CHAPTER 50
ENDOCRINE
SYSTEMS
Prepared by
Brenda Leady, University of Toledo
Copyright (c) The McGraw-Hill
Companies, Inc. Permission required
for reproduction or display.
1
Endocrine system is not composed of a
small number of physically connected
tissues and organs
 Nearly all cells release chemical signals
(hormones)
 Some hormone producing cells packaged
in discrete glands- endocrine glands
 Hormones effects can occur in seconds or
hours and may last a few minutes or
several days

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3
3 classes of hormones
1.
Amines

2.
Proteins/ peptides

3.
Derived from tyrosine or tryptophan
Most hormones
Steroids

Cholesterol derivatives, less soluble in
water, use carriers
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Hormone receptors



Only cells with the proper receptors can respond
to the hormone
Receptors bind noncovalently and reversibly
with hormone
Subtypes or isoforms of receptors allow the
same hormone to perform more than one action
 Low
hormone amount has a different effect than a
high amount
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Water-soluble hormone receptors

Receptors on the plasma membrane
 Amine
and protein/peptide hormones (except
thyroid hormone)
Binding initiates a cascade culminating in
intracellular signaling
 Signaling pathways

 Rapid, occurring in seconds
 Involve activity of enzymes
 A single signaling molecule results
in the
production of many intracellular messages
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Lipid hormone receptors
Receptors located within the cell (in
cytosol or nucleus)
 Steroid hormone-receptor complex acts as
transcriptional activator to enhance
particular genes
 Transcription of gene enhance and more
of that gene’s product produced
 Can influence a number of genes within a
single cell or in different cells

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Hormones and Receptors Evolved as
Tightly Integrated Molecular Systems
 Tightly integrated molecular systems
All hormones act by binding to a receptor
Without a receptor, a hormone has no function, and
without a ligand, a receptor has no function
 Aldosterone and cortisol receptors arose 450 mya
by duplication of an ancient cortisol receptor (CR)
gene
 Deduced ancient CR sequence and synthesized it
 Both aldosterone and cortisol bound to CR with
aldosterone binding better
 Appears aldosterone receptor evolved first, and
aldosterone later
Hormone synthesis


Blood concentration of hormone increases
dramatically by changing rate of hormone
synthesis
Protein and peptide hormones synthesized at a
steady rate in an unstimulated cell
 Changing
transcription rates increases or decreases
the supply
 Reservoir of stored hormone in secretory vesicles

Steroid hormones are made on demand with no
significant storage
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Hormone removal or deactivation





Hormone concentration in blood can drop by
changing the rate of removal or deactivation
Hormones binding to plasma membrane
receptors may be engulfed by endocytosis and
degraded
May be excreted in urine
Liver may modify hormones to render them
inactive and more easily excreted by kidneys
Negative feedback can turn off signals for
synthesis and secretion of hormone
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Endocrine and nervous system links
Sensory stimuli detected by the nervous
system can activate the endocrine system
 Sensory cue perceived by a sensory
receptor sends electrical stimuli to different
brain areas including the hypothalamus
 Hypothalamus involved in reproduction,
bodily rhythms, appetite and metabolism,
and responses to stress

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Hypothalamus – Anterior Pituitary





Contains nuclei that secrete neurohormones or
hypothalamic releasing hormones
Secreted into capillaries leading to portal system
Portal vein extends through infundibular stalk
before forming new capillaries in anterior
pituitary
Allows for quick, efficient delivery of
neurohormones to targets in anterior pituitary
Anterior pituitary synthesizes 6 hormones
controlled by hypothalamic neurohormones
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Posterior pituitary gland

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

Blood supply not connected to hypothalamus
Does not respond to hypothalamic
neurohormones
Neurons in the hypothalamus synthesize 2
hormones that have axons that terminate in
posterior pituitary and release the hormones
Oxytocin – targets smooth muscle uterine
contractions (during birth and milk ejection)
Antidiuretic hormone (ADH) – acts on collecting
ducts in kidneys to increase aquaporin channels
resulting in decreased urine volume
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Metabolism and energy balance

Thyroid hormones regulate metabolic rate
 Thyroid
gland consists of follicles containing
colloid (thyroglobulin)
 Thyrotropin-releasing hormone (TRH)
stimulates thyroid-stimulating hormone (TSH)
which stimulates the thyroid to make thyroid
hormones
 Thyroxine (T4) – 4 iodine molecules
 Triiodothyronine (T3) – 3 iodine molecules
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
Thyroid hormones
 Stimulate
energy consumption
 Also increases heat production
 Iodine stored in case of deficiency
 Iodine-deficient goiters can result from low
iodine in the diet
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
Pancreas and adrenal gland hormones
regulate fuel levels in the blood
 Pancreas
Exocrine portion releases contents into small
intestine for digestion
 Endocrine portion produces insulin and glucagon

 Adrenal

glands
Produce glucocorticoids like cortisol
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 Pancreas
Islets
of Langerhans
 Alpha
cells make glucagon (raises blood
glucose)
 Beta cells make insulin (lowers blood
glucose)
Maintaining
normal blood glucose is vital
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
Low – glucagon acts
on liver to stimulate
glycogenolysis
(glucose production
from glycogen) and
cortisol stimulates
liver to synthesize
glucose from amino
acids and glycerol
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
High – insulin stimulates
movement of vesicles
containing glucose
transporters to move to
plasma membrane,
transporters bring
glucose into the cell
lowering blood glucose


Type 1 Diabetes mellitus
(T1DM) – immune system
has mistakenly destroyed
beta cells
Type 2 Diabetes mellitus
(T2DM) – cells of the body
become unable to respond
to insulin, obesity
associated
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Banting, Best, MacLeod, and Collip
Isolated Active Insulin for the First Time


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Had been unable to purify glucose lowering factor
due to digestive enzyme interference
1921 – Banting came up with the idea to ligate
pancreatic ducts to destroy the exocrine pancreas
and then purify the factor from the remaining
pancreatic tissue
Worked with medical student, Best, and
biochemist, Collip, in MacLeod’s lab
First successful test on human patients of purified
insulin in 1922
Nobel Prize in 1923 went to Banting and MacLeod

Leptin regulates appetite
 Released
by adipose cell in proportion to
amount of adipose tissue in the body
 Acts on hypothalamus to inhibit appetite
 Decreasing adipose tissue decreases leptin
increasing appetite
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Hormonal control of mineral balance

Regulating Ca2+ balance
 Among
the most tightly regulated ions
 Vitamin D derivative facilitates calcium
transport in small intestine
 Parathyroid hormone (PTH) made by
parathyroid glands acts on bone to stimulate
Ca2+ release
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
Regulation of Na+ and K+
 Also tightly regulated
 No large reservoirs like calcium
 Key is altering rate of reabsorption
of water,
Na+ and K+ from the urine
 Antidiuretic hormone (ADH) – increases
reabsorption of water in kidney
 Atrial natriuretic peptide (ANP) – secreted
from atria of heart to decrease sodium
reabsorption in kidney
 Aldosterone from the adrenal glands
increases sodium reabsorption in kidney
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Hormonal control of growth and
differentiation
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In vertebrates, anterior pituitary produces growth
hormone (GH)
GH acts on liver to produce insulin-like growth
factor-1 (IGF-1)
IGF-1 stimulates elongation of bones, especially
during puberty
Eventually, gonadal hormones will seal growth
plates preventing further elongation
In adults, GH serves metabolic functions in
regulating glucose and fatty acid levels in blood
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Pituitary giants result from excessive GH
during childhood and acromegaly if high
levels continue in adulthood
 Pituitary dwarfism results from insufficient
GH during childhood
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In amphibians, thyroid hormones play a
critical role in metamorphosis
 Promote resorption of tail and
development of legs
 Thyroid hormones responsible for change
in appearance of flatfish as they mature

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
Invertebrate growth
 Endocrine
system critical in larval growth and
metamorphosis
 Specialized nerve cells secrete brain hormone
periodically
 Stimulates prothoracic glands to synthesize
ecdysone
 Larva molts in response to each burst of
ecdysone
 Corpus allatum secretes juvenile hormone
which inhibits maturation of larva into pupa
 As larva ages, juvenile hormone drops until
larva progresses to pupa
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Hormonal control of reproduction

Gonads secrete sex steroids
– testes secrete androgens
(testosterone)
 Females – ovaries secrete estrogens (estradiol)
 Responsible for sex specific reproductive
behaviors, development of sex specific
phenotype, etc.
 Gonadotropins – luteinizing hormone (LH) and
follicle-stimulating hormone (FSH)
 Males
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Hormonal responses to stress

Adrenal glands
 Inner
adrenal medulla secretes amine
hormones norepinephrine and epinephrine
 Outer adrenal cortex subdivided into 3 zones
Glomerulosa – aldosterone maintains mineral
balance (mineralcorticoid)
 Fasciculata – glucocorticoids like cortisol
 Reticularis – androgens and estrogens

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
Glucocorticoids
 Catabolic
hormones promote tissue
breakdown
 Break down proteins to provide energy
 Promote gluconeogenesis in liver during
stress to raise blood glucose
 Catabolic effects on immune tissue can
depress immune system in prolonged stress
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Impact on Public Health

Endocrine disruptors
 Chemicals
derived from industrial waste that
resemble estrogen enough to bind to estrogen
receptors
 Decrease in number of functional germ cells
 Feminization of fish
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
Performance enhancers
 Androgens
can exert negative feedback on
LH and FSH causing testes to shrink
 Also linked to extreme aggression (“roid”
rage), cardiovascular disease and heart
attacks, skin problems and certain cancers
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