proteins in blood
• Equilibrium state exists between free and bound
forms
• Bloodstream contains a substantial reserve of
bound hormones
18
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18-2 Hormones
Mechanisms of hormone action
– Binding of a hormone may
• Alter genetic activity
• Alter rate of protein synthesis
• Change membrane permeability
19
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18-2 Hormones
Hormone receptor
– A protein molecule to which a particular molecule binds
strongly
– Different tissues have different combinations of
receptors
– Presence or absence of a specific receptor determines
hormonal sensitivity of a cell
20
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18-2 Hormones
Down-regulation
– Presence of a hormone triggers a decrease in the
number of hormone receptors
– When levels of a particular hormone are high, cells
become less sensitive to it
Up-regulation
– Absence of a hormone triggers an increase in the
number of hormone receptors
– When levels of a particular hormone are low, cells
become more sensitive to it
21
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18-2 Hormones
Catecholamines and peptide hormones
– Not lipid soluble
– Unable to penetrate plasma membrane
– Bind to receptor proteins on outer surface of plasma
membrane (extracellular receptors)
Steroid and thyroid hormones
– Lipid soluble
– Diffuse across plasma membrane and bind to
receptors inside cell (intracellular receptors)
22
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18-2 Hormones
Hormones and extracellular receptors
– First messenger
• Hormone that binds to extracellular receptor
• Promotes release of second messenger in cell
– Second messenger
• Intermediary molecule that appears due to
hormone–receptor interaction
• May act as enzyme activator, inhibitor, or cofactor
• Results in change in rates of metabolic reactions
• Example: cAMP, cGMP, Ca2+
23
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18-2 Hormones
Process of amplification
– When a small number of hormone molecules binds to
extracellular receptors,
• Thousands of second messengers may appear
– Magnifies effect of hormone on target cell
24
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18-2 Hormones
G protein
– Enzyme complex coupled to membrane receptor
– Protein binds GTP
– Involved in link between first messenger and second
messenger
25
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18-2 Hormones
G proteins and cAMP
– Steps involved in increasing cAMP level, which
accelerates metabolic activity of cell
1. Activated G protein activates adenylate cyclase
2. Adenylate cyclase converts ATP to cyclic AMP
3. Cyclic AMP functions as a second messenger
4. Generally, cyclic AMP activates kinases that
phosphorylate proteins
– Increase in cAMP level is usually short-lived
• Phosphodiesterase (PDE) converts cAMP to AMP
26
Figure 18–3a G Proteins and Second Messengers.
The first messenger
(a peptide hormone,
catecholamine, or
eicosanoid) binds to a
membrane receptor and
activates a G protein.
Hormone
A G protein is an
enzyme complex
coupled to a
membrane receptor
that serves as a link
between the first and
second messenger.
Hormone
Proteinreceptor
G protein(inactive)
Proteinreceptor
G proteinactivated
a Effects on cAMP Level
Many G proteins, once activated, exert their effects by changing the
concentration of cyclic AMP, which acts as the second messenger within the
cell.
HormoneHormone
Protein
receptor
G proteinactivated
Acts as
second
messenger
adenylate
cyclase
Proteinreceptor
Increased
production
of cAMP
ATP
G proteinactivated
PDE
Enhanced
breakdown
of cAMP
AMPcAMP
kinase
Opens ion
channels
Activates
enzymes
Reduced
enzyme
activity
If levels of cAMP increase,
enzymes may be activated
or ion channels may be
opened, accelerating the
metabolic activity of the cell.
In some instances, G protein
activation results in
decreased levels of cAMP in
the cytoplasm. This decrease
has an inhibitory effect on
the cell.
First Messenger Examples
• Epinephrine and
norepinephrine
First Messenger Examples
• Epinephrine and
norepinephrine
• Calcitonin
• Parathyroid hormone
• ADH, ACTH, FSH, LH, TSH
cAMP
a
27
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18-2 Hormones
G proteins and calcium ions
1. G protein activates phospholipase C (PLC)
2. Triggers receptor cascade beginning with production
of diacylglycerol (DAG) and inositol triphosphate
(IP3) from phospholipids
3. IP3 diffuses into cytoplasm and triggers release of
Ca2+ from intracellular reserves
4. Calcium ion channels open due to activation of
protein kinase C (PKC), and Ca2+ enters cell
5. Ca2+ binds to calmodulin, activating enzymes
28
Figure 18–3b G Proteins and Second Messengers.
The first messenger
(a peptide hormone,
catecholamine, or
eicosanoid) binds to a
membrane receptor and
activates a G protein.
Hormone
A G protein is an
enzyme complex
coupled to a
membrane receptor
that serves as a link
between the first and
second messenger.
Hormone
Proteinreceptor
G protein(inactive)
Proteinreceptor
G proteinactivated
Effects on Ca2+
Level
Hormone
Proteinreceptor
G proteinactivated
PKC
Calmodulin
Activates
enzymes
First Messenger Examples
• Epinephrine and norepinephrine
• Oxytocin
• Regulatory hormones of hypothalamus
• Several eicosanoids
b
29
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18-2 Hormones
Hormones and intracellular receptors
– Steroid hormones can alter rate of DNA transcription in
nucleus
– Alterations in synthesis of enzymes or structural
proteins
• Directly affect activity and structure of target cell
– Thyroid hormones bind to receptors within nucleus and
on mitochondria
• Activate genes or change rate of transcription
• Increase rates of ATP production
30
Figure 18–4a Effects of Intracellular Hormone Binding.
Steroid hormones diffuse through the plasma membrane
and bind to receptors in the cytoplasm or nucleus.
The complex then binds to DNA in the nucleus,
activating specific genes.
1
Diffusion through
membrane lipids
Target cell response
CYTOPLASM
Alteration of cellular
structure or activity
6
Receptor
Binding of hormone
to cytoplasmic or
nuclear receptors
Translation and
protein synthesis
2
5
Transcription and
mRNA production
Receptor
Nuclear
pore
Nuclear
envelope
3
4
Gene activation
Binding of
hormone–receptor
complex to DNA
a
31
Figure 18–4b Effects of Intracellular Hormone Binding.
Thyroid hormones enter the cytoplasm and bind to
receptors in the nucleus to activate specific genes.
They also bind to receptors on mitochondria and
accelerate ATP production.
1
Transport across
plasma membrane
Target cell response
Increased
ATP
production
Receptor6
Translation and
protein synthesis
2
Binding of receptors
at mitochondria and
nucleus
5
Transcription and
mRNA production
Receptor
4Gene activation
3
Binding of
hormone–receptor
complex to DNA
Alteration of cellular
structure or activity
b
32
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18-2 Hormones
Hormone secretion
– Mainly controlled by negative feedback
• Stimulus triggers production of hormone that
reduces intensity of the stimulus
– Can be triggered by
• Humoral stimuli (change in extracellular fluid),
• Hormonal stimuli (arrival or removal of hormone), or
• Neural stimuli (neurotransmitters)
33
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18-2 Hormones
Control of hormone secretion
– May involve only one hormone
– Humoral stimuli
• Control hormone secretion by heart, pancreas,
parathyroid gland, and digestive tract
– Hormonal stimuli
• May involve one or more intermediary steps
• Two or more hormones involved
– Neural stimuli
• Hypothalamus provides highest level of control
34
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18-3 The Pituitary Gland
Pituitary gland (hypophysis)
– Lies within sella turcica
• Sellar diaphragm isolates pituitary gland from
cranial cavity
– Hangs inferior to hypothalamus
• Connected by infundibulum
– Releases nine important peptide hormones
• Bind to extracellular receptors
• Use cAMP as second messenger
35
Figure 18–5a The Orientation and Anatomy of the Pituitary Gland.
Third
ventricle
Hypothalamus
Optic chiasm
Infundibulum
Sellar diaphragm
Anterior Pituitary Lobe
Pars tuberalis
Pars distalis
Pars intermedia
Mammillary
body
Posterior
pituitary
lobe
Sphenoid
(sella turcica)
Relationship of the pituitary
gland to the hypothalamus
a
36
Anterior Pituitary Lobe
Pars
distalis
Pars
intermedia
Posterior
pituitary
lobe
Secretes other
pituitary
hormones
Pituitary gland
Secretes
MSH
Releases
ADH and
OXT
LM × 77
Histology of the pituitary gland showing the
anterior and posterior lobes
b
Figure 18–5b The Orientation and Anatomy of the Pituitary Gland.
37
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18-3 The Pituitary Gland
The hypothalamus
– Regulates functions of the pituitary gland
– Synthesizes ADH and OXT and transports them to
posterior pituitary gland for release
– Secretes regulatory hormones that control secretory
activity of anterior pituitary gland
– Contains autonomic centers that exert direct control
over adrenal medulla
38
Figure 18–6 Three Mechanisms of Hypothalamic Control over Endocrine Function.
Production of
antidiuretic
hormone (ADH)
and oxytocin (OXT)
Secretion of regulatory
hormones to control
activity of the anterior
lobe of the pituitary gland
Control of
sympathetic
output to adrenal
medulla
HYPOTHALAMUS Preganglionic
motor fibers
Adrenal Gland
InfundibulumAdrenal cortex
Adrenal medulla
Anterior lobe
of pituitary gland
Posterior lobe
of pituitary gland
Hormones secreted by
the anterior lobe control
other endocrine organs
Release of antidiuretic
hormone (ADH) and oxytocin
(OXT) from posterior lobe
Secretion of epinephrine (E)
and norepinephrine (NE)
from adrenal medulla
39
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18-3 The Pituitary Gland
Anterior lobe of pituitary gland
– Also called adenohypophysis
• Hormones “turn on” endocrine glands or support
functions of other organs
• Has three regions
– Pars distalis
– Pars tuberalis
– Pars intermedia
40
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18-3 The Pituitary Gland
Median eminence
– Swelling near attachment of infundibulum
– Where hypothalamic neurons release regulatory
hormones into interstitial fluids
• Hormones then enter bloodstream through
fenestrated capillaries (fenestra = window)
41
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18-3 The Pituitary Gland
Portal vessels
– Blood vessels that link two capillary networks
– Entire complex is a portal system
– Hypophyseal portal system
• Ensures that regulatory hormones reach cells in
anterior pituitary before entering general circulation
42
Figure 18–7 The Hypophyseal Portal System and the Blood Supply to the Pituitary Gland.
Supra-optic nuclei Paraventricular nuclei Neurosecretory neurons
Mammillary
body
The superior hypophyseal artery delivers
blood to a capillary network in the upper
infundibulum.
Optic
chiasm
Capillary network
Infundibulum The portal vessels deliver blood containingregulatory hormones to the capillarynetwork in the anterior lobe of the pituitary.
The inferior hypophyseal artery delivers
blood to the posterior lobe of the pituitary
gland.
Hypophyseal veins carry blood containing
the pituitary hormones to the
cardiovascular system for delivery to the
rest of the body.
Anterior lobe of
the pituitary gland
Capillary network in
the anterior lobe
Posterior lobe of
the pituitary gland
Endocrine cells
43
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18-3 The Pituitary Gland
Hypothalamic control of anterior lobe
– Two classes of hypothalamic regulatory hormones
• Releasing hormones (RH)
– Stimulate synthesis and secretion of one or more
hormones at anterior lobe
• Inhibiting hormones (IH)
– Prevent synthesis and secretion of hormones
from anterior lobe
– Rate of secretion is controlled by negative feedback
44
Figure 18–8a Feedback Control of Endocrine Secretion.
Typical pattern of regulation when multiple endocrine organs are involved
The hypothalamus produces a releasing hormone (RH) to stimulate hormone production by other glands. Homeostatic
control occurs by negative feedback.
HypothalamusKEY
Stimulation
Inhibition
The effects of hypothalamic releasing hormones that follow the typical pattern of
regulation
RH
Pituitary
gland
Releasing
hormone (RH) TRH CRH GnRH
Anterior
lobe
Hormone 1
Negative
feedbackHormone 1
(from pituitary)
Endocrine
target organ
TSH ACTH FSH LH
Endocrine
organ
Hormone 2
Thyroid
gland
Adrenal
cortexTestes Testes Ovaries
Hormone 2
(from endocrine
target organ)
Thyroid
hormonesGlucocorticoids Inhibin
Inhibin
Estrogens
Progesterone
EstrogensAndrogens
Ovaries
a
Target cells
45
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18-3 The Pituitary Gland
Hormones of anterior lobe
– Thyroid-stimulating hormone (TSH)
– Adrenocorticotropic hormone (ACTH)
• Released due to corticotropin-releasing hormone
(CRH)
– Prolactin (PRL)
• Release inhibited by prolactin-inhibiting hormone
(PIH)
• Release stimulated by prolactin-releasing
hormone (PRH)
– Growth hormone (GH), or somatotropin
– Gonadotropins
46
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18-3 The Pituitary Gland
Gonadotropins
– Follicle-stimulating hormone (FSH)
– Luteinizing hormone (LH)
• In females, it induces ovulation and stimulates
secretion of estrogens and progesterone
• In males, it stimulates production of androgens
– Production of FSH and LH is stimulated by
gonadotropin-releasing hormone (GnRH)
– Hypogonadism
• Caused by low production of gonadotropins
47
Figure 18–9 Pituitary Hormones and Their Targets (Part 1 of 2).
Hypothalamus
Direct Control
by Nervous
System
Indirect Control through Release
of Regulatory Hormones
Regulatory hormones are released
into the hypophyseal portal system
for delivery to the anterior lobe of the
pituitary gland
KEY TO PITUITARY HORMONES:
ACTH
TSH
GH
PRL
FSH
LH
MSH
ADH
OXT
Adrenocorticotropic hormone
Thyroid-stimulating hormone
Growth hormone
Prolactin
Follicle-stimulating hormone
Luteinizing hormone
Melanocyte-stimulating hormone
Antidiuretic hormone
Oxytocin
Adrenal
medulla
Adrenal
glandAdrenal
cortex
Anterior lobe of
pituitary gland
ACTH
TSH
Liver
PRL
Somatomedins
LH
GH
Epinephrine and
norepinephrineThyroid
gland
MSH
Glucocorticoids
(cortisol,
corticosterone)
Bone, muscle,
other tissues Mammary
glands
Thyroid
hormones (T3, T4)
Inhibin
Testes
of male
Ovaries
of female
Melanocytes (uncertain
significance in healthy
adults)
Testosterone Estrogen Progesterone Inhibin
FSH
48
Figure 18–8a Feedback Control of Endocrine Secretion.
49
Figure 18–8b Feedback Control of Endocrine Secretion.
Variations on the typical pattern of regulation of endocrine
organs by the hypothalamus and anterior pituitary lobe
The regulation ofprolactin (PRL)production bythe anterior lobe.In this case, thehypothalamusproduces both areleasing hormone(PRH) and aninhibiting hormone(PIH). When one isstimulated, theother is inhibited.
PIH
PRH
Stimulation
Inhibition
Anteriorlobe
PRL
Stimulates
mammary
glands
b
50
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18-3 The Pituitary Gland
Growth hormone stimulates
– Liver cells to release somatomedins that stimulate
tissue growth
• Somatomedins cause skeletal muscle fibers and
other cells to increase uptake of amino acids
– Stem cells in epithelia and connective tissues to divide
– Breakdown of triglycerides in adipocytes, which leads
to glucose-sparing effect
– Breakdown of glycogen by liver cells causing
diabetogenic effect
51
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18-3 The Pituitary Gland
Production of growth hormone is regulated by
– Growth hormone–releasing hormone (GH–RH)
– Growth hormone–inhibiting hormone (GH–IH)
52
Figure 18–8c Feedback Control of Endocrine Secretion.
Variations on the typical pattern of regulation of endocrine
organs by the hypothalamus and anterior pituitary lobe
The regulation of growth
hormone (GH) production
by the anterior lobe.
When GH–RH release is
inhibited, GH–IH release
is stimulated.
GH–IH
GH–RH
Stimulation
Inhibition
Anterior
lobe
GH
Liver
Somatomedins
Stimulate growth of skeletal muscle,
cartilage, and many other tissues
Epithelia,
adipose tissue,
liver
c
53
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18-3 The Pituitary Gland
Pars intermedia
– Secretes melanocyte-stimulating hormone (MSH)
• Stimulates melanin production
– Virtually nonfunctional in adults except in
• Pregnant women
• Those with certain diseases
54
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18-3 The Pituitary Gland
Posterior lobe of the pituitary gland
– Also called neurohypophysis
– Contains unmyelinated axons of hypothalamic neurons
– Supra-optic and paraventricular nuclei manufacture
(respectively)
• Antidiuretic hormone (ADH)
• Oxytocin (OXT)
– Stimulates contraction of uterus during labor
– Promotes ejection of milk after delivery
55
Figure 18–9 Pituitary Hormones and Their Targets (Part 2 of 2).
Hypothalamus
Direct Release
of Hormones
Sensory
stimulation
KEY TO PITUITARY HORMONES:
ACTH
TSH
GH
PRL
FSH
LH
MSH
ADH
OXT
Adrenocorticotropic hormone
Thyroid-stimulating hormone
Growth hormone
Prolactin
Follicle-stimulating hormone
Luteinizing hormone
Melanocyte-stimulating hormone
Antidiuretic hormone
Oxytocin
Posterior lobe
of pituitary gland
ADH
OXTKidneys
Males: Smooth
muscle in ductus
deferens and
prostate gland
Females: Uterine
smooth muscle and
mammary glands
Osmoreceptor
stimulation
56
Figure 18–9 Pituitary Hormones and Their Targets.
Hypothalamus
Direct Control
by Nervous
System
Indirect Control through Release
of Regulatory Hormones
Direct Release
of Hormones
KEY TO PITUITARY HORMONES:
ACTH
TSH
GH
PRL
FSH
LH
MSH
ADH
OXT
Adrenocorticotropic hormone
Thyroid-stimulating hormone
Growth hormone
Prolactin
Follicle-stimulating hormone
Luteinizing hormone
Melanocyte-stimulating hormone
Antidiuretic hormone
Oxytocin
Regulatory hormones are released
into the hypophyseal portal system
for delivery to the anterior lobe of the
pituitary gland
Sensory
stimulation
Adrenal
medulla
Adrenal
glandAdrenal
cortex
Thyroid
gland
Anterior lobe of
pituitary gland
ACTH
TSH
Liver
PRL
Somatomedins
LH
GH
Posterior lobe
of pituitary gland
ADH
OXT
MSH
Kidneys
Males: Smooth
muscle in ductus
deferens and
prostate gland
Females: Uterine
smooth muscle and
mammary glands
Epinephrine and
norepinephrine
Glucocorticoids
(cortisol,
corticosterone)
Bone, muscle,
other tissues
Thyroid
hormones (T3, T4)
Inhibin
Testes
of male
Ovaries
of female
Melanocytes (uncertain
significance in healthy
adults)
Testosterone Estrogen Inhibin
Osmoreceptor
stimulation
Mammary
glands
FSH
Progesterone
57
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18-4 The Thyroid Gland
Thyroid gland
– Lies inferior to thyroid cartilage of larynx
– Consists of two lobes connected by narrow isthmus
• Thyroid follicles
– Hollow spheres lined by cuboidal epithelium
– Surrounded by capillaries
– Cells absorb iodide ions (I–) from blood
– Follicle cavity contains viscous colloid
• C (clear) cells, or parafollicular cells
58
Figure 18–10a Anatomy of the Thyroid Gland.
Hyoid bone
Superior
thyroid artery
Thyroid cartilage
of larynx
Superior
thyroid vein
Common
carotid artery
Right lobe of
thyroid gland
Middle thyroid
vein
Thyrocervical
trunk
Trachea
Outline of
clavicle
Outline of
sternum
Location and anatomy of the thyroid gland
Internal
jugular vein
Cricoid cartilage
of larynx
Left lobe of
thyroid gland
Isthmus of
thyroid gland
Inferior
thyroid artery
Inferior
thyroid
veins
a 59
Figure 18–10b Anatomy of the Thyroid Gland.
Thyroid follicles
The thyroid gland LM × 122
Histological organization of the thyroidb 60
Figure 18–10c Anatomy of the Thyroid Gland.
Capillary
Capsule
Follicle
cavities
Thyroid
follicle
C cell
Cuboidal
epithelium
of follicle
Thyroglobulin
stored in colloid
of follicle
Thyroid
follicle
C cell
Follicles of the thyroid gland LM × 260
Histological details of the thyroid gland showing thyroid follicles and both celltypes in the follicular epithelium ATLAS: Plate 18c
c
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18-4 The Thyroid Gland
Thyroglobulin
– Globular protein synthesized by follicle cells
– Secreted into colloid of thyroid follicles
– Contains the amino acid tyrosine
• The building block of thyroid hormones
Thyroid hormones
– Thyroxine (T4), or tetraiodothyronine
• Contains four iodine atoms
– Triiodothyronine (T3)
• Contains three iodine atoms
62
Figure 18–11a Synthesis and Regulation of Thyroid Hormones.
1
Thyroglobulin
(contains T3 and T4)
4
2
Iodineatoms (I0)
Thyroglobulin
5
Follicle cavity
Iodide ions are absorbed from the digestive tract and
delivered to the thyroid gland by the bloodstream.
2
Endocytosis Iodide ions diffuse to the apical surface of each follicle cell
where they are converted into an atom of iodine (I0). The
tyrosine portion of thyroglobulin bind the iodine atoms.
3
Iodine-containing thyroxine molecules become linked to
form thyroid hormones (T3 and T4)
4
Follicle cells remove thyroglobulin from the follicles by
endocytosis.
Diffusion 5
Lysosomal enzymes break down the thyroglobulin, and the
amino acids and thyroid hormones enter the cytoplasm.
7
CAPILLARY
6
The released T3 and T4 diffuse from the follicle cell into
the bloodstream.
7
A majority of the T3 and T4 bind to transport proteins.
Folliclecavity
Other amino acids
Tyrosine
Lysosomal
digestion
T4
T3
Diffusion
TSH-
sensitive
ion pump1
Follicle cell
Iodide ions (I–)
T4 & T3
The synthesis, storage, and secretion of thyroid hormones.
TBG, transthyretin,
or albumin
3
6
a
63
Figure 18–11b Synthesis and Regulation of Thyroid Hormones.
HOMEOSTASISHomeostasis
DISTURBED BY
DECREASING
T3 and T4
concentrations
in blood or low
body temperature
Normal T3 and T4 concentrations,
normal body temperatureHomeostasis
RESTORED BY
STIMULUS
Receptor
Hypothalamus
RESTOREDINCREASING
T3 and
T4 concentrations
in blood
Anterior lobe T3 and T4
concentrations increase
in blood and body
temperature rises
TRH Effector
Anterior
lobe
TSH
Anterior
lobe Thyroid
gland
Thyroid follicles
release T3 and T4
Hypothalamus
releases TRHAnterior lobe
releases TSH
The regulation of thyroid secretion.b
64
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18-4 The Thyroid Gland
Thyroid-binding globulins (TBGs)
– Proteins that bind about 75 percent of T4 and 70
percent of T3 entering the bloodstream
Transthyretin and albumin
– Bind most of the remaining thyroid hormones
About 0.3 percent of T3 and 0.03 percent of T4 remain
unbound and free to diffuse into tissues
65
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18-4 The Thyroid Gland
Thyroid-stimulating hormone (TSH)
– Absence causes thyroid follicles to become inactive
• Neither synthesis nor secretion occurs
– Binds to plasma membrane receptors
• Activates key enzymes in thyroid hormone
production
66
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18-4 The Thyroid Gland
Thyroid hormones
– Affect almost every cell in body
– Enter target cells by transport system
– Bind to receptors
• In cytoplasm
• On surfaces of mitochondria
• In nucleus
– In children, essential to normal development of
skeletal, muscular, and nervous systems
67
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18-4 The Thyroid Gland
Thyroid hormones activate genes involved in glycolysis
and ATP production
– Results in calorigenic effect
• Increased energy consumption and heat generation
of cells
• Responsible for strong, immediate, and short-lived
increase in rate of cellular metabolism
68
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18-4 The Thyroid Gland
C cells
– Produce calcitonin (CT)
• Helps regulate concentrations of Ca2+ in body fluids
• Stimulates Ca2+ excretion by kidneys
• Prevents Ca2+ absorption by digestive tract
69
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18-4 The Thyroid Gland
Effects of thyroid hormones
– Elevate oxygen and energy consumption; in children,
may cause rise in body temperature
– Increase heart rate and force of contraction
– Increase sensitivity to sympathetic stimulation
– Maintain normal sensitivity of respiratory centers to
oxygen and carbon dioxide concentrations
– Stimulate red blood cell formation
– Stimulate activity in other endocrine tissues
– Accelerate turnover of minerals in bone
70
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18-5 Parathyroid Glands
Parathyroid glands
– Two pairs
– Embedded in posterior surface of thyroid gland
– Altogether, the four glands weigh 1.6 g
Parathyroid hormone (PTH) or parathormone
– Secreted by parathyroid (principal) cells in response
to low concentrations of Ca2+ in blood
– Antagonist for calcitonin
71
Figure 18–12a Anatomy of the Parathyroid Glands.
Left lobe of
thyroid gland
Parathyroid
glands
Thyroid gland, posterior view.
The location of the parathyroid glands
on the posterior surface of the thyroid
lobes. (The thyroid lobes are located
anterior to the trachea.)
a
72
Figure 18–12b Anatomy of the Parathyroid Glands.
Blood vessel
Connectivetissue capsuleof parathyroid
gland
Thyroid
follicle
Parathyroid gland
Both parathyroid and thyroid tissues.
LM × 94
b
73
Figure 18–12c Anatomy of the Parathyroid Glands.
Parathyroid(principal)cells
Oxyphil cells
Parathyroid cells and oxyphil cells
Parathyroid gland cells.
LM × 600
c
74
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18-5 Parathyroid Glands
Major effects of parathyroid hormone
– Stimulates osteoclasts
• Accelerates mineral turnover and Ca2+ release
– Enhances reabsorption of Ca2+ by kidneys, reducing
urinary losses
– Stimulates formation and secretion of calcitriol by
kidneys
75
Figure 18–13 Homeostatic Regulation of the Blood Calcium Ion Concentration (Part 1 of 2) .
76
Figure 18–13 Homeostatic Regulation of the Blood Calcium Ion Concentration (Part 2 of 2) .
77
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18-6 Adrenal Glands
Adrenal glands
– Lie along superior border of each kidney
– Superficial adrenal cortex
• Stores lipids, especially cholesterol and fatty acids
• Manufactures steroid hormones (corticosteroids)
– Inner adrenal medulla
• Secretory activities controlled by sympathetic
division of ANS
• Produces epinephrine and norepinephrine
(catecholamines)
78
Figure 18–14a The Adrenal Gland and Adrenal Hormones.
Right superior
adrenal arteries
Celiac trunk
Right adrenal gland
Right middle
adrenal artery
Right inferior
adrenal artery
Right renal artery
Right renal vein
Right and left inferior
phrenic arteries
Left adrenal gland
Left middle
adrenal artery
Left inferior
adrenal arteries
Left adrenal vein
Left renal artery
Left renal vein
Superior
mesenteric artery
Abdominal aorta
Inferior vena cava
A superficial view of the kidneys
and adrenal glands
a
79
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18-6 Adrenal Glands
Adrenal cortex
– Subdivided into three zones
• Outer zona glomerulosa
• Middle zona fasciculata
• Inner zona reticularis
80
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18-6 Adrenal Glands
Zona glomerulosa
– Outer region of adrenal cortex
– Produces mineralocorticoids (e.g., aldosterone)
– Aldosterone
• Stimulates conservation of sodium ions and
elimination of potassium ions
• Increases sensitivity of salt receptors in taste buds
• Secreted in response to
– Drop in blood Na+, blood volume, or blood
pressure
– Rise in blood K+ concentration
81
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18-6 Adrenal Glands
Zona fasciculata
– Produces glucocorticoids
• Example: cortisol, corticosterone, and cortisone
• Secretion is regulated by negative feedback
– Glucocorticoids have inhibitory effect on production of
• Corticotropin-releasing hormone (CRH) in
hypothalamus
• ACTH in anterior pituitary
82
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18-6 Adrenal Glands
Effects of glucocorticoids
– Accelerate glucose synthesis and glycogen formation,
especially in liver
– Have anti-inflammatory effects
• Inhibit activities of white blood cells and other
components of immune system
83
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18-6 Adrenal Glands
Zona reticularis
– Branching network of endocrine cells
– Forms narrow band bordering each adrenal medulla
– Produces small quantities of androgens under
stimulation by ACTH
• Some are converted to estrogens in bloodstream
• Stimulate development of pubic hair before puberty
84
Figure 18–14b The Adrenal Gland and Adrenal Hormones.
Capsule
Cortex
Medulla
An adrenal glandin section
b
85
Figure 18–14c The Adrenal Gland and Adrenal Hormones.
The Adrenal Hormones
Region/Zone
Adrenal capsule
Zona
glomerulosa
Hormones
Mineralocorticoids,primarilyaldosterone
Primary
Target
Kidneys
Hormonal Effects
Increase renal reabsorptionof Na+ and water (especiallyin the presence of ADH),and accelerate urinary lossof K+
Increase rates of glucoseand glycogen formationby the liver; release ofamino acids from skeletalmuscles, and lipids fromadipose tissues; promoteperipheral utilization oflipids; anti-inflammatoryeffects
Regulatory Control
Stimulated by angiotensin II,elevated blood K+ or fall inblood Na+; inhibited by ANPand BNP
Stimulated by ACTH fromthe anterior lobe of thepituitary gland
Zona
fasciculata
Adrenal
cortex
Glucocorticoids
(cortisol, corti-
costerone, and
cortisone)
Most cells
Androgens
Zona
reticularis
Most cells Adrenal androgens stimulatethe development of pubichair in boys and girls beforepuberty.
Increases cardiac activity,blood pressure, glycogenbreakdown, blood glucoselevels; releases lipids byadipose tissue
Stimulated by sympathetic
preganglionic fibers
Epinephrine (E),
norepinephrine
(NE)
Adrenal
medulla
Adrenal gland LM × 140
Most cells
The major regions and zones of an adrenal gland and the hormones they produce
Androgen secretion
is stimulated by
ACTH.
c
86
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18-6 Adrenal Glands
Adrenal medulla
– Contains two types of secretory cells
• One produces epinephrine (E)
– 75–80 percent of medullary secretion
• The other produces norepinephrine (NE)
– 20–25 percent of medullary secretion
87
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18-6 Adrenal Glands
Results of activation of adrenal medulla
– In skeletal muscles, E and NE trigger mobilization of
glycogen reserves
• And accelerate breakdown of glucose
– In adipose tissue, stored fats are broken down into fatty
acids
– In the liver, glycogen molecules are broken down
– In the heart, stimulation of β1 receptors speeds and
strengthens cardiac muscle contraction
88
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18-7 Pineal Gland
Pineal gland
– Lies in posterior portion of roof of third ventricle
– Contains pinealocytes
• Synthesize hormone melatonin
– Functions of melatonin
• Influence circadian rhythms
• Inhibit reproductive functions
• Protect against damage by free radicals
89
Figure 18–15 Anatomy of the Pineal Gland.
Pinealocytes
Pineal gland LM × 280
90
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18-8 Pancreas
Pancreas
– Large gland
– Lies in loop between inferior border of stomach and
proximal portion of small intestine
– Mostly retroperitoneal
– Contains exocrine and endocrine cells
91
Figure 18–16a Anatomy of the Pancreas.
Common
bile duct
Accessorypancreatic
duct
Head of
pancreas
Pancreatic
duct
Body of
pancreasLobule Tail
Small
intestine
(duodenum)
The gross anatomy of the pancreasa
92
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18-8 Pancreas
Exocrine pancreas
– Consists of clusters of gland cells called pancreatic
acini and their attached ducts
– Takes up roughly 99 percent of pancreatic volume
– Gland and duct cells secrete alkaline, enzyme-rich fluid
• Passes through a network of ducts to lumen of
digestive tract
93
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18-8 Pancreas
Endocrine pancreas
– Consists of cells that form clusters known as
pancreatic islets (islets of Langerhans)
• Alpha (α) cells produce glucagon
• Beta (β) cells produce insulin
• Delta (δ) cells produce peptide hormone identical to
GH–IH
• Pancreatic polypeptide cells (PP cells) produce
pancreatic polypeptide (PP)
94
Figure 18–16b Anatomy of the Pancreas.
Pancreatic islet
(islet of Langerhans)
Capillary
Pancreatic islet LM × 400
A pancreatic islet surrounded by
exocrine cells
b
Pancreatic acini
(clusters ofexocrine cells)
95
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18-8 Pancreas
When blood glucose level increases
– Beta cells secrete insulin
• Stimulating transport of glucose into target cells
When blood glucose level decreases
– Alpha cells secrete glucagon
• Stimulating glycogen breakdown and glucose
release by liver
96
Figure 18–17 Homeostatic Regulation of the Blood Glucose Concentration (Part 1 of 2).
97
Figure 18–17 Homeostatic Regulation of the Blood Glucose Concentration (Part 2 of 2).
98
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18-8 Pancreas
Insulin
– Peptide hormone released by beta cells
– Effects on target cells
• Accelerating glucose uptake
• Accelerating glucose use and enhancing ATP
production
• Stimulating glycogen formation
• Stimulating amino acid absorption and protein
synthesis
• Stimulating triglyceride formation in adipocytes
99
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18-8 Pancreas
Glucagon
– Released by alpha cells
– Mobilizes energy reserves
– Effects on target cells
• Stimulating breakdown of glycogen in skeletal
muscle fibers and liver cells
• Stimulating breakdown of triglycerides in adipocytes
• Stimulating production and release of glucose in
liver cells (gluconeogenesis)
100
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18-8 Pancreas
Hyperglycemia
– Abnormally high glucose levels in the blood
Diabetes mellitus
– Characterized by high glucose concentrations that
overwhelm reabsorption capabilities of kidneys
– Glucose appears in urine
– Polyuria
• Urine volume becomes excessive
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18-8 Pancreas
Type 1 diabetes mellitus
– Characterized by inadequate insulin production by
pancreatic beta cells
– Patients require daily injections or continuous infusion
of insulin
– Approximately 5 percent of cases
– Usually develops in children and young adults
102
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18-8 Pancreas
Type 2 diabetes mellitus
– Most common form
– Usually, normal amounts of insulin are produced, at
least initially
• Tissues do not respond properly (insulin resistance)
– Associated with obesity
• Weight loss can be an effective treatment
103
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18-8 Pancreas
Complications of untreated or poorly managed diabetes
mellitus include
– Kidney degeneration
– Retinal damage (diabetic retinopathy)
• May lead to blindness
– Early heart attacks (3–5 times more likely)
– Peripheral nerve problems (diabetic neuropathies)
– Peripheral tissue damage due to reduced blood flow
• Tissue death, ulceration, infection, and amputation
104
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18-9 Secondary Endocrine Functions
Organs with secondary endocrine functions
– Intestines (digestive system)
– Kidneys (urinary system)
– Heart (cardiovascular system)
– Thymus (lymphatic system)
– Gonads (reproductive system)
105
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18-9 Secondary Endocrine Functions
Intestines
– Release hormones that coordinate digestive activities
Kidneys
– Release the hormones calcitriol and erythropoietin
(EPO)
– Release the enzyme renin
• Renin converts angiotensinogen to angiotensin I
• In the lungs, angiotensin-converting enzyme
converts angiotensin I to angiotensin II
106
Figure 18–19a Endocrine Functions of the Kidneys.
SunlightFood
Cholesterol
Epidermis
Cholecalciferol
Dietarycholecalciferol
Liver
Intermediateform
Parathyroid glands
Digestivetract
Stimulation ofcalcium and
phosphate ionabsorption
PTH
Calcitriol
Kidney
The production of calcitriola 107
Figure 18–19b Endocrine Functions of the Kidneys.
Homeostasis
DISTURBED BY
DECREASING
blood pressure
and
volume
HOMEOSTASISNormal blood pressure and volume Homeostasis
RESTORED BY
INCREASING
blood pressure
and
volume
STIMULUS
Receptor
Kidney
RESTORED
Increase in blood
pressure and volume
Endocrine Response
of Kidneys
Decreasing
renal blood
flow and O2
Increased fluid intake
and retention
Increased
red blood cell
production
Erythropoietin (EPO)
is released
Renin is released
Aldosterone secreted
ADH secreted
Stimulation of thirst
Angiotensinogen Angiotensin IACE
Angiotensin II
The release of renin and erythropoietin, and an overview of the renin-angiotensin-aldosterone
system beginning with the activation of angiotensinogen by reninb
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18-9 Secondary Endocrine Functions
Heart
– Produces natriuretic peptides (ANP and BNP)
• When blood volume becomes excessive
• Actions opposes those of angiotensin II
• Resulting in reduction in blood volume and blood
pressure
Thymus
– Produces thymosin (blend of several hormones)
• Promotes development and maturation of
lymphocytes
109
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18-9 Secondary Endocrine Functions
Testes
– Interstitial endocrine cells produce androgens
• Testosterone is an important androgen
– Nurse cells (Sertoli cells)
• Support differentiation and physical maturation of
sperm
• Secrete inhibin for negative feedback
110
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18-9 Secondary Endocrine Functions
Ovaries
– Produce estrogens
• Principal estrogen is estradiol
– After ovulation, follicle cells
• Reorganize into corpus luteum
• Release estrogens and progesterone
111
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18-9 Secondary Endocrine Functions
Adipose tissue
– Produces leptin (a peptide hormone)
• Provides feedback control of appetite
• Maintains normal levels of GnRH and gonadotropin
synthesis
112
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18-10 Hormone Interactions
When a cell receives instructions from two hormones at
the same time, four outcomes are possible
– Antagonistic effect
• Result depends on balance between two hormones
– Synergistic effect
• Additive effect
– Permissive effect
• One hormone is needed for another to produce
effect
– Integrative effect
• Hormones produce different but complementary
results
113
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18-10 Hormone Interactions
Hormones important to growth
– Growth hormone
– Thyroid hormones
– Insulin
– Parathyroid hormone and calcitriol
– Reproductive hormones
114
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18-10 Hormone Interactions
Growth hormone (GH)
– In children
• Supports muscular and skeletal development
– In adults
• Maintains normal blood glucose concentrations
• Mobilizes lipid reserves
115
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18-10 Hormone Interactions
Thyroid hormones
– If absent during fetal development or for first year after
birth
• Nervous system fails to develop normally
• Developmental delay results
– If T4 concentrations decline before puberty
• Normal skeletal development does not continue
116
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18-10 Hormone Interactions
Insulin
– Allows passage of glucose and amino acids across
plasma membranes
– Important for growing cells
Parathyroid hormone (PTH) and calcitriol
– Promote absorption of calcium salts from bloodstream
for deposition in bone
– Inadequate levels result in weak, flexible bones
117
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18-10 Hormone Interactions
Reproductive hormones
– Androgens in males, estrogens in females
– Stimulate cell growth and differentiation in target
tissues
– Produce gender-related differences in
• Skeletal proportions
• Secondary sex characteristics
118
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18-10 Hormone Interactions
Stress
– Any condition that threatens homeostasis
– General adaptation syndrome (GAS)
• Also called stress response
• How body responds to stress-causing factors
• Divided into three phases
– Alarm phase
– Resistance phase
– Exhaustion phase
119
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18-10 Hormone Interactions
General adaptation syndrome
– Alarm phase
• Immediate response to stress
• Directed by sympathetic division of ANS
• Energy reserves (mainly glucose) are mobilized
• Body prepares “fight or flight” responses
• Epinephrine is dominant hormone
120
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18-10 Hormone Interactions
General adaptation syndrome
– Resistance phase
• Occurs if stress lasts longer than a few hours
• May last for weeks or months
• Glucocorticoids are dominant hormones
• Lipids and amino acids are mobilized for energy
• Glucose is conserved for use by nervous tissue
121
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18-10 Hormone Interactions
General adaptation syndrome
– Exhaustion phase
• Begins when homeostatic regulation breaks down
• Drop in K+ levels due to aldosterone produced in
resistance phase
• Failure of one or more organ systems will be fatal
122
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18-10 Hormone Interactions
Hormone changes
– Can affect behavior, intellectual capabilities, memory,
learning, and emotional states
Few functional changes occur with age
– Reproductive hormones decline in concentration
– Some endocrine tissues become less responsive to
stimulation
123
Figure 18–21 Integration of the ENDOCRINE system with the other body systems presented so far.
Integumentary System
• The endocrine system secretes sex
hormones that stimulate sebaceous
gland activity, influence hair growth,
fat distribution, and apocrine sweat
gland activity; PRL that stimulates
development of mammary glands;
adrenal hormones that alter dermal
blood flow; MSH that stimulates
melanocyte activity
Nervous System
• The Nervous System produces
hypothalamic hormones that directly
control pituitary secretions and
indirectly control secretions of other
endocrine organs; controls adrenal
medulla; secretes ADH and oxytocin
• The endocrine system secretes
several hormones that affect neural
metabolism and brain development;
hormones that help regulate fluid and
electrolyte balance; reproductive
hormones that influence CNS
development and behaviors
Skeletal System
• The Skeletal System protects
endocrine organs, especially in brain,
chest, and pelvic cavity
• The endocrine system regulates
skeletal growth with several
hormones; calcium homeostasis
regulated primarily by parathyroid
hormone; sex hormones speed
growth and closure of epiphyseal
cartilages at puberty and help
maintain bone mass in adults
Endocrine System
The endocrine system provides
long-term regulation and adjustments
of homeostatic mechanisms that affect
many body functions. It:
• regulates fluid and electrolyte
balance
• regulates cell and tissue metabolism
• regulates growth and development
• regulates reproductive functions
• responds to stressful stimuli through
the general adaptation syndrome
(GAS)
Muscular System
• The Muscular System provides
protection for some endocrine
organs
• The endocrine system secretes
hormones that adjust muscle
metabolism, energy production,
and growth; regulate calcium and
phosphate levels in body fluids;
speed skeletal muscle growth
124
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