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Chapter 11
Endocrine Glands Secretion & Action of Hormones
11-1
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Chapter 11 Outline
Overview
Chemical
Classification of Hormones
Hormonal Actions & Interactions
Mechanisms of Hormone Action
Pituitary Gland
Adrenal Gland
Thyroid Gland
Islets of Langerhans
Miscellaneous Glands & Hormone
Autocrine & Paracrine Regulation
11-2
Overview
11-3
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Endocrine Glands
 Are
ductless & secrete
hormones into
bloodstream
 Hormones go to target
cells that contain
receptor proteins for it
 Neurohormones are
secreted into blood by
specialized neurons
 Hormones affect
metabolism of targets
Fig 11.1
11-4
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11-5
Chemical Classification of
Hormones
11-6
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Chemical Classification of Hormones
 Amine
hormones are derived from tyrosine or tryptophan
Include
NE, Epi, thyroxine, melatonin
 Polypeptide/protein
hormones are chains of amino acids
 Include ADH, GH, insulin, oxytocin, glucagon, ACTH, PTH
 Glycoproteins include LH, FSH, TSH
 Steroids are lipids derived from cholesterol
 Include testosterone, estrogen, progesterone & cortisol
11-7
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Fig 11.2
11-8
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Chemical Classification of Hormones continued
 Steroid
& thyroid hormones are lipids
 Can diffuse into target cells
 The 2 major thyroid hormones are shown in Fig 11.3
11-9
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Prohormones & Prehormones
Prohormones
are precursors of hormones
E.g. proinsulin
Prehormones are precursors of prohormones
E.g. preproinsulin
Some hormones are inactive until activated by target
cells
E.g. thyroxine (T4) is inactive until converted to T3 in
target cells
11-10
Hormonal Actions & Interactions
11-11
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Common Aspects of Neural & Endocrine
Regulation
Both
NS & endocrine system use chemicals to
communicate
Difference between NTs & hormones is transport in
blood & more diversity of effects in hormone targets
Some chemicals are used as hormones & NTs
Targets for both NTs & hormones must have specific
receptor proteins
Must be way to rapidly inactivate both
11-12
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Hormone Interactions
A tissue
usually responds to # of hormones
2 hormones are synergistic if work together to produce
an effect
Produce a larger effect together than individual
effects added together
A hormone has permissive effect if it enhances
responsiveness of a target organ to 2nd hormone
If action of 1 hormone inhibits effect of another, it is
antagonistic
11-13
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Hormone Levels & Tissue Responses
Half-life
is time required for blood level to be reduced
by half
Ranges from mins to hrs for most (days for thyroid
hormones)
Normal tissue responses are produced only when
hormones are in physiological range
High (pharmacological) doses can cause # of side
effects
Probably by binding to receptors of other hormones
11-14
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Hormone Levels & Tissue Responses continued
Priming
effect (upregulation) occurs when a hormone
induces more of its own receptors in target cells
Results in greater response in target cell
Desensitization (downregulation) occurs after long
exposure to high levels of polypeptide hormone
Subsequent exposure to this hormone produces a
lesser response
Due to decrease in # of receptors on targets
Most peptide hormones have pulsatile secretion
which prevents downregulation
11-15
Mechanisms of Hormone Action
11-16
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Mechanisms of Hormone Action
Target
cell receptors show specificity, high affinity, &
low capacity for a hormone
Lipid hormones have receptors in target's cytoplasm
&/or nucleus because can diffuse thru plasma
membrane
Receptors for water-solubles are on surface of target
cell
11-17
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Hormones That Bind to Nuclear Receptor
Proteins
 Lipid
hormones travel in
blood attached to carrier
proteins
 They dissociate from
carriers to pass thru
plasma membrane of
target
 Receptors are
called nuclear
hormone receptors
Fig 11.4
11-18
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Nuclear Hormone Receptors
 Serve
as transcription factors when bound to hormone ligands
 Activate transcription
 Constitute a "superfamily" composed of steroid family & thyroid
hormone family (which includes vitamin D & retinoic acid)
11-19
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Nuclear Hormone Receptors
 Have
ligand (hormone)-binding & DNA-binding domains
 Binds hormone & translocates to nucleus
 Binds to hormone-response element (HRE) on DNA located
adjacent to target gene
Fig 11.5
11-20
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Mechanisms of Steroid Hormones
 HRE
consists of 2 half-
sites
 2 ligand-bound receptors
have to bind to each HRE
(dimerization)
 This stimulates
transcription of target
gene
Fig 11.5
11-21
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Mechanism of Thyroid Hormone Action
Thyroid
secretes 90% T4 (thyroxine) & 10% T3
99.96% of T4 in blood is bound to carrier protein
(thyroid binding globulin - TBG)
Only free can enter cells, so bound is reservoir
T4 converted to T3 inside cell
T3 binds to receptor protein located in nucleus
11-22
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Mechanism of Thyroid Hormone Action
continued
 T3
& receptor bind to 1
half-site
 Other half-site binds
retinoic acid
 Two partners form
heterodimer that
activates HRE
 Stimulates
transcription of
target gene
Fig 11.7
11-23
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Hormones That Use 2nd Messengers
Water
soluble hormones use cell surface receptors
because cannot pass through plasma membrane
Actions are mediated by 2nd messengers
Hormone is extracellular signal; 2nd messenger
carries signal from receptor to inside of cell
11-24
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Adenylate Cyclase-cAMP
 Mediates
effects of many polypeptide & glycoprotein hormones
 Hormone binds to receptor causing dissociation of a G-protein
subunit
Fig 11.8
11-25
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Adenylate Cyclase-cAMP continued
 G-protein
subunit binds to & activates adenylate cyclase
 Which converts ATP into cAMP
 cAMP attaches to inhibitory subunit of protein kinase
Fig 11.8
11-26
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Adenylate Cyclase-cAMP continued



Inhibitory subunit dissociates, activating protein kinase
Which phosphorylates enzymes that produce
hormone’s effects
cAMP inactivated by phosphodiesterase
Fig 11.8
11-27
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Phospholipase-C-Ca2+
 Serves
as 2nd messenger system for some hormones
 Hormone binds to surface receptor, activates G-protein, which
activates phospholipase C
Fig 11.9
11-28
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Phospholipase-C-Ca2+
 Phospholipase
C splits a membrane phospholipid into 2nd
messengers IP3 & DAG
 IP3 diffuses through cytoplasm to ER
 Causing Ca2+ channels to open
Fig 11.9
11-29
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Phospholipase-C-Ca2+ continued
Ca2+
diffuses into cytoplasm & binds to & activates
calmodulin
Ca2+-Calmodulin activates protein kinases which
phosphorylate enzymes that produce hormone's
effects
11-30
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Epi Can Act Via Two 2nd Messengers
Fig 11.10
11-31
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Tyrosine Kinase 2nd Messenger System
 Is
used by insulin &
many growth factors to
cause cellular effects
 Surface receptor is
tyrosine kinase
 Consists of 2 units
that form active
dimer when insulin
binds
Fig 11.11
11-32
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Tyrosine Kinase 2nd Messenger System
 Activated
tyrosine
kinase
phosphorylates
signaling molecules
that induce
hormone/growth
factor effects
Fig 11.11
11-33
Pituitary Gland
11-34
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Pituitary Gland
 Pituitary
gland is located beneath hypothalamus at base of
forebrain
Fig 8.16
11-35
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Pituitary Gland continued
 Is
structurally &
functionally divided into
anterior & posterior lobes
 Hangs below
hypothalamus by
infundibulum
 Anterior produces own
hormones
 Controlled by
hypothalamus
 Posterior stores &
releases hormones made
in hypothalamus
Fig 11.12
11-36
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Anterior Pituitary
 Secretes
6 trophic
hormones that
maintain size of
targets
 High blood levels
cause target to
hypertrophy
 Low levels
cause atrophy
11-37
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Anterior Pituitary continued
 Growth
hormone (GH) promotes growth, protein synthesis, &
movement of amino acids into cells
 Thyroid stimulating hormone (TSH) stimulates thyroid to
produce & secrete T4 & T3
Adrenocorticotrophic
hormone (ACTH) stimulates
adrenal cortex to secrete cortisol, aldosterone
Follicle stimulating hormone (FSH) stimulates growth
of ovarian follicles & sperm production
Luteinizing hormone (LH) causes ovulation & secretion
of testosterone in testes
Prolactin (PRL) stimulates milk production by
mammary glands
11-38
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Anterior Pituitary continued
Release
of A. Pit. hormones is controlled by
hypothalamic releasing & inhibiting factors & by
feedback from levels of target gland hormones
11-39
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Anterior Pituitary continued
 Releasing
& inhibiting
hormones from
hypothalamus are released
from axon endings into
capillary bed in median
eminence
 Carried by
hypothalamohypophyseal portal
system directly to
another capillary bed in
A. Pit.
 Diffuse into A. Pit. &
regulate secretion of
its hormones
Fig 11.15
11-40
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Feedback Control of Anterior Pituitary
 Involves
short feedback
loop in which retrograde
flow of blood & hormones
from A. Pit. to
hypothalamus inhibits
secretion of releasing
hormone
 Involves negative
feedback of target gland
hormones
 & during menstrual cycle,
estrogen stimulates “LH
surge” by positive
feedback
Fig 11.17
11-41
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Higher Brain Function & Anterior Pituitary
Secretion
Hypothalamus
receives input from higher brain centers
that can affect A. Pit. secretion
E.g. psychological stress affects circadian rhythms,
menstrual cycle, & adrenal hormones
11-42
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Posterior Pituitary
Stores
& releases 2 hormones produced in
hypothalamus:
Antidiuretic hormone (ADH/vasopressin) which
promotes H20 conservation by kidneys
Oxytocin which stimulates contractions of uterus
during parturition
& contractions of mammary gland alveoli for milkejection reflex
11-43
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Hypothalamic Control of Posterior Pituitary
 Supraoptic
nuclei of
hypothalamus produce
ADH
 Paraventricular nuclei
produce oxytocin
 Both transported along
hypothalamohypophyseal tract to
posterior pituitary
 Release controlled in
hypothalamus by
neuroendocrine reflexes
Fig 11.13
11-44
Adrenal Gland
11-45
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Adrenal Glands
Sit
on top of
kidneys
Each consists of
outer cortex & inner
medulla
2 arise differently
during
development
Fig 11.18
11-46
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Adrenal Glands
Medulla
synthesizes & secretes 80% Epi & 20% NE
Controlled by sympathetic
Cortex is controlled by ACTH & secretes:
Cortisol which inhibits glucose utilization &
stimulates gluconeogenesis
Aldosterone which stimulate kidneys to reabsorb
Na+ and secrete K+
& some supplementary sex steroids
11-47
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Adrenal Cortex
Fig 11.19
11-48
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Adrenal Medulla
Hormonal
effects of Epi last 10X longer than NE
Innervated by preganglionic Symp fibers
Activated during "fight or flight" response
Causes:
Increased respiratory rate
Increased HR & cardiac output
General vasoconstriction which increases venous
return
Glycogenolysis & lipolysis
11-49
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Stress & the Adrenal Gland
 Stress
induces a nonspecific response
called general
adaptation syndrome
(GAS)
 Causes ACTH &
cortisol release
 Often affects
physiology
negatively
Fig 11.20
11-50
Thyroid Gland
11-51
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Thyroid Gland
Is
located just below
the larynx
Secretes T4 & T3 which
set BMR & are needed
for growth,
development
Fig 11.21
11-52
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Thyroid Gland
 Consists
of microscopic thyroid follicles
 Outer layer is follicle cells that synthesize T4
 Interior filled with colloid, a protein-rich fluid
11-53
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Production of Thyroid Hormones
(I-) in blood is
actively transported into
follicles & secreted into
colloid
 Where it is oxidized to
iodine (I2) & attached to
tyrosines of thyroglobulin
 A large storage
molecule for T4 & T3
 TSH stimulates
hydrolysis of T4 & T3s
from thyroglobulin &
then secretion
 Iodide
Fig 11.23
11-54
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Diseases of the Thyroid - Goiter
 In
absence of sufficient
dietary iodide, T4 & T3
cannot be made & levels
are low
 Low T4 & T3 don’t
provide negative
feedback & TSH levels
go up
 Because TSH is a
trophic hormone,
thyroid gland grows
 Resulting in a goiter
Fig 11.25
11-55
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Diseases of the Thyroid - Hypothyroidism
People
with inadequate T4 & T3 levels are hypothyroid
Have low BMR, weight gain, lethargy, cold
intolerance
& myxedema = puffy face, hands, feet
During fetal development hypothyroidism can cause
cretenism (severe mental retardation)
11-56
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Diseases of the Thyroid - Hyperthyroidism
Goiters
are also produced by Grave's disease
Autoimmune disease where antibodies act like TSH
& stimulate thyroid gland to grow & oversecrete =
hyperthyroidism
Characterized by exopthalmos, weight loss, heat
intolerance, irritability, high BMR
11-57
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11-58
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Parathyroid Glands
Are
4 glands embedded
in lateral lobes of
thyroid gland
Secrete Parathyroid
hormone (PTH)
Most important
hormone for control
of blood Ca2+ levels
Fig 11.28
11-59
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Parathyroid Hormone
 Release
stimulated by
decreased blood Ca2+
 Acts on bones, kidney, &
intestines to increase
blood Ca2+ levels
Fig 11.29
11-60
Islets of Langerhans
11-61
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Islets of Langerhans
Are
scattered clusters of endocrine cells in pancreas
Contain alpha & beta cells
Fig 11.30
11-62
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Islets of Langerhans continued
Alphas
secrete glucagon in response to low blood
glucose
Stimulates glycogenolysis & lipolysis
Increases blood glucose
11-63
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Islets of Langerhans continued
 Betas
secrete insulin in
response to low blood
glucose
 Promotes entry of
glucose into cells
 & conversion of
glucose into glycogen
& fat
 Decreases blood
glucose
Fig 11.31
11-64
Miscellaneous Glands &
Hormones
11-65
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Pineal Gland
 Is
located in basal
forebrain near
thalamus
 Secretes melatonin
in response to
activity of
suprachiasmatic
nucleus (SCN) of
hypothalamus
Fig 11.32
11-66
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Pineal Gland continued
SCN
is primary timing center for circadian rhythms
Reset by daily light/dark changes
Melatonin is involved in aligning physiology with
sleep/wake cycle & seasons
Secreted at night & is inhibited by light
Inhibits GnRH (antigonadotropic) in many animals
11-67
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Thymus
 Is
located around
trachea below thyroid
 Produces T cells of
immune system &
hormones that
stimulate them
Fig 11.33
11-68
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Sex & Reproductive Hormones
Gonads
(testes & ovaries) secrete steroid hormones
testosterone, estrogen, & progesterone
Placenta secretes estrogen, progesterone, hCG, and
somatomammotropin
11-69
Autocrine & Paracrine
Regulation
11-70
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Autocrine & Paracrine Regulation
Autocrine
regulators are produced & act within same
tissue of an organ
All autocrines control gene expression in target cells
Paracrine regulators are autocrines that are
produced within one tissue & act on different tissue
in same organ.
Autocrines & paracrines include:
Cytokines (lymphokines, interleukins)
Growth factors (promote growth & cell division)
Neutrophins (provides trophic support for normal
& regenerating neurons)
11-71
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Prostaglandins (PGs)
 Are
produced in almost every organ
 Belong to eicosanoid family -- all derived from arachidonic acid
of plasma membrane
Fig 11.34
11-72
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Prostaglandins (PGs) continued
Have
wide variety of functions
Different PGs may exert antagonistic effects in
tissues
Some promote smooth muscle contraction &
some relaxation
Some promote clotting; some inhibit
Promotes inflammatory process of immune system
Plays role in ovulation
Inhibits gastric secretion in digestive system
11-73
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Prostaglandins (PGs) continued
 Cyclooxygenase
(COX) 1 & 2 are involved in PG synthesis (Fig
11.34)
 Are targets of a number of inhibitory non-steroidal antiinflammatory drugs (NSAIDs)
 Aspirin, indomethacin, ibuprofen inhibit both COX 1 & 2
thereby producing side effects
 Celebrex & Vioxx only inhibit COX 2 & thus have few side
effects
11-74