Human Physiology - Maryville University
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Transcript Human Physiology - Maryville University
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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