Chapter 18
The Endocrine System
Lecture Outline
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Chapter 18
The Endocrine System
• The nervous and endocrine systems act as a coordinated
interlocking supersystem, the neuroendocrine system.
• The endocrine system controls body activities by releasing
mediator molecules called hormones.
– hormones released into the bloodstream travel
throughout the body
– results may take hours, but last longer
• The nervous system controls body actions through nerve
impulses.
– certain parts release hormones into blood
– rest releases neurotransmitters excite or inhibit nerve,
muscle & gland cells
– results in milliseconds, brief duration of effects
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NERVOUS and ENDOCRINE SYSTEM
• The nervous system causes muscles to contract or glands
to secrete. The endocrine system affects virtually all body
tissues by altering metabolism, regulating growth and
development, and influencing reproductive processes.
• Parts of the nervous system stimulate or inhibit the release
of hormones.
• Hormones may promote or inhibit the generation of nerve
impulses.
• Table 18.1 compares the characteristics of the nervous and
endocrine systems.
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General Functions of Hormones
• Help regulate:
– extracellular fluid
– metabolism
– biological clock
– contraction of cardiac &
smooth muscle
– glandular secretion
– some immune functions
• Growth & development
• Reproduction
• Hormones have powerful effects
when present in very low
concentrations.
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Endocrine Glands Defined
• Exocrine glands
– secrete products into ducts which empty into body
cavities or body surface
– sweat, oil, mucous, & digestive glands
• Endocrine glands
– secrete products (hormones) into bloodstream
– pituitary, thyroid, parathyroid, adrenal, pineal
– other organs secrete hormones as a 2nd function
– hypothalamus, thymus, pancreas,ovaries,testes,
kidneys, stomach, liver, small intestine, skin, heart
& placenta
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Hormone Receptors
• Hormones only affect target cells with specific membrane
proteins called receptors
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Hormone Receptors
• Although hormones travel in blood throughout the body, they
affect only specific target cells.
– Target cells have specific protein or glycoprotein
receptors to which hormones bind.
• Receptors are constantly being synthesized and broken
down.
• Synthetic hormones that block the receptors for particular
naturally occurring hormones are available as drugs.
(Clinical Application)
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Regulation of Hormone Receptors
• Receptors are constantly being synthesized & broken
down
– range of 2000-100,000 receptors / target cell
• Down-regulation
– excess hormone leads to a decrease in number of
receptors
• receptors undergo endocytosis and are degraded
– decreases sensitivity of target cell to hormone
• Up-regulation
– deficiency of hormone leads to an increase in the
number of receptors
– target tissue becomes more sensitive to the hormone
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Blocking Hormone Receptors
• Synthetic drugs may block receptors for naturally
occurring hormones
– Normally, progesterone levels drop once/month
leading to menstruation. Progesterone levels are
maintained when a woman becomes pregnant.
– RU486 (mifepristone) binds to the receptors for
progesterone preventing progesterone from
sustaining the endometrium in a pregnant woman
• brings on menstrual cycle
• used to induce abortion
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Circulating and Local Hormones
• Hormones that travel in blood and act on distant target cells
are called circulating hormones or endocrines.
• Hormones that act locally without first entering the blood
stream are called local hormones.
– Those that act on neighboring cells are called paracrines.
– Those that act on the same cell that secreted them are
termed autocrines.
• Figure 18.2 compares the site of action of circulating and
local hormones.
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Circulating & Local Hormones
• Circulating
hormones
• Local hormones
– paracrines
– autocrines
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Chemical Classes of Hormones - Overview
• Table 18.2 provides a summary of the hormones.
• Lipid-soluble hormones include the steroids, thyroid
hormones, and nitric oxide, which acts as a local hormone in
several tissues.
• Water-soluble hormones include the amines; peptides,
proteins, and glycoproteins; and eicosanoids.
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Lipid-soluble Hormones
• Steroids
– lipids derived from
cholesterol on SER
– different functional groups
attached to core of structure
provide uniqueness
• Thyroid hormones
– tyrosine ring plus attached
iodines are lipid-soluble
• Nitric oxide is gas
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Water-soluble Hormones
• Amine, peptide and protein
hormones
– modified amino acids or
amino acids put together
– serotonin, melatonin,
histamine, epinephrine
– some glycoproteins
• Eicosanoids
– derived from arachidonic
acid (fatty acid)
– prostaglandins or
leukotrienes
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Hormone Transport in Blood
• Protein hormones circulate in free form in blood
• Steroid (lipid) & thyroid hormones must attach to transport
proteins synthesized by liver
– improve transport by making them water-soluble
– slow loss of hormone by filtration within kidney
– create reserve of hormone
• only 0.1% to 10% of hormone is not bound to
transport protein = free fraction
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General Mechanisms of Hormone Action
• Hormone binds to cell surface or receptor inside target cell
• Cell may then
– synthesize new molecules
– change permeability of membrane
– alter rates of reactions
• Each target cell responds to hormone differently
At liver cells---insulin stimulates glycogen synthesis
At adipocytes---insulin stimulates triglyceride synthesis
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Action of Lipid-Soluble Hormone
• Lipid-soluble hormones bind to and activate receptors within
cells.
– The activated receptors then alter gene expression which
results in the formation of new proteins.
– The new proteins alter the cells activity and result in the
physiological responses of those hormones.
• Figure 18.3 shows this mechanism of action.
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Action of Lipid-Soluble Hormones
• Hormone diffuses through
phospholipid bilayer & into cell
• Binds to receptor turning on/off
specific genes
• New mRNA is formed & directs
synthesis of new proteins
• New protein alters cell’s
activity
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Action of Water-Soluble Hormones
• Water-soluble hormones alter cell functions by activating
plasma membrane receptors, which set off a cascade of
events inside the cell.
– The water-soluble hormone that binds to the cell
membrane receptor is the first messenger.
– A second messenger is released inside the cell where
hormone stimulated response takes place.
• A typical mechanism of action of a water-soluble hormone
using cyclic AMP as the second messenger is seen in
Figure 18.4.
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Action of Water-Soluble Hormones
• The hormone binds to the membrane receptor.
• The activated receptor activates a membrane G-protein
which turns on adenylate cyclase.
• Adenylate cyclase converts ATP into cyclic AMP which
activates protein kinases.
• Protein kinases phosphorylate enzymes which catalyze
reactions that produce the physiological response.
• Since hormones that bond to plasma membrane receptors
initiate a cascade of events, they can induce their effects at
very low concentrations.
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Action of Water-Soluble Hormones
• Can not diffuse through plasma
membrane
• Hormone receptors are integral
membrane proteins
– act as first messenger
• The hormone binds to the
membrane receptor.
• The activated receptor activates a
membrane G-protein which turns on
adenylate cyclase.
• Adenylate cyclase converts ATP into
cyclic AMP which activates protein
kinases.
• Protein kinases phosphorylate
enzymes which catalyze reactions
that produce the physiological
response.
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Water-soluble Hormones
• Cyclic AMP is the 2nd
messenger
– kinases in the cytosol
speed up/slow down
physiological
responses
• Phosphodiesterase
inactivates cAMP quickly
• Cell response is turned
off unless new hormone
molecules arrive
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Second Messengers
• Some hormones exert their influence by increasing the
synthesis of cAMP
– ADH, TSH, ACTH, glucagon and epinephrine
• Some exert their influence by decreasing the level of cAMP
– growth hormone inhibiting hormone
• Other substances can act as 2nd messengers
– calcium ions
– cGMP
• A hormone may use different 2nd messengers in different
target cells
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Amplification of Hormone Effects
• Single molecule of hormone binds to receptor
• Activates 100 G-proteins
• Each activates an adenylate cyclase molecule which
then produces 1000 cAMP
• Each cAMP activates a protein kinase, which may
act upon 1000’s of substrate molecules
• One molecule of epinephrine may result in
breakdown of millions of glycogen molecules into
glucose molecules
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Cholera Toxin and G Proteins
• Toxin is deadly because it produces massive watery
diarrhea and person dies from dehydration
• Toxin of cholera bacteria causes G-protein to lock in
activated state in intestinal epithelium
• Cyclic AMP causes intestinal cells to actively transport
chloride (Na+ and water follow) into the lumen
• Person die unless ions and fluids are replaced & receive
antibiotic treatment
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Hormonal Interactions
• The responsiveness of a target cell to a hormone depends
on the hormone’s concentration, the abundance of the
target cell’s hormone receptors, and influences exerted by
other hormones.
• Three hormonal interactions are the
– permissive effect
– synergistic effect
– antagonist effect
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Hormonal Interactions
• Permissive effect
– a second hormone, strengthens the effects of the first
– thyroid strengthens epinephrine’s effect upon lipolysis
• Synergistic effect
– two hormones acting together for greater effect
– estrogen & LH are both needed for oocyte production
• Antagonistic effects
– two hormones with opposite effects
– insulin promotes glycogen formation & glucagon stimulates
glycogen breakdown
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Control of Hormone Secretion
• Regulated by signals from nervous system, chemical
changes in the blood or by other hormones
• Negative feedback control (most common)
– decrease/increase in blood level is reversed
• Positive feedback control
– the change produced by the hormone causes
more hormone to be released
• Disorders involve either hyposecretion or
hypersecretion of a hormone
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HYPOTHALAMUS AND PITUITARY GLAND
• The hypothalamus is the major integrating link between the
nervous and endocrine systems.
– Hypothalamus receives input from cortex, thalamus,
limbic system & internal organs
– Hypothalamus controls pituitary gland with 9 different
releasing & inhibiting hormones
• The hypothalamus and the pituitary gland (hypophysis)
regulate virtually all aspects of growth, development,
metabolism, and homeostasis.
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Anatomy of Pituitary Gland
• The pituitary gland is located in the sella turcica of the sphenoid
bone and is differentiated into the anterior pituitary
(adenohypophysis), the posterior pituitary (neurohypophysis),
and pars intermedia (avascular zone in between (Figures 18.5
and 18.21b).
• Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid
– Infundibulum attaches it to brain
• Anterior lobe = 75%
– develops from roof of mouth
• Posterior lobe = 25%
– ends of axons of 10,000 neurons found in hypothalamus
– neuroglial cells called pituicytes
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Anterior Pituitary Gland (Adenohypophysis)
• The blood supply to the anterior pituitary is from the superior
hypophyseal arteries.
• Hormones of the anterior pituitary and the cells that produce
the:
– Human growth hormone (hGH) is secreted by somatotrophs.
– Thyroid-stimulating hormone (TSH) is secreted by thyrotrophs.
– Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are
secreted by gonadotrophs.
– Prolactin (PRL) is secreted by lactrotrophs.
– Adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating
hormone (MSH) are secreted by corticotrophs.
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Flow of Blood to
Anterior Pituitary
• Controlling hormones enter blood
• Travel through portal veins
• Enter anterior pituitary at capillaries
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Anterior Pituitary
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Feedback
• Secretion of anterior pituitary gland hormones is regulated
by hypothalamic regulating hormones and by negative
feedback mechanisms (Figure 18.6, Table 18.3).
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Negative Feedback Systems
• Decrease in blood levels
• Receptors in
hypothalamus & thyroid
• Cells activated to secrete
more TSH or more T3 &
T4
• Blood levels increase
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Positive Feedback
• Oxytocin stimulates uterine contractions
• Uterine contractions stimulate oxytocin
release
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Human Growth Hormone and
Insulin-like Growth Factors
• Human growth hormone (hGH) is the most plentiful anterior
pituitary hormone.
• It acts indirectly on tissues by promoting the synthesis and
secretion of small protein hormones called insulin-like
growth factors (IGFs).
– IGFs stimulate general body growth and regulate various
aspects of metabolism.
– Various stimuli promote and inhibit hGH production
(Figure 18.7).
– One symptom of excess hGH is hyperglycemia. (Clinical
Application)
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Human Growth Hormone
• Produced by somatotrophs
• target cells synthesize insulinlike growth
– common target cells are liver, skeletal muscle,
cartilage and bone
– increases cell growth & cell division by increasing
their uptake of amino acids & synthesis of
proteins
– stimulate lipolysis in adipose so fatty acids used
for ATP
– retard use of glucose for ATP production so blood
glucose levels remain high enough to supply brain
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Regulation of hGH
• Low blood sugar stimulates
release of GHRH from
hypothalamus
– anterior pituitary releases more
hGH, more glycogen broken
down into glucose by liver cells
• High blood sugar stimulates
release of GHIH from
hypothalamus
– less hGH from anterior
pituitary, glycogen does not
breakdown into glucose
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Diabetogenic Effect of Human Growth Hormone
• Excess of growth hormone
– raises blood glucose concentration
– pancreas releases insulin continually
– beta-cell burnout
• Diabetogenic effect
– causes diabetes mellitis if no insulin activity can occur
eventually
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Thyroid Stimulating Hormone (TSH)
•
•
•
•
Hypothalamus regulates thyrotroph cells
Thyrotroph cells produce TSH
TSH stimulates the synthesis & secretion of T3 and T4
Metabolic rate stimulated
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Follicle Stimulating Hormone (FSH)
• Releasing hormone from
hypothalamus controls
gonadotrophs
• Gonadotrophs release
follicle stimulating hormone
• FSH functions
– initiates the formation of
follicles within the ovary
– stimulates follicle cells to
secrete estrogen
– stimulates sperm production
in testes
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Luteinizing Hormone (LH)
• Releasing hormones from hypothalamus stimulate
gonadotrophs
• Gonadotrophs produce LH
• In females, LH stimulates
– secretion of estrogen
– ovulation of 2nd oocyte from ovary
– formation of corpus luteum
– secretion of progesterone
• In males, LH stimulates the interstitial cells of the testes to
secrete testosterone.
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Prolactin (PRL)
• Prolactin (PRL), together with other
hormones, initiates and maintains milk
secretion by the mammary glands.
– Hypothalamus regulates
lactotroph cells
– Lactotrophs produce prolactin
– Under right conditions, prolactin
causes milk production
• Suckling reduces levels of
hypothalamic inhibition and prolactin
levels rise along with milk production
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Adrenocorticotrophic Hormone
• Adrenocorticotrophic hormone
(ACTH) controls the production and
secretion of hormones called
glucocorticoids by the cortex of the
adrenal gland.
– Hypothalamus releasing
hormones stimulate
corticotrophs
– Corticotrophs secrete ACTH &
MSH
– ACTH stimulates cells of the
adrenal cortex that produce
glucocorticoids
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Melanocyte-Stimulating Hormone
• Melanocyte-stimulating hormone (MSH) increases skin
pigmentation although its exact role in humans is
unknown.
– Releasing hormone from hypothalamus increases
MSH release from the anterior pituitary
– Secreted by corticotroph cells
• Function not certain in humans (increase skin
pigmentation in frogs )
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Posterior Pituitary Gland (Neurohypophysis)
• Although the posterior pituitary gland does not synthesize
hormones, it does store and release two hormones.
– Hormones made by the hypothalamus and stored in the
posterior pituitary are oxytocin (OT) and antidiuretic
hormone (ADH).
– The neural connection between the hypothalamus and
the neurohypophysis is via the hypothalamohypophyseal
tract (Figure 18.8).
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Posterior Pituitary Gland (Neurohypophysis)
• Does not synthesize
hormones
• Consists of axon terminals
of hypothalamic neurons
• Neurons release two
neurotransmitters into
capillaries
– antidiuretic hormone
– oxytocin
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Oxytocin
• Two target tissues both involved in
neuroendocrine reflexes
• During delivery
– baby’s head stretches cervix
– hormone release enhances uterine
muscle contraction
– baby & placenta are delivered
• After delivery
– Oxytocin stimulates contraction of the
uterus and ejection (let-down) of milk from
the breasts.
• Nursing a baby after delivery
stimulates oxytocin release, promoting
uterine contractions and the expulsion
of the placenta (Clinical Application).
• suckling & hearing baby’s cry
stimulates milk ejection
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Oxytocin during Labor
• Stimulation of uterus by baby
• Hormone release from posterior pituitary
• Uterine smooth muscle contracts until birth
of baby
• Baby pushed into cervix, increase
hormone release
• More muscle contraction occurs
• When baby is born, positive feedback
ceases
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ADH
• Antidiuretic hormone stimulates water reabsorption by the
kidneys and arteriolar constriction.
• The effect of ADH is to decrease urine volume and conserve
body water.
• ADH is controlled primarily by osmotic pressure of the blood
(Figure 18.9).
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Antidiuretic Hormone (ADH)
• Known as vasopressin
• Functions
– decrease urine production
– decrease sweating
– increase BP
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Regulation of ADH
• Dehydration
– ADH released
• Overhydration
– ADH inhibited
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THYROID GLAND - Overview
• The thyroid gland is located just below the larynx and has
right and left lateral lobes (Figure 18.10a).
• Histologically, the thyroid consists of the thyroid follicles
composed of follicular cells, which secrete the thyroid
hormones thyroxine (T4) and triiodothyronine (T3), and
parafollicular cells, which secrete calcitonin (CT) (Figures
18.10b and 18.13c).
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Thyroid Gland
• On each side of trachea is lobe of thyroid
• Weighs 1 oz & has rich blood supply
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Histology of Thyroid Gland
• Follicle = sac of stored
hormone (colloid) surrounded
by follicle cells that produced
– T3 & T4
• Inactive cells are short
• In between cells called
parafollicular cells
– produce calcitonin
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Photomicrograph of Thyroid Gland
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Formation, Storage, and Release of Thyroid Hormones
• Thyroid hormones are synthesized from iodine and tyrosine
within a large glycoprotein molecule called thyroglobulin
(TGB) and are transported in the blood by plasma proteins,
mostly thyroxine-binding globulin (TBG).
• The formation, storage, and release steps include
– iodide trapping,
– synthesis of thyroglobulin,
– oxidation of iodide,
– iodination of tyrosine,
– coupling of T1 and T2,
– pinocytosis and digestion of colloid,
– secretion of thyroid hormones, and transport in blood
(Figure 18.11).
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Formation of Thyroid Hormone
•
•
•
•
•
Iodide trapping by follicular cells
Synthesis of thyroglobulin (TGB)
Release of TGB into colloid
Iodination of tyrosine in colloid
Formation of T3 & T4 by combining
T1 and T2 together
• Uptake & digestion of TGB by follicle
cells
• Secretion of T3 & T4 into blood
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Actions of Hormones from
Thyroid Gland
• T3 & T4
– thyroid hormones
responsible for our
metabolic rate, synthesis
of protein, breakdown of
fats, use of glucose for
ATP production
• Calcitonin
– responsible for building of
bone & stops reabsorption
of bone (lowers blood
levels of Calcium)
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Control of T3 & T4 Secretion
• Negative feedback system
• Low blood levels of hormones
stimulate hypothalamus
• It stimulates pituitary to
release TSH
• TSH stimulates gland to raise
blood levels
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PARATHYROID GLANDS
• The parathyroid glands are embedded on the posterior
surfaces of the lateral lobes of the thyroid
– principal cells produce parathyroid hormone
– oxyphil cells … function is unknown (Figure 18.13).
• Parathyroid hormone (PTH) regulates the homeostasis of
calcium and phosphate
• increase blood calcium level
• decrease blood phosphate level
– increases the number and activity of osteoclasts
– increases the rate of Ca+2 and Mg+2 from reabsorption
from urine and inhibits the reabsorption of HPO4-2 so
more is secreted in the urine
– promotes formation of calcitriol, which increases the
absorption of Ca+2, Mg+2,and HPO4-2 from the GI tract
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Parathyroid
Glands
• 4 pea-sized glands found on back of thyroid gland
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Histology of Parathyroid Gland
• Principal cells produce
parathyroid hormone
(PTH)
• Oxyphil cell function is
unknown
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Blood Calcium
• Blood calcium level directly controls the secretion of
calcitonin and parathyroid hormone via negative feedback
loops that do not involve the pituitary gland (Figure 18.14).
• Table 18.7 summarizes the principal actions and control of
secretion of parathyroid hormone.
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Regulation of Calcium Blood Levels
• High or low blood levels of Ca+2 stimulate the release of different hormones
--- PTH or CT
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Adrenal Glands
• The adrenal glands are located superior to the kidneys (Figure
18.15)
• 3 x 3 x 1 cm in size and weighs 5 grams
• consists of an outer cortex and an inner medulla.
– Cortex produces 3 different types of hormones from 3
zones of cortex
– Medulla produces epinephrine & norepinephrine
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Adrenal Cortex
• The adrenal cortex is divided into three zones, each of
which secretes different hormones (Figure 18.15).
– The zona glomerulosa (outer zone)
• secretes mineralocorticoids.
– The zona fasciculata (middle zone)
• secretes glucocorticoids.
– The zona reticularis (inner zone)
• secretes androgens.
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Histology of
Adrenal
Gland
• Cortex
– 3 zones
• Medulla
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Structure of Adrenal Gland
• Cortex derived from mesoderm
• Medulla derived from ectoderm
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Mineralocorticoids
• 95% of hormonal activity due to aldosterone
• Functions
– increase reabsorption of Na+ with Cl- , bicarbonate and
water following it
– promotes excretion of K+ and H+
• Hypersecretion = tumor producing aldosteronism
– high blood pressure caused by retention of Na+ and
water in blood
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Regulation of
Aldosterone
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Glucocorticoids
• 95% of hormonal activity is due to cortisol
• Functions = help regulate metabolism
– increase rate of protein catabolism & lipolysis
– conversion of amino acids to glucose
– stimulate lipolysis
– provide resistance to stress by making nutrients
available for ATP production
– raise BP by vasoconstriction
– anti-inflammatory effects reduced (skin cream)
• reduce release of histamine from mast cells
• decrease capillary permeability
• depress phagocytosis
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Regulation of
Glucocorticoids
• Negative feedback
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Androgens from Zona Reticularis
• Small amount of male hormone produced
– insignificant in males
– may contribute to sex drive in females
– is converted to estrogen in postmenopausal females
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Adrenal Medulla
• Chromaffin cells receive direct innervation from
sympathetic nervous system
– develop from same tissue as postganglionic
neurons
• Produce epinephrine & norepinephrine
• Hormones are sympathomimetic
– effects mimic those of sympathetic NS
– cause fight-flight behavior
• Acetylcholine increase hormone secretion by adrenal
medulla
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PANCREATIC ISLETS
• The pancreas is a flattened organ located posterior and
slightly inferior to the stomach and can be classified as both
an endocrine and an exocrine gland (Figure 18.18).
• Histologically, it consists of pancreatic islets or islets of
Langerhans (Figure 18.19) and clusters of cells (acini)
(enzyme-producing exocrine cells).
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Anatomy of Pancreas
• Organ (5 inches) consists of head, body & tail
• Cells (99%) in acini produce digestive enzymes
• Endocrine cells in pancreatic islets produce hormones
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Cell Organization in Pancreas
• Exocrine acinar cells surround a small duct
• Endocrine cells secrete near a capillary
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Histology of the Pancreas
• 1 to 2 million pancreatic islets
• Contains 4 types of endocrine cells
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Cell Types in the Pancreatic Islets
•
•
•
•
Alpha cells (20%) produce glucagon
Beta cells (70%) produce insulin
Delta cells (5%) produce somatostatin
F cells produce pancreatic polypeptide
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Regulation
• Regulation of glucagon and
insulin secretion is via
negative feedback
mechanisms (Figure 18.19).
– Low blood glucose
stimulates release of
glucagon
– High blood glucose
stimulates secretion of
insulin
• Table 18.9 summarizes the
hormones produced by the
pancreas, their principal
actions, and control of
secretion.
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Ovaries and Testes
• Ovaries
– estrogen, progesterone, relaxin & inhibin
– regulate reproductive cycle, maintain pregnancy &
prepare mammary glands for lactation
• Testes
– produce testosterone
– regulate sperm production & 2nd sexual
characteristics
• Table 18.10 summarizes the hormones produced by the
ovaries and testes and their principal actions.
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Pineal Gland
•
•
•
•
Small gland attached to 3rd ventricle of brain
Consists of pinealocytes & neuroglia
Melatonin responsible for setting of biological clock
Jet lag & SAD treatment is bright light
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Effect of Light on Pineal Gland
• Melatonin secretion producing sleepiness occurs during
darkness due to lack of stimulation from sympathetic ganglion
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Seasonal Affective Disorder and Jet Lag
• Depression that occurs during winter months when day
length is short
• Due to overproduction of melatonin
• Therapy
– exposure to several hours per day of artificial light as
bright as sunlight
– speeds recovery from jet lag
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Thymus Gland
• Important role in maturation of T cells
• Hormones produced by gland promote the proliferation &
maturation of T cells
– thymosin
– thymic humoral factor
– thymic factor
– thymopoietin
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OTHER HORMONES and GROWTH FACTORS
• Several body tissues other than those usually classified as
endocrine glands also contain endocrine tissue and thus
secrete hormones.
• Table 18.11 summarizes these hormones and their actions.
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Eicosanoids
• Local hormones released by all body cells
• alter the production of second messengers, such as
cyclic AMP
– Leukotrienes influence WBCs & inflammation
– Prostaglandins alter:
• smooth muscle contraction, glandular secretion,
blood flow, platelet function, nerve transmission,
metabolism.
• Aspirin and related nonsteroidal anti-inflammatory
drugs (NSAIDS), such as ibuprofen and
acetaminophen, inhibit a key enzyme in
prostaglandin synthesis and are used to treat a
wide variety of inflammatory disorders.
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Nonsteroidal Anti-inflammatory Drugs
• Answer to how aspirin or ibuprofen works was
discovered in 1971
– inhibit a key enzyme in prostaglandin synthesis
without affecting the synthesis of leukotrienes
• Treat a variety of inflammatory disorders
– rheumatoid arthritis
• Usefulness of aspirin to treat fever & pain implies
prostaglandins are responsible for those symptoms
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Growth Factors
• Substances with mitogenic qualities
– cause cell growth from cell division
• Many act locally as autocrines or paracrines
• Selected list of growth factors (Table 18.12)
– epidermal growth factor (EGF),
– platelet-derived growth factor (PDGF),
– fibroblast growth factor (FGF),
– nerve growth factor (NGF),
– tumor angiogenesis factors (TAFs),
– Insulin-like growth factor (IFG),
– cytokines
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STRESS RESPONSE
• The stimuli that produce the general adaptation syndrome
are called stressors.
• Stressors include almost any disturbance: heat or cold,
surgical operations, poisons, infections, fever, and strong
emotional responses.
• Stages of the General Adaptation Syndrome
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Stress & General Adaptation Syndrome
• Stress response is set of bodily changes called general
adaptation syndrome (GAS)
• Any stimulus that produces a stress response is called a
stressor
• Stress resets the body to meet an emergency
– eustress is productive stress & helps us prepare for
certain challenges
– distress type levels of stress are harmful
• lower our resistance to infection
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General
Adaptation
Syndrome
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Alarm Reaction (Fight-or-Flight)
• The alarm reaction is initiated by nerve impulses from
the hypothalamus to the sympathetic division of the
autonomic nervous system and adrenal medulla
(Figure 18.20a).
• Dog attack
– increases circulation
– promote catabolism for energy production
– promotes ATP synthesis
– nonessential body functions are inhibited
• digestive, urinary & reproductive
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Resistance Reaction
• Initiated by hypothalamic releasing hormones (long-term
reaction to stress)
– corticotropin, growth hormone & thyrotropin releasing
hormones
• Results
– increased secretion of aldosterone acts to conserve
Na+ (increases blood pressure) and eliminate H+
– increased secretion of cortisol so protein catabolism is
increased & other sources of glucose are found
– increase thyroid hormone to increase metabolism
• Allow body to continue to fight a stressor
• Glucocorticoids are produced in high concentrations
during stress. They create many distinct physiological
effects.
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Exhaustion
• Exhaustion is caused mainly by loss of potassium,
depletion of adrenal glucocorticoids, and weakened
organs. If stress is too great, it may lead to death.
– Resources of the body have become depleted
– Resistance stage can not be maintained
– Prolonged exposure to resistance reaction
hormones
• wasting of muscle
• suppression of immune system
• ulceration of the GI tract
• failure of the pancreatic beta cells
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Stress and Disease
• Stress can lead to disease by inhibiting the immune
system
– gastritis, ulcerative colitis, irritable bowel
syndrome, peptic ulcers, hypertension, asthma,
rheumatoid arthritis, migraine headaches, anxiety,
and depression.
• people under stress are at a greater risk of developing
chronic disease or of dying prematurely
• Interleukin - 1
– link between stress and immunity
– secreted by macrophages; stimulates secretion of
ACTH
– stimulates production of immune substances
– feedback control since immune substance
suppress the formation of interleukin-1
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DEVELOPMENTAL ANATOMY OF THE
ENDOCRINE SYSTEM
• The pituitary gland originates from two different regions of
the ectoderm.
• The anterior pituitary derives from the neurohypophyseal
bud, located on the floor of the hypothalamus (Figure
18.21).
• The anterior pituitary is derived from an outgrowth of
ectoderm from the mouth called the hypophyseal (Rathke’s)
pouch.
• The thyroid gland develops as a midventral outgrowth of
endoderm, called the thyroid diverticulum, from the floor of
the pharynx at the level of the second pair of pharyngeal
pouches.
• Parathyroid glands develop from endoderm as outgrowths
from the third and fourth pharyngeal pouches.
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Development of the Endocrine System
• Thyroid develops ---floor of pharynx 2nd pouch
• Parathyroid & thymus --3 & 4 pharyngeal pouches
• Pancreas from foregut
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Development of Pituitary Gland
• Events occurring between 5 and 16 weeks of age
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DEVELOPMENTAL ANATOMY OF THE
ENDOCRINE SYSTEM
• The adrenal cortex is derived from intermediate mesoderm
from the same region that produces the gonads. The
adrenal medulla is ectodermal in origin and derives from the
neural crest, which also gives rise to sympathetic ganglion
and other nervous system structures (Figure 14.125b).
• The pancreas develops from the outgrowth of endoderm
from the part of the foregut that later becomes the
duodenum (Figure 29.12c).
• The pineal gland arises as an outgrowth between the
thalamus and colliculi from ectoderm associated with the
diencephalon (Figure 14.26).
• The thymus gland arises from endoderm of the third
pharyngeal pouch.
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Aging and the Endocrine System
• Production of human growth hormone decreases
– muscle atrophy
• Production of TSH increase with age to try and stimulate thyroid
– decrease in metabolic rate, increase in body fat & hypothyroidism
• Thymus after puberty is replaced with adipose
• Adrenal glands produce less cortisol & aldosterone
• Receptor sensitivity to glucose declines
• Ovaries no longer respond to gonadotropins
– decreased output of estrogen (osteoporosis & atherosclerosis)
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DISORDERS: HOMEOSTATIC IMBALANCES
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Diabetes Insipidus
• dysfunction of the posterior pituitary
• Hyposecretion of ADH
– excretion of large amounts of dilute urine and
subsequent dehydration and thirst
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Pituitary Gland Disorders
• Hyposecretion during childhood = pituitary dwarfism
(proportional, childlike body)
• Hypersecretion during childhood = giantism
– very tall, normal proportions
• Hypersecretion as adult = acromegaly
– growth of hands, feet, facial features & thickening of
skin
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Thyroid Gland Disorders
• Hyposecretion during infancy results in dwarfism &
retardation called cretinism
• Hypothyroidism in adult produces sensitivity to cold,
low body temp. weight gain & mental dullness
• Hyperthyroidism (Grave’s disease)
– weight loss, nervousness, tremor & exophthalmos
(edema behind eyes)
• Goiter = enlarged thyroid (dietary)
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Parathyroid Gland Disorders
• Hypoparathyroidism results in muscle tetany.
• Hyperparathyroidism produces osteitis fibrosa cystica
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Adrenal Gland Disorders - Tumor
– Pheochromocytomas, benign tumors of the adrenal
medulla, cause hypersecretion of medullary hormones
and a prolonged fight-or-flight response.
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Adrenal Gland Disorders - Cushing’s Syndrome
• Hypersecretion of glucocorticoids
• Redistribution of fat, spindly arms & legs due to muscle loss
• Wound healing is poor, bruise easily
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Adrenal Gland Disorders - Addison’s disease
• Hypersecretion of glucocorticoids
– hypoglycemia, muscle weakness, low BP, dehydration
due to decreased Na+ in blood
– mimics skin darkening effects of MSH
– potential cardiac arrest
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Pancreatic Disorders
• Diabetes Mellitus
– This is a group of disorders caused by an inability to
produce or use insulin.
• Type I diabetes or insulin-dependent diabetes mellitus
is caused by an absolute deficiency of insulin.
• Type II diabetes or insulin-independent diabetes is
caused by a down-regulation of insulin receptors.
– excessive urine production (polyuria)
– excessive thirst (polydipsia)
– excessive eating (polyphagia)
• Hyperinsulinism results when too much insulin is present
– causes hypoglycemia and possibly insulin shock
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end
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Photographs for Review
• Figure 18.22 shows photographs of individuals suffering
from various endocrine disorders.
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Adrenal Cortex - Review
• Mineralocorticoids
– Mineralocorticoids (e.g., aldosterone) increase sodium and water
reabsorption and decrease potassium reabsorption, helping to
regulate sodium and potassium levels in the body.
– Secretion is controlled by the renin-angiotensin pathway (Figure
18.16) and the blood level of potassium.
• Glucocorticoids
– Glucocorticoids (e.g., cortisol) promote breakdown of proteins,
formation of glucose, lipolysis, resistance to stress, anti-inflammatory
effects, and depression of the immune response.
– Secretion is controlled by CRH (corticotropin releasing hormone) and
ACTH (adrenocorticotropic hormone) from the anterior pituitary
(Figure 18.17).
• Androgens
– Androgens secreted by the adrenal cortex usually have minimal
effects.
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Adrenal Medulla - Review
• The adrenal medulla consists of hormone-producing cells,
called chromaffin cells, which surround large blood-filled
sinuses.
• Medullary secretions are epinephrine and norepinephrine
(NE), which produce effects similar to sympathetic
responses.
• They are released under stress by direct innervation from
the autonomic nervous system. Like the glucocorticoids of
the adrenal cortex, these hormones help the body resist
stress. However, unlike the cortical hormones, the medullary
hormones are not essential for life.
• Table 18.8 summarizes the hormones produced by the
adrenal glands, the principal actions, and control of
secretion.
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Review: Cell Types in the Pancreatic Islets
• Alpha cells secrete the hormone glucagon which increases
blood glucose levels.
• Beta cells secrete the hormone insulin which decreases
blood glucose levels.
• Delta cells secrete growth hormone inhibiting hormone or
somatostatin, which acts as a paracrine to inhibit the
secretion of insulin and glucagon.
• F-cells secrete pancreatic polypeptide, which regulates
release of pancreatic digestive enzymes.
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OVARIES AND TESTES - Review
• Ovaries are located in the pelvic cavity and produce sex
hormones (estrogens and progesterone) related to
development and maintenance of female sexual
characteristics, reproductive cycle, pregnancy, lactation, and
normal reproductive functions. The ovaries also produce
inhibin and relaxin.
• Testes lie inside the scrotum and produce sex hormones
(primarily testosterone) related to the development and
maintenance of male sexual characteristics and normal
reproductive functions. The testes also produce inhibin.
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PINEAL GLAND - Review
• The pineal gland (epiphysis cerebri) is attached to the roof
of the third ventricle, inside the brain (Figure 18.1).
• Histologically, it consists of secretory parenchymal cells
called pinealocytes, neuroglia cells, and scattered
postganglionic sympathetic fibers. The pineal secrets
melatonin in a diurnal rhythm linked to the dark-light cycle.
• Seasonal affective disorder (SAD), a type of depression that
arises during the winter months when day length is short, is
thought to be due, in part, to over-production of melatonin.
Bright light therapy, repeated doses of several hours
exposure to artificial light as bright as sunlight, may provide
relief for this disorder and for jet lag.
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THYMUS GLAND
• The thymus gland secretes several hormones related to
immunity .
• Thymosin, thymic humoral-factor, thymic factor, and
thymopoietin promote the proliferation and maturation of T
cells, a type of white blood cell involved in immunity.
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