THE ENDOCRINE SYSTEM
ENDOCRINE ORGANS
AN OVERVIEW
• Endocrine glands are ductless glands that produce
and release hormones to the surrounding tissue, and
they typically have a rich vascular (blood) and
lymphatic (lymph) drainage that receives their
hormones
• Endocrine glands may be strictly endocrine, such as
the pituitary, thyroid, parathyroid, adrenal, pineal and
thymus; or they may be organs that have hormone
production as one of many functions, such as the
pancreas (exocrine) , gonads (exocrine), hypothalamus
(neural), and others
– Adipose cells: leptin
– Cells of small intestine, stomach, kidneys, and heart
AN OVERVIEW
• Hormones: long-distance chemical signals that travel in
blood or lymph throughout the body
– Local hormones:
• Autocrines:
– Chemicals that exert their effects on the same cells that secrete them
» Example: prostaglandins released by smooth muscle cells cause
the smooth muscle cells to contract
• Paracrines:
– Also act locally but affect cell types other than those releasing the
paracrine chemicals
» Somatostatin released by one type of pancreatic cells inhibits the
release of insulin by a different type of pancreatic cells
• Study of hormones and the endocrine organs is called
endocrinology
HOMEOSTATIC IMBALANCE
• Certain tumor cells, such as those of
some cancers of the lungs or pancreas,
synthesize hormones identical to those
made in normal endocrine glands
– However, they do so in an excessive and
uncontrolled fashion
HORMONES
• Chemistry of Hormones:
– Hormones are chemical messengers released into
the blood to be transported throughout the body
– Hormones are long-distance chemical signals that
are secreted by the cells to the extracellular fluid and
regulate the metabolic functions of other cells
– Responses to hormones typically occur after a lag
period of seconds or even days
• Responses tend to be much more prolonged than those
induced by the nervous system
– Most hormones are amino acid bases, but
gonadal and adrenocortical hormones are
steroids, derived from cholesterol
HORMONES
• Hormones:
– Amino acid based
– Steroids
– Eicosanoids: local hormones that are biologically
active lipids released by nearly all cell membranes
• Leukotrienes: signaling chemicals that mediate inflammation
and some allergic reactions
• Prostaglandins: have multiple targets and effects, ranging
from raising blood pressure and increasing the expulsive
uterine contractions of birth to enhancing blood clotting, pain,
and inflammation
HORMONES
• Mechanisms of Hormone Action:
– Even though all major hormones circulate to virtually all tissues,
a given hormone influences the activity of only certain tissue
cells, referred to as its target cells
– Hormones bring about their characteristic effects on target
cells by altering cell activity; that is, they increase or
decrease the rates of normal cellular processes
• Precise response depends on the target cell
– Hormones typically produce:
• Changes in membrane permeability or potential , or both, by
opening or closing ion channels
• Stimulate synthesis of proteins or regulatory molecules such as
enzymes within the cell
• Activate or deactivate enzymes
• Induce secretory activity
• Stimulate mitosis
HORMONES
• Mechanisms of Hormone Action:
– Nearly all amino acid-based hormones exert their
effects through an intracellular second
messenger (G protein that is activated when a
hormone binds to a membrane receptor)
– Steroid hormones are lipid soluble and diffuse
into the cell, where they bind to intracellular
receptors, migrate to the nucleus, and activate
specific target sequences of DNA
• Involves direct gene activation by the hormone
Amino Acid-Based Hormones
and
Second-messenger Systems
• Because proteins and peptides cannot
penetrate the plasma membranes of
tissue cells, virtually all amino acidbased hormones exert their signaling
effects through intracellular second
messenger generated when a hormone
binds to a receptor on the plasma
membrane
– Cyclic AMP is the best understood today
Cyclic AMP Signaling Mechanism
• Three plasma
membrane components
interact to determine
intracellular levels of
cyclic AMP (cAMP):
– Hormone receptor
– Signal transducer (G
protein)
– Effector enzyme (adenylate
cyclase)
Cyclic AMP Signaling Mechanism
• 1. Hormone, acting as the
first messenger, binds to its
receptor:
– Receptor changes shape and
binds with a nearby inactive G
protein
• 2. G protein is activated
– Guanosine diphosphate
(GDP) bound to it is displaced
by the high-energy compound
guanosine triphosphate (GTP)
– G protein behaves like a light
switch
• It is “off” when GDP is bound
to it
• It is “on” when GTP is bound
to it
Cyclic AMP Signaling Mechanism
• 3. The activated G protein
(moving along the
membrane) binds to and
activates the effector
enzyme adenylate cyclase
– At this point the GTP bound to
the G protein is hydrolyzed to
GDP and the G protein
becomes inactive once again
• 4. The activated adenylate
cyclase generates the
second-messenger cAMP
from ATP
Cyclic AMP Signaling Mechanism
• 5. cAMP, which is free to
diffuse throughout the cell,
triggers a cascade of
chemical reactions in which
one or more enzymes
(protein kinases) are
activated
– The protein kinases
phosphorylate (add a
phosphate group to) various
proteins, many of which are
other proteins
– Because phosphorylation
activates some of these
proteins and inhibits others, a
variety of reactions may occur
in the same target cell at the
same time
Cyclic AMP Signaling Mechanism
• This type of intracellular enzymatic cascade
has a huge amplification effect. Each
activated adenylate cyclase generates large
numbers of cAMP molecules, and a single
kinase enzyme can catalyze hundreds of
reactions. Hence, as the reaction cascades
through one enzyme intermediate after
another, the number of product molecules
increases dramatically at each step.
Theoretically receptor binding of a single
hormone molecule could generate millions of
final product molecules
Cyclic AMP Signaling Mechanism
• The sequnce of reactions set into
motion by cAMP depends on the:
– Type of target cell (e.g thyroid, bone)
– The specific protein kinases it contains
– The hormone acting as first messenger (e.g.
thyroid stimulating hormone, growth hormone)
Cyclic AMP Signaling Mechanism
• Notice that on the right
side of this diagram
that some G proteins
inhibit rather than
activate adenylate
cyclase, thus reducing
the cytoplasmic
concentration of cAMP
• Such opposing effects
permit even slight
changes in levels of
antagonistic hormones
to influence a target
cell’s activity
Cyclic AMP Signaling Mechanism
• Because cAMP is rapidly degraded by the
intracellular enzyme phosphodieterase, its
action persists only briefly. This might seem a
problem but because of the amplification effect,
most hormones need to be present only briefly
to cause the desired results.
– Continued production of hormones then prompts
continued cellular activity
– No extracellular controls are necessary to stop the
activity (self-limiting)
Second-Messenger Mechanisms
of
Amino Acid-Based Hormones
Second-Messenger Mechanisms
of
Amino Acid-Based Hormones
• PIP-Calcium Signal Mechanism
– Although cyclic AMP is the activating second
messenger in some tissues for at least 10
amino acid-based hormones, some of the
same hormones (.g., epinephrine) act through
a different second-messenger system in other
tissues
– One such mechanism, called the PIPcalcium signal mechanism, intracellular
calcium ions act as the final mediator
PIP-Calcium Signal Mechanism
• 1. Hormone docking on the
receptor causes it to bind
the nearby inactive G protein
• 2. The protein is activated as
GTP binds, displacing GDP
• 3. The activated G protein
then binds to and activates
membrane-bound
phospholipase (the effector
enzyme)
– The G protein then becomes
inactive
PIP-Calcium Signal Mechanism
• 4. Phospholipase splits a
plasma-membrane
phospholipid called PIP2
(phosphatidyl inositol
biphosphate) into
diacylglycerol (DAG) and
inositol triphosphate (IP3), and
both these molecules act as
second messangers
• 5. DAG activates specific
protein kinases, and IP3
triggers the release of Ca2+
from the endoplasmic
reticulum and other
intracellular storage sites
PIP-Calcium Signal Mechanism
• 6. The liberated Ca2+
takes on a second
messenger role, either
by directly altering the
activity of specific
enzymes and plasma
membrane Ca2+ channels
or by binding to the
intracellular regulatory
protein calmodulin
– Once Ca2+ binds to
calmodulin, enzymes are
activated that amplify the
cellular response
Second-Messenger Mechanisms
of
Amino Acid-Based Hormones
• Other hormones (not listed in the previous
two diagrams) act on their target cells
through different mechanisms
– Some unknown
– Insulin and other growth factors appear to work
without second messengers
• Insulin receptor is a tyrosine kinase enzyme that is activated
by autophosphorylation (addition of phosphate to several of
its own tyrosines) when insulin binds
STEROID HORMONES
and
DIRECT GENE ACTIVATION
•
•
•
Being lipid soluble, steroid
hormones (and, strangely,
thyroid hormone, a small
iodinated amine) can diffuse
into their target cells
Once inside, they bind to an
intracellular receptor that is
activated by the coupling
The activated hormone-receptor
complex then makes its way to
the nuclear chromatin, where
the hormone binds to a DNA
associated receptor protein
specific for it
– Exception: thyroid hormone
receptors are always bound to
DNA even in the absence of
thyroid hormone
STEROID HORMONES
and
DIRECT GENE ACTIVATION
• The interaction between
DNA and hormonereceptor complex
“turns on” a gene
– Prompts transcription of
DNA to produce a
messenger RNA (mRNA)
• mRNA is then
translated on the
cytoplasmic ribosomes,
producing specific protein
molecules (enzymes)
Direct Gene Activation Mechanism
of Steroid Hormones
HORMONES
• Target Cell Specificity
– Cells must have specific membrane or
intracellular receptors to which hormones can
bind
– Target cell response depends on three factors:
• Blood levels of the hormone
• Relative numbers of target cell receptors
• Affinity (strength) of the receptor for the hormone
– Target cells can change their sensitivity to a
hormone by changing the number of receptors
HORMONES
• Target Cell Specificity
– Up-regulation: phenomenon in which target cells
form more receptors in response to rising blood levels
of the specific hormones to which they respond
– Down-regulation: phenomenon in which prolonged
exposure to high hormone concentrations
desensitizes the target cells, so that they respond
less vigorously to hormonal stimulation
• Involves loss of receptors
• Prevents the target cells from overreacting to persistently
high hormone levels
HORMONES
• Hormones influence the number and
affinity not only of their own receptors
but also of receptors that respond to
other hormones
– Example:
• Progesterone induces a loss of estrogen receptors
in the uterus, thus antagonizing estrogen’s actions
• However, estrogen causes the same cells to
produce more progesterone receptors, enhancing
their ability to respond to progesterone
HORMONES
• Potent chemicals, and they exert profound effects on
their target organs at very low concentrations
• Circulate in the blood in two forms:
– Free: most circulate unencumbered
– Bound to a protein carrier
• In general, lipid-soluble hormones (steroids and thyroid hormones)
travel in the bloodstream attached to plasma proteins
• The concentration of a hormone reflects its:
– Rate of release
– Rate of inactivation and removal from the body
• Most are removed from the blood by the kidneys or liver, and their
breakdown products are excreted from the body in urine or feces
HALF-LIFE
• Length of time a hormone remains in the
blood
• Duration of time a hormone remains in the
blood
– Usually brief
• Fraction of a minute to 30 minutes
• Shortest for water-soluble hormones
ONSET
• Time required for hormone effects to appear
varies greatly
• Some hormones provoke target organ
responses almost immediately, while others,
particularly the steroid hormones, require
hours to days before their effects are seen
• Some hormones are secreted in a relatively
inactive form and must be activated in the
target cells
DURATION
• Duration of hormone action varies from
seconds to several hours, depending on
the hormone
• Because of these variations, hormonal
blood levels must be precisely and
individually controlled to meet the
continuously changing needs of the body
Interaction of Hormones at Target Cells
• Understanding hormonal effects is a bit
more complicated than you might
expect because multiple hormones may
act on the same target cells at the
same time and in many cases the
results of such an interaction is not
predictable even when you know the
effects of the individual hormones
Interaction of Hormones at Target Cells
Types of Hormone Interaction
•
Permissiveness occurs when one hormone cannot exert its full effect
without another hormone being present
– Example: Thyroid hormone is necessary for normal timely development of
reproductive structure by reproductive hormones. Without thyroid hormone,
reproductive system development is delayed
•
Synergism occurs when more than one hormone produces the same
effects in a target cell, and their combined effects are amplified
– Example: Glucagon (pancreas) and epinephrine (adrenal medulla) cause the
liver to release glucose to the blood. When they act together, the amount of
glucose released is about 150% of what is released when each hormone acts
alone.
•
Antagonism occurs when one hormone opposes the action of another
hormone
– Example: Insulin, which lowers blood sugar levels, is antagonized by the action
of glucagon, which acts to raise blood sugar levels
– May compete for the same receptors
– May act through different metabolic pathways
– May cause down-regulation of the receptors for the antagonistic hormone
HORMONES
• Control of Hormone Release
– Most hormone synthesis and release is
regulated through negative feedback
mechanisms
• Endocrine gland stimuli may be:
– Humoral
– Neural
– Hormonal
Three Different Mechanisms of
Endocrine Gland Stimuli
HUMORAL STIMULI
•
•
•
Term humoral refers back to the
ancient use of the term humor
(viscous body fluids: blood, bile,
etc.)
Simplest of the endocrine
control systems
Endocrine glands that secrete
their hormones in direct
response to changing blood
levels of certain ions and
nutrients
– These stimuli are called
humoral stimuli to distinguish
them from hormonal stimuli,
which are also blood-borne
chemicals
– Examples:
• Parathyroid: Ca2+
• Pancreas: glucose
• Adrenal cortex: K, Cl-,HCO3-
NEURAL STIMULI
• In a few cases,
nerve fibers
stimulate hormone
release
– Example:
• Sympathetic nervous
system stimulation of
the adrenal medulla to
release catecholamines
(norepinephrine and
epinephrine) during
periods of stress
HORMONAL STIMULI
•
Many endocrine glands release
their hormones in response to
hormones produced by other
endocrine organs, and the
stimuli in these cases are called
hormonal stimuli
– Example:
• Release of most anterior pituitary
hormones is regulated by the
releasing and inhibiting hormones
produced by the hypothalamus
• Many anterior pituitary hormones
stimulate other endrocine glands
to release their hormones
•
The hypothalamus-pituitarytarget endocrine organ
feedback loop lies at the very
core of endocrinology
NEURAL SYSTEM MODULATION
– Both “turn on” factors (humoral, neural, and hormonal
stimuli) and “turn off” factors (feedback inhibition and
others) may be modified by the nervous system
• Endocrine system is NOT strictly like a thermostat
• The endocrine system can make fine adjustments
– Example: if someone in the house is cold, the thermostat will not adjust
itself
• The nervous system can, in certain cases, override normal
endocrine controls as needed to maintain homeostasis
– Allows hormone secretion to be modified by the nervous
stimulation in response to changing body needs
• Example:
– The action of insulin and several other hormones normally keeps blood
sugar levels in the range of 90-110 mg glucose per 100 ml of blood
– Under stress, blood sugar levels rise because the hypothalamus and
sympathetic nervous system centers are strongly activated ensuring
that the body has sufficient fuel for vigorous activity
ENDOCRINE ORGANS
PITUITARY GLAND
(HYPOPHYSIS)
• Size an shape of a
pea (pea on a stalk)
– The stalk, funnelshaped infundibulum,
connects the gland to
the hypothalamus
superiorly
PITUITARY GLAND
(HYPOPHYSIS)
• Two major lobes
(well-defined part of
an organ separated
by boundaries):
– One is glandular
tissue (anterior
pituitary)
– One is neural tissue
(posterior pituitary)
Pituitary-Hypothalamic Relationship
• The contrasting histology of the two pituitary lobes
reflects the dual origin of this organ
– Posterior Lobe (neurohypophysis) actually is derive from a
downgrowth of the hypothalamus and maintains its neural
connection to the brain
• Neurosecretory cells in the hypothalamus synthesize two
neurohormones and transport them along their axons to the
posterior pituitary storing them in capillary beds for distribution
throughout the body
– Anterior Lobe (glandular)(adenohypophysis) originates from
a superior outpocketing of the oral mucosa and is formed
from epithelial tissue
• Releasing and inhibiting hormones (amino acid based) secreted by
neurons in the ventral hypothalamus circulate to the
adenohypophysis, where they regulate secretion of its hormones
– No direct neural connection between the two, but there is
vascular connection
ANTERIOR PITUITARY
•
The Pituitary Gland (Hypophysis)
– The pituitary gland is connected to the hypothalamus via a stalk, the infundibulum, and
consists of two lobes: the anterior pituitary, or adenohypophysis, and the posterior pituitary,
or neurohypophysis
– Anterior Pituitary: There are six adenohypophyseal hormones (all protein) and one
prohormone
• Growth hormone (GH) stimulates body cells to increase in size and divide
• Thyroid stimulating hormone (TSH) is a tropic hormone that stimulates normal
development and secretion of the thyroid gland
• Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex to release
corticosteroid hormones
• Follicle-stimulating hormone (FSH) stimulates gamete production
• Leutinizing hormone (LH) promotes ovulation in females and production of gonadal
hormones
• Prolactin stimulates milk production in females, and may enhance testosterone in
males
• Pro-opiomelanocortin (POMC) is a prohormone that is the source of
adrenocorticotropic hormone and two opiates (pain killing neurotransmitters)(enkephalin
and beta endorphin which reduce our perception of pain under certain stressful
conditions)
– Enkephalin activity increases dramatically in pregnant women in labor
– Endorphin release is enhanced when an athlete gets a so-called second wind
and is probably responsible for the “runner’s high”
ADENOHYPOPHYSEAL
HORMONES
•
•
•
•
When the adenohypophysis (anterior pituitary) receives an appropriate chemical
stimulus from the hypothalamus, one or more of its hormone are released by certain
cells.
Although many different hormones pass from the hypothalamus to the anterior lobe,
each target cell in the anterior lobe distinguishes the message directed to it and
responds in kind—secreting the proper hormone in response to specific releasing
hormones, and shutting off hormone release in response to specific inhibiting
hormones
The hypothalamic releasing hormones are far more important as regulatory factors
because only very little hormone is stored by secretory cells of the anterior lobe
4 of the 6 are tropins (tropic hormones) which regulate the secretory action of
other endocrine glands:
–
–
–
–
•
Thyroid-stimulating hormone
Follicle-stimulating hormone
Adrenocorticotropic hormone
Luteinizing hormone
All 6 hormones affect their target cells via a cyclic AMP second-messenger
system
GROWTH HORMONES
(GH)
•
•
•
•
•
•
•
Produced by the somatotropic cells of the anterior lobe
Stimulates most body cells to increase in size and divide
Major targets are the bones and skeletal muscles
Essentially an anabolic (tissue building) hormone
Promotes protein synthesis
Encourages the use of fats for fuel, thus conserving glucose
Most growth-promoting effects of GH are mediated indirectly by
insulin-like growth factors (IGFs)(somatomedins)
– Family of growth-promoting proteins produced by the liver, skeletal
muscle, bone, and other tissues
• Stimulate uptake of amino acids from the blood and their incorporation into
cellular proteins throughout the body
• Stimulate uptake of sulfur into cartilage matrix
GROWTH HORMONES
(GH)
• Mobilizes fats from fat depots for transport to cells,
increasing blood levels of fatty acids
• Decreases the rate of glucose uptake and
metabolism:
– Because these actions antagonize those of the pancreatic
hormone insulin, they are referred to as anti-insulin actions
• In the liver, it encourages glycogen breakdown and
release of glucose to the blood
– The elevation in blood sugar levels that occurs as a result of this
glucose sparing is called the diabetogenic effect of GH,
because it mimics the high blood sugar levels typical of diabetes
mellitus
GROWTH HORMONES
(GH)
• Secretion is regulated
chiefly by two hypothalamic
hormones with antagonistic
effects
– Growth hormone-releasing
hormone (GHRH) stimulates
GH release
– Growth hormone-inhibiting
hormone (GHIH), also called
somatostatin, inhibits GH
• GHIH release is
(presumably) triggered by
the feedback of GH and IGFs
– Rising levels of GH also feed
back to inhibit its own release
GROWTH HORMONES
(GH)
• A number of secondary
triggers also influence GH
release
• GH secretion has a daily
cycle, with the highest
levels occurring during
evening sleep, but the
total amount secreted
daily peaks during
adolescence and then
declines with age
GROWTH HORMONES
HOMEOSTATIC IMBALANCE
of
GH
• Hypersecretion: excessive amounts of GH secreted
– Gigantism
• Still-active epiphyseal (growth) plates are targeted
– Acromegaly
• After the epiphyseal (growth) plates close
• Enlarged extremities
– Overgrowth of bony areas still responsive to GH (hands, feet, and face)
• Hyposecretion: low or no secretion of GH
– In adults usually causes no problems
– In children results in slowed long bone growth
– Typically accompanied by other adenohypophyseal hormones
• If thyroid-stimulating hormone and gonadotropins are lacking, the individual
will be malproportioned and will fail to mature sexually
• GH is produced commercial
– Careful therapy can promote nearly normal somatic growthally by
genetic engineering
Thyroid-Stimulating Hormone
(TSH)
•
•
•
Also called thyrotropin
Tropic hormone that stimulates
normal development and
secretory activity of the thyroid
gland
TSH release from thyrotrope cells
of the anterior pituitary is triggered
by the hypothalamic peptide
thyrotropin-releasing hormone
(TRH)
– Rising blood levels of thyroid
hormones act on both the
pituitary and the hypothalamus
to inhibit TSH secretion
– The hypothalamus, in response,
releases GHIH, which reinforces
the blockage of TSH release
Adrenocorticotropic Hormone
(ACTH)
•
•
•
•
•
Also called corticotropin
Secreted by the corticotrope cells of the
adenohypophysis
Stimulates the adrenal cortex to release
corticosteroid hormones, most
importantly glucocorticoids that help the
body to resist stressors (any stimulus
that directly or indirectly causes the
hypothalamus to initiate stress-reducing
responses, such as the fight-or-flight
response)
Release elicited by hypothalamic
corticotropin-releasing hormone (CRH)
– Has a daily rhythm, with levels
peaking in the morning, shortly after
sunrise
– Rising levels of glucocorticoids feed
back and block secretion of CRH and
consequently ACTH release
Internal and external factors that alter the
normal ACTH rhythm by triggering CRH
release include fever, hypoglycemia, and
stressors of all types
Gonadotropins
•
•
•
Regulate the function of the gonads
(ovaries and testes)
Follicle-stimulating hormone (FSH)
– In both sexes, stimulates gamete (egg
and sperm) production
Luteinizing Hormone (LH)
– In both sexes, promotes production of
gonadal hormones
• Females:
– LH works with FSH to cause
maturation of an eggcontaining ovarian follicle
– LH then independently
triggers ovulation and
promotes synthesis and
release of ovarian hormones
• Males:
– LH stimulates the interstitial
cells of the testes to
produce the male hormone
testosterone
– Called interstitial cellstimulating hormone (ICSH)
in males
Gonadotropins
•
•
•
Virtually absent from the blood of
prepubertal boys and girls
During puberty, the gonadotrope
cells of the adenohypophysis are
activated and gonadotropin levels
begin to rise, causing the gonads
to mature
In both sexes, gonadotropin
release by the
adenohypophysis is prompted
by gonadotropin-releasing
hormone (GnRH) produced by
the hypothalamus
– Gonadal hormones, produced
in response to the
gonadotropins, feedback to
suppress FSH and LH release
Prolactin
(PRL)
• Protein hormone structurally similar to GH
• Produced by lactotropes
• Stimulates the gonads of animals other than
humans:
– In humans, stimulates milk production in breast
– In males, some evidence indicates that PRL
enhances testosterone production
• Release is controlled by the hypothalamic
releasing and inhibiting hormones
Prolactin
(PRL)
•
Prolactin-releasing hormone (PRH) causes prolactin synthesis and
release, whereas prolactin-inhibiting hormone (PIH), now known to be
the neurotransmitter dopamine (DA), prevents prolactin secretion
– In males, the influence of PIH predominates
– In females, prolactin levels rise and fall in rhythm with estrogen
blood levels
• Low estrogen levels stimulate PIH release
• High estrogen levels promote release of PRH and, thus
prolactin:
– A brief rise in prolactin levels just before the menstrual
period partially accounts for the breast swelling and
tenderness some women experience:
» But because the prolactin stimulation is so brief, the
breasts do not produce milk
» In pregnant women, prolactin blood levels rise dramatically
toward the end of pregnancy, and milk production becomes
possible
» After birth, the infant’s suckling stimulates PRH release in
the mother, encouraging continued milk production
HOMEOSTATIC IMBALANCE
• Hypersecretion of prolactin:
Hyperprolactinemia
– Most frequent abnormality of adenohypophyseal
tumors
– Inappropriate lactation
– Lack of menses (menstruation)
– Breast enlargement
– Impotence in males
• Hyposecretion:
– Not a problem in anyone except women who choose
to nurse
PITUITARY
POSTERIOR PITUITARY
• Composed largely of
nerve fibers and
supporting cells
– Largely the axons of
hypothalamus neurons
• Releases
neurohormones
(hormones secreted by
neurons) received readymade from the
hypothalamus
– Thus, this area is a
hormone-storage area and
not a true endocrine gland
POSTERIOR PITUITARY
•
•
Two neurohormones are
synthesized by the hypothalamus
and secreted by the posterior
pituitary
Antidiuretic hormone (ADH) and
oxytocin are each composed of 9
amino acids (almost identical)
– Differ in only 2 amino acids, yet
have dramatically different
physiological effects
– Oxytocin acts on the smooth
muscle of the uterus and breast to
cause uterine contractions during
childbirth and milk let-down during
nursing
– Antidiuretic hormone (ADH)
acts on kidney tubules to promote
increased water reabsorption
(water balance)
– Both hormones use the PIPcalcium second-messenger
mechanism
OXYTOCIN
• Strong stimulant of uterine contraction
• Released in significantly higher amounts during
childbirth and in nursing women
• Stretching of the uterus and cervix as birth nears
dispatches afferent impulses to the
hypothalamus, which responds by synthesizing
oxytocin and triggering its release from the
neurohypophysis (posterior pituitary)
– As blood levels rise, the expulsive contraction of
labor gain momentum and finally end in birth
OXYTOCIN
• Positive feedback mechanism:
– Acts as a hormonal trigger for milk ejection in women
whose breast are producing milk in response to
prolactin
– Suckling causes a reflex-initiated release of oxytocin,
which targets specialized myoepithelial cells
surrounding the milk-producing glands. As these cells
contract, milk is forced from the breast into the infant’s
mouth
• Natural and synthetic oxytocin drugs used to
induce labor
OXYTOCIN
• Until recently, oxytocin’s role in males and
nonpregnant, nonlactating females was
unknown, but new studies reveal that this
potent peptide plays a role in sexual arousal
and orgasm when the body is already primed
for reproduction by sex hormones.
• Then, it is responsible for the feeling of sexual
satisfaction that results from that interaction
• In nonsexual relationships, it is thought to
promote nurturing and affectionate behavior,
that is, it acts as a “cuddle hormone”
PITUITARY GLAND
ANTIDIURETIC HORMONE
(ADH)
• Prevents wide swings in water balance, helping the body avoid
dehydration and water overload
• Diuresis is urine production:
– An antidiuretic is a substance that inhibits or prevents urine formation
• Hypothalamic neurons, called osmoreceptors, continually
monitor the solute concentration (and thus the water
concentration) of the blood
– When solutes threaten to become too concentrated (as might follow
excessive perspiration or inadequate fluid intake), the osmoreceptors
transmit excitatory impulses to the hypothalamus neurons, which
synthesize and release ADH
• Liberated into the blood by the neurohypophysis, ADH targets the kidney
tubules
• Tubule cells respond by reabsorbing more water from the forming urine and
returning it to the bloodstream
• Less urine is produced and blood volume increases
– As the solute concentration of the blood declines, the osmoreceptors
stop depolarization, effectively ending ADH release
ANTIDIURETIC HORMONE
(ADH)
• Other stimuli triggering ADH release:
– Pain
– Low blood pressure
– Nicotine
– Morphine
– Barbiturates
• Other stimuli inhibiting ADH
– Alcohol
– Excess water
HOMEOSTATIC IMBALANCE
• ADH deficiency:
– Diabetes insipidus
• Production of large amounts of urine and intense
thrist
• Diabetes (overflow) / insipidus (tasteless)
• Diabetes (overflow) / mellitus (honey)
– Blood sugar lost in urine
THYROID
• Butterfly-shaped
• Located in the anterior neck,
on the trachea just inferior to
the larynx
• Its two lobes are connected by
a median tissue mass called
the isthmus
• Largest pure endocrine
gland in the body
• Its prodigious (enormous)
blood supply makes thyroid
surgery a painstaking
endeavor
THYROID
•
•
•
•
The thyroid gland consists of hollow
spherical follicles
The walls of each follicle contain large
epithelial cells called follicle cells that
produce the glycoprotein thyroglobulin
The central cavity (lumen) of the
follicle stores colloid sticky material
consisting of thyroglobulin molecules
with attached iodine atoms
– Thyroid hormone is derived
from this iodinated
thyroglobulin
The parafollicular cells
– Lie in the follicular epithelium but
protrude into the soft connective
tissue that separates and
surrounds the thyroid follicles
– Produce calcitonin hormone
THYROID HORMONE
TH
• Body’s major metabolic
hormone
• Thyroid hormone consists of
two amine hormones:
– They act on all body cells to
increase basal metabolic rate
and body heat production
– Both are constructed from two
linked tyrosine amino acids
– The principal difference is that
T4 has four bound iodine
atoms, and T3 has three
• Thyroxine (T4)
– Major hormone secreted by
the thyroid follicles
• Triiodothyronine (T3)
– Most id formed at the target
tissue by conversion of T4 to
T3
THYROID HORMONE
TH
• Except for the adult
brain, spleen, testes,
uterus, and the thyroid
gland itself, TH affects
virtually every cell in
the body
• By stimulating enzymes
concerned with glucose
oxidation, it increases
basal metabolic rate
and body heat
production
– Calorigenic effect
THYROID HORMONE
TH
• Because TH provokes an increase in the
number of adrenergic receptors (alpha/beta
receptors that respond to NE or epinephrine)
in blood vessels, it plays an important role in
maintaining blood pressure
• It is an important regulator of tissue growth
and development
• It is critical for normal skeletal and nervous
system development, maturation, and for
reproductive capabilities
Synthesis of Thyroid Hormone
• Begins when TSH
(thyroid stimulating
hormone) secreted by
the anterior pituitary
binds to follicle cell
receptors
Synthesis of Thyroid Hormone
• 1.Formation and
storage of
thyroglobulin:
– After being synthesized on
the ribosomes,
thyroglobulin is transported
to the Golgi apparatus,
where sugar residues are
attached and the molecules
are packed into vesicles
– These transport vesicles
move to the apex of the
follicle cell, where their
contents are discharged
into the follicle lumen and
become part of the stored
colloid
Synthesis of Thyroid Hormone
• 2. Iodide trapping and
oxidation to iodine
– To produce the functional
iodinated hormones, the
following cells must
accumulate iodides (anions
of iodine I-) from the blood
– Because the intracellular
concentration of I- is over
30 times higher than that in
blood, iodide trapping
depends on active
transport
– Once they enter the follicle
cell, iodides are oxidized
(loss electrons) and
converted to iodine I2
Synthesis of Thyroid Hormone
• 3. Iodination:
– Once formed, iodine is
attached to tyrosine
amino acids that form
part of the
thyroglobulin colloid
– This iodination
reaction occurs at the
apical follicle cellcolloid junction and is
mediated by
peroxidase enzymes
Synthesis of Thyroid Hormone
• 4. Coupling of T2 and T1:
– Attachment of one iodine to a
tyrosine produces
monoiodotyrosine (MIT or T1)
– Attachment of two iodines
produces diiodotyrosine (DIT
or T2)
– Then, enzymes in the colloid
link T1 and T2 together
– Two linked DITs result in T4
– Linking MIT and DIT produces
T3
– At this point, the hormones are
still part of the thyroglobulin
colloid
Synthesis of Thyroid Hormone
•
5. Colloid endocytosis:
– Hormone secretion requires that
the follicle cells reclaim iodinated
thyroglobulin by endocytosis and
combine the vesicles with
lysosomes
•
6.Cleavage of the hormone for
release:
– In the lysosomes, the hormones
are cleaved out of the colloid by
lysosomal enzymes
– The hormones then diffuse from
the follicle cells into the
bloodstream
– The main hormonal product
secreted is T4
– Some T4 is converted to T3 before
secretion, but most T3 is
generated in the peripheral
tissues
THYROID HORMONES
Synthesis of Thyroid Hormone
• The initial response to TSH binding is
secretion of thyroid hormone
• Then more colloid is synthesized to
“restock” the follicle lumen
• As a general rule, TSH levels are lower
during the day, peak just before sleep,
and remain high during the night
Thyroid Hormone Transport and Regulation
• Most released T4 and T3 immediately bind to transport proteins,
most importantly thyroxine-binding globulins (TBGs) produced by
the liver
• Both T4 and T3 bind to target tissue receptors, but T3 binds
much more avidly and is about 10X more active
– Most peripheral tissues have the enzymes needed to convert T4 to T3,, a
process that entails enzymatic removal of one iodine group
• T3 seems to enter a target cell and binds to intracellular receptors
within the cell’s nucleus and initiates transcription of mRNA
• Falling T4 blood levels trigger release of thyroid-stimulating hormone
(TSH), and ultimately of more T4
• Rising T4 levels feed back to inhibit the hypothalamicadenhypophyseal axis, temporarily shutting off the stimulus for TSH
release
– At times of stress (pregnancy, prolonged cold), the hypothalamus
can secrete thyrotropin-releasing hormone (TRH), which triggers
TSH release overcoming the negative feedback controls
HOMEOSTATIC IMBALANCE
•
Hypothyroid disorders: a (left)
– Myxedema: mucous swelling
• Low metabolic rate
• Chilled
• Constipation
• Thick, dry skin puffy eyes
• Lethargy
• If due to lack of iodine a goiter develops (a)
– Follicle cells produce colloid but cannot iodinate it
HOMEOSTATIC IMBALANCE
• Hypothyroid disorders:
– Cretinism: severe hypothyroidism in infants
• Mentally retarded
• Short, disproportionately size body and a thick
tongue and neck
• Preventable if diagnosed early with iodine or
hormone supplements but once damage is done it
is irreversible
HOMEOSTATIC IMBALANCE
•
Graves’ disease: b (right)
–
–
–
–
–
–
Most common
Serum often contains abnormal antibodies that mimic TSH and continuously stimulate TH
release
Believed to be an auto-immune disease
Elevated metabolic rate; sweating; rapid, irregular heartbeat; weight loss despite adequate
food intake
Exophthalmos , protrusion of the eyeballs, may occur
Treatment: surgical removal of the thyroid gland or ingestion of radioactive iodine (131I),
which selectively destroys the most active thyroid cells
THYROID GLAND
• Calcitonin:
– Polypeptide hormone produced by the parafollicular, or C, cells of the
thyroid gland
– Targets the skeleton
– Lowers blood calcium by inhibiting osteoclast (cells that reabsorb or
break down bone matrix) activity (hence bone resorption), and
stimulates Ca2+ uptake and incorporation into the bone matrix
• Bone-sparing effect
– Excessive blood levels of Ca2+ act as a humoral stimulus for calcitonin
release, whereas declining blood Ca2+ levels inhibit calcitonin cell
secretory activity
• Calcitonin regulation of blood Ca2+ levels is short-lived but extremely rapid
– Direct antagonist of parathyroid hormone, produced by the parathyroid
glands
– Appears to be important only in childhood, when the skeleton grows
quickly
• In adults, a weak hypocalcemic ( low blood calcium) agent
THYROID GLAND
PARATHYROID GLAND
• In the posterior region of the
thyroid gland
• Usually 4 of these glands,
but can vary
– As many as 8 have been
observed, and some may be
located in other regions of the
neck
• Two major types of cells:
– Oxyphil cells:
• Function unclear
– Chief cells:
• Secrete parathyroid hormone
(PTH) , or parathormone
PARATHYROID GLAND
• Discovered by accident due to the deaths
of people whose thyroid gland was
removed
PARATHYROID GLAND
PTH
•
•
•
•
•
Parathyroid hormone
(parathormone)
Protein hormone
Single most important hormone
controlling the calcium balance
of the blood
Triggered by falling blood Ca2+
levels and inhibited by
hypercalcemia (excessive
amounts of calcium in the blood)
Increases Ca2+ levels in the blood
by stimulating three target organs:
– Skeleton (calcium salts in matrix)
– Kidneys
– intestine
PTH RELEASE
• 1. Stimulates
osteoclasts (boneresorbing cells) to
digest some of the
bony matrix and
release ionic calcium
and phosphates to
the blood
PTH RELEASE
•
•
2. Enhances reabsorption of
Ca2+ (and excretion of PO43-) by
the kidneys
3. Increases absorption of Ca2+
by the intestinal mucosal cells
– Calcium absorption by the
intestine is enhanced indirectly by
PTH’s effect on Vitamin D
activation
– Vitamin D is required for
absorption of Ca2+ from ingested
food, but the form in which it is
ingested or produced by the skin
is relatively inactive
– It must be converted by the
kidneys to its active vitamin D3
form, calcitriol (1,25dihydroxycholecalciferol), a
transformation stimulated by PTH
CALCIUM ION HOMEOSTASIS
• Essential for so many functions,
including transmission of nerve
impulses, muscle contraction, and
blood clotting, precise control of Ca2+
levels is critical
PARATHYROID HORMONES
EFFECTS
HOMEOSTATIC IMBALANCE
• Hyperparathyroidism:
– Rare and usually result of tumor
– Calcium is leached from the bones, and the bones soften
and deform as their mineral salts are replaced by fibrous
connective tissue
– Osteitis cystica fibrosa:
– Bones tend to fracture spontaneously
– Hypercalcemia: abnormally high blood Ca2+ levels
• Depression of the nervous system leading to abnormal reflexes
and weakness of the skeletal muscles
• Formation of kidney stones as excess calcium salts precipitate in
the kidney tubules
• Calcium deposits may also form in soft tissues throughout the
body and severely impair vital organ functions (metastatic
calcification)
HOMEOSTATIC IMBALANCE
• Hypoparathyroidism:
– PTH deficiency
– Results from:
• Trauma
• Thyroid surgery
• Deficiency of magnesium ( required for PTH secretion)
– Hypocalcemia (low calcium)
• Increases the excitability of neurons and accounts for the
classic symptoms of tetany such as loss of sensation, muscle
twitches, and convulsions
• Untreated: respiratory paralysis and death
ADRENAL (SUPRARENAL) GLANDS
•
•
•
The adrenal glands, or suprarenal
glands, consist of two regions:
– An inner adrenal medulla:
• More like a knot of nervous
tissue than a gland
• Part of the sympathetic
nervous system
– An outer adrenal cortex:
• Encapsulating the medullary
region
• Forms bulk of the gland
• Glandular tissue derived from
embryonic mesoderm
Perched on top of the kidneys
Each region produces its own set of
hormones, but all help us to cope with
stressful situations
ADRENAL CORTEX
•
•
Produces corticosteroids (well
over 2 dozen steroid hormones)
from three distinct regions: the
zona glomerulosa, the zona
fasciculata, and the zona
reticularis synthesized from
cholesterol
– Pathway is multistep and
involves varying intermediates
depending on the hormone
being formed
Unlike the amino acid based
hormones, steroid hormones are
not stored in cells
– Therefore, their rate of release
in response to stimulation
depends on their rate of
synthesis
ADRENAL CORTEX
• Zona glomerulosa: mainly
produces mineralocorticoids
hormones
– Hormones that help control
the balance of minerals and
water in the blood
• Zona fasciculata: produces the
metabolic hormones called
glucocorticoids
• Zona reticularis:
– Abuts the adrenal medulla
– Mainly produces small
amounts of adrenal sex
hormones (gonadocorticoids)
MINERALOCORTICOIDS
• Essential function is regulation of the
electrolyte (mineral salt) concentrations
in extracellular fluids, particularly of
Na+ and K+
– The single most abundant cation in
extracellular fluid is Na+, and although this
ion is vital to homeostasis, excessive
sodium intake and retention may promote
high blood pressure (hypertension) in
susceptible individuals
MINERALOCORTICOIDS
• Although there are several mineralocorticoids,
aldosterone is the most potent and accounts for
more than 95% of the mineralocorticoids produced
– Maintaining sodium ion balance is aldosterone’s primary job
• Performs this job by stimulating transcription of the Na+, K+-ATPase, the sodium pump that exchanges K+ for Na+
• Reduces excretion of Na+ from the body
• Primary target is the distal parts of the kidney tubules, where it
stimulates Na+ reabsorption from the forming urine and its return to
the bloodstream
• Also enhances Na+ reabsorption from perspiration, saliva, and
gastric juice
• Regulation of a number of other ions, including K+, H+, HCO3(bicarbonate), Cl- (chloride), is coupled to that of Na+; and where
Na+ goes, water follows—an event that leads to changes in blood
volume and blood pressure
– Hence, Na+ regulation is crucial to overall body homeostasis
MINERALOCORTICOIDS
• Aldosterone is also secreted by
cardiovascular organs, where it is a
paracrine (secretion of a hormone from a
source other than an endocrine gland) and
plays a completely different role in cardiac
regulation
ALDOSTERONE
• Secretion is
stimulated by rising
blood levels of K+,
low blood levels of
Na+, and decreasing
blood volume and
blood pressure
– Rising blood levels of
Na+ and lowering
blood levels of K+
inhibit aldosterone
secretion
Mechanisms Regulating Aldosterone Secretion
•
1. Renin-angiotensin
mechanism
– Major regulator
– Influences both the electrolytewater balance of the blood and
blood pressure
– Special cells of the
juxtaglomerular apparatus in the
kidneys become excited when
blood pressure (or low volume)
declines or plasma osmolarity
(solute concentration) drops
• These cells respond by releasing
renin into the blood which initiates
an enzymatic cascade leading to
the formation of angiotensin II, a
potent stimulator of aldosterone
release by the glomerulosa
– Effects are ultimately involved
in raising blood pressure
Mechanisms Regulating Aldosterone Secretion
• 2. Plasma concentration
of sodium and
potassium ions:
– Fluctuating blood
concentrations of sodium
and potassium ions directly
influence the zona
glomerulosa cells
– Increased K+ and
decreased Na+ are
stimulatory
– Decreased K+ and
increased Na+ are inhibitory
Mechanisms Regulating Aldosterone Secretion
•
3.ACTH
– Under normal circumstances,
ACTH (adrenocorticotropic
hormone) released by the anterior
pituitary has little or no effect on
aldosterone release
– However, when a person is
severely stressed, the
hypothalamus secretes more
corticotropin-releasing hormone
(CRH), and the rise in ACTH
blood levels that follows steps up
the rate of aldosterone secretion
to a small extent
– The increase in blood volume and
blood pressure that results helps
ensure adequate delivery of
nutrients and respiratory gases
during the stressful period
Mechanisms Regulating Aldosterone Secretion
•
4. Atrial natriuretic peptide (ANP)
– Hormone secreted by the heart
when blood pressure rises
– Fine tunes blood pressure and
sodium-water balance of the body
– Major effect is to inhibit the reninangiotensin mechanism
• Blocks renin and aldosterone
secretion and inhibits other
angiotensin-induced
mechanisms that enhance
water and Na+ reabsorption
• Decreases blood pressure by
allowing Na+ (and water) to
flow out of the body in urine
(natriuretic=producing salty
water)
HOMEOSTATIC IMBALANCE
• Aldosteronism:
– Hypersecretion of aldosterone
– Results from adrenal neoplasms (abnormal formation
of tissue)
– Hypertension and edema (excessive amount of fluid)
due to excessive Na+ and water retention
– Accelerated excretion of potassium ions
• If extreme, neurons become nonresponsive and muscle
weakness (eventually paralysis) occurs
• Addison’s disease:
– Hyposecretory disease of the adrenal cortex
– Involves a deficient output of both mineralocorticoids
and glucocorticoids
Adrenal Cortex
Zona Fasciculata
• Glucocorticoids:
– Essential to life
– Influences the energy
metabolism of most body
cells
– Helps to resist stressors
– Keeps blood sugar level
constant
– Maintains blood volume by
preventing the shift of
water into body tissue cells
– Hemorrhage, infections,
physical or emotional
trauma evokes a
dramatically higher output
Adrenal Cortex
Glucocorticoids
•
Types: steroid hormones
– Cortisol (hydrocortisone)
– Cortisone
– Corticosterone
•
•
•
Basic mechanism of activity on
target cells is to modify gene
activity
Regulated by negative feedback
Cortisol release is promoted by
ACTH, triggered in turn by the
hypothalamus releasing hormone
CRH (corticotropin-releasing
hormone)
– Rising cortisol levels feed back to
act on both the hypothalamus and
the anterior pituitary, preventing
CRH release and shutting off
ACTH and cortisol secretion
Adrenal Cortex
Glucocorticoids
• The normal cortisol rhythm is interrupted by acute stress of any
variety as the sympathetic nervous system overrides the (usually)
inhibitory effects of elevated cortisol levels and triggers CRH release
• The resulting increase in ACTH blood levels causes an outpouring
of cortisol from the adrenal cortex
• Stress results in a dramatic rise in blood levels of glucose, fatty
acids, and amino acids, all provoked by cortisol
–
–
–
–
Provokes gluconeogenesis: formation of glucose from fats and proteins
Encourages use of fats for energy
Stored proteins are broken down for enzyme synthesis
Enhances epinephrine’s vasoconstrictive effects raising blood pressure
and circulatory efficiency helping ensure that nutrients are quickly
distributed to cells
Adrenal Cortex
Glucocorticoids
• Cortisol excess:
– Depress cartilage and bone formation
– Inhibit inflammation by stabilizing lysosomal membranes and
preventing vasodilation
– Depress the immune system
– Promote changes in cardiovascular, neural, and gastrointestinal
function
• Drug use:
– Used to control many chronic inflammatory disorders
• Rheumatoid arthritis
• Allergic responses
– However: double-edged sword
• Although they relieve some of the symptoms of these disorders,
they also cause the undesirable effects of excessive levels of these
hormones
HOMEOSTATIC IMBALANCE
•
Cushing’s disease (syndrome):
– Excess Glucocorticoid
• Hyperglycemia (steroid diabetes):
increased blood sugar
– Dramatic losses in muscle and
bone protein
– Water and salt retention
– Hypertension and edema
– Redistribution of fat (note back of
neck)
– Because of enhanced antiinflammatory effects
• Tendency to bruise
• Poor wound healing
• Infections may become severe
before producing recognizable
symptoms
– Treatment:
• Surgical removal of tumor
• Discontinuation of drug
HOMEOSTATIC IMBALANCE
• Addison’s disease:
– Hyposecretory disorder of adrenal cortex
– Deficits in both glucocorticoids and
mineralocoticoids
– Lose weight
– Plasma glucose and sodium levels drop
– Potassium levels rise
– Severe dehydration and hypotension
Adrenal Cortex
Gonadocorticoids
• Sex hormones
• Bulk secreted by adrenal cortex
• Are mostly weak androgens (male sex hormones)
– Androstenedione
– Dehydropiandrosterone (DEHA)
• Converted to the more potent male hormone, testosterone, in
the tissue cells to estrogen (female sex hormones) in females
• Adrenal cortex also makes small amounts of female hormones
(estradiol and other estrogens)
• Amounts are insignificant compared with the amounts made by
the gonads during late puberty and adulthood
• Contribute to the onset of puberty and appearance of axillary and
pubic hair
• Female: thought to be important in sex drive
– May account for production of estrogen after menopause
HOMEOSTATIC IMBALANCE
Gonadocorticoids
• Hypersecretion:
– Androgenital syndrome: masculinization
• In adult males: no major effect since testicular
testosterone has already produced virilization
• In prepubertal males and females, the results can
be dramatic
– Male: maturation of the reproductive organs and
appearance of the secondary sex characteristics occur
rapidly, and the sex drive emerges with a vengeance
– Female: develop a beard and a masculine pattern of
body hair distribution, and the clitoris grows to resemble
a small penis
ADRENAL MEDULLA
• Part of the autonomic
nervous system
• The adrenal medulla
contains chromaffin
(modified ganglionic
cells) cells that
synthesize the
catecholamines
epinephrine and
norepinephrine via a
molecular sequence from
tyrosine to dopamine to
NE to epinephrine
ADRENAL MEDULLA
• When the body is activated
to fight-or-flight status by
some short-term stressor,
the sympathetic nervous
system is mobilized
– Blood sugar levels rise
– Blood vessels constrict
– Heart beats faster raising the
blood pressure
– Blood is diverted from
temporarily nonessential
organs to the brain, heart, and
skeletal muscles
– Preganglionic sympathetic
nerve endings signal for
release of catecholamines,
which reinforce and prolong
the fight-or-flight response
ADRENAL MEDULLA
• Unequal amounts of the two hormones are stored and
released (approximately 80 % is epinephrine and 20 %
norepinephrine)
• With a few exceptions, the two hormones exert the
same effects
– Norepinephrine: chiefly a vasoconstrictor with little effect on
cardiac output except with beta receptors (increase heart rate)
• Epinephrine is the more potent stimulator of the
heart and metabolic activities
• Norepinephrine has the greatest influence on
peripheral vasoconstriction and blood pressure
ADRENAL GLAND
ADRENAL GLAND
• Unlike the
adrenocortical
hormones, which
promote long-lasting
body responses to
stressors,
catecholamines
cause fairly brief
responses
STRESS
and
THE ADRENAL GLAND
HOMEOSTATIC IMBALANCE
ADRENAL MEDULLA
• Hyposecretion:
– Because hormones of the adrenal medulla merely intensify
activities set into motion by the sympathetic nervous system
neurons, a deficiency of these hormones is not a problem
– Adrenal catecholamines are not essential for life
• Hypersectretion:
– Produces symptoms of uncontrolled sympathetic nervous
system activity
• Hyperglycemia: increased blood sugar
• Increased metabolic rate
• Rapid heartbeat and palpitations (sensation of rapid or irregular
beating of the heart)
• Hypertension: high blood pressure
• Intense nervousness
• Sweating
PANCREAS
• Located partially behind
the stomach in the
abdomen
• The pancreas is a
mixed gland that
contains both
endocrine and exocrine
gland cells
• Exocrine function:
produces an enzyme-rich
juice that is ducted into
the small intestine during
food digestion
PANCREAS
•
•
•
Endocrine function: pancreatic
islets called the islets of
Langerhans that produce
pancreatic hormones
Islets contain two types of
hormone-producing cells:
– Alpha cells produce
glucagon
– Beta cells produce insulin
Some islet cells also synthesize
other peptides in small
amounts:
– Somatostatin
• Inhibits gastric mobility
• Blocks exocrine and
endocrine function of
pancreas
– Pancreatic polypeptide (PP)
PANCREAS
• The effects of
glucagon and
insulin are
antagonistic:
– Glucagon is
hyperglycemic
– Insulin is
hypoglycemic
GLUCAGON
– A 29-amino acid polypeptide
– Extremely potent hyperglycemic agent
• One molecule can cause the release of 100 million molecules
of glucose into the blood
– Targets the liver where it promotes:
• Breakdown of glycogen to glucose (glycogenolysis)
• Synthesis of glucose from lactic acid and from
noncarbohydrate molecules (gluconeogenesis)
• Release of glucose to the blood by liver cells, which causes
blood sugar to rise
• A secondary effect is a fall in the amino acid concentration in
the blood as the liver cells sequester these molecules to
make new glucose molecules
GLUCAGON
• Secretion by the alpha
cells is prompted by
humoral stimuli, mainly
falling blood sugar levels
• Sympathetic nervous
system stimulation and
rising amino acid levels
(after rich protein meal)
are also stimulatory
• Suppressed by rising
blood sugar levels and
somatostatin
INSULIN
• A small 51-amino acid protein consisting of
two amino acid chains linked by disulfide (-S—S--) bonds
• Synthesized as part of a larger polypeptide
chain called proinsulin
– Middle portion is excise by enzymes,
releasing functional insulin
• Occurs in the secretory vesicles just before insulin
is released from the beta cells
INSULIN
• Main effect is to lower blood
sugar levels by enhancing
membrane transport of
glucose into body cells
– Especially muscle and fat cells
– Does not accelerate glucose
entry into liver, kidney, and
brain tissue (cerebral cortex
and hippocampus are well
supplied with insulin
receptors), all of which have
easy access to blood glucose
regardless of insulin levels
• Also influences protein and
fat metabolism
INSULIN
• Inhibits the breakdown of glycogen to
glucose and the conversion of amino
acids or fats to glucose
– Counters any metabolic activity that would
increase plasma levels of glucose
INSULIN
• After glucose enters a target cell,
insulin binding triggers enzymatic
activities that:
– 1. Catalyze the oxidation of glucose for ATP
production
– 2. Join glucose molecules together to form
glycogen
– 3. Convert glucose to fat (particularly in
adipose tissue)
INSULIN
• As a rule, energy needs are met first,
followed by glycogen formation
• Finally, if excess glucose is still available, it
is converted to fat
• Insulin also stimulates amino acid uptake
and protein synthesis in muscle tissue
• Insulin sweeps glucose out of the blood,
causing it to be used for energy or converted to
other forms (glycogen or fats), and it promotes
protein synthesis and fat storage
INSULIN
• Pancreatic beta cells are
stimulated to secrete insulin
chiefly by:
– Elevated blood sugar levels
– Rising plasma levels of amino
acids and fatty acids
– Release of acetylcholine by
parasympathetic nerve fibers
– Hyperglycemic hormone
(glucagon, epinephrine,
growth hormone, thyroxine,
glucocorticoids) called into as
blood sugar levels drop
indirectly stimulates insulin
release by promoting glucose
entry into the blood-stream
PANCREAS
PANCREAS
INSULIN
• As body cells take
up sugar and other
nutrients, and
plasma levels of
these substances
drop, insulin
secretion is
suppressed
• Somatostatin
depresses insulin
release
INSULIN
• Thus, blood sugar levels represent a
balance of humoral and hormonal
influences
• Insulin and (indirectly) somatostatin are
the hypoglycemic factors that
counterbalance the many hyperglycemic
hormones
REGULATION OF BLOOD SUGAR
LEVELS
HOMEOSTATIC IMBALANCE
PANCREAS
• Diabetes mellitus (DM)
– Results from either hyposecretion or hypoactivity of insulin
– Hypoactivity:
• Insulin is absent or deficient
• Blood sugar levels remain high after a meal because glucose is
unable to enter most tissue cells
• Ordinarily , when blood sugar levels rise, hyperglycemic hormones
are not released BUT:
– When hyperglycemia becomes excessive, the person begins to feel
nauseated, which precipitates the fight-or-flight response
– This results, inappropriately, in all the reactions that normally occur in
the hypoglycemic (fasting) state to make glucose available—that is,
glycogenolysis (glycogen breakdown), lipolysis (breakdown of fat), and
gluconeogenesis (synthesis of glucose from noncarbohydrate
molecules)
– Thus, the already high blood sugar levels soar even higher, and
excesses of glucose begin to be lost from the body in the urine
(glycosuria)
HOMEOSTATIC IMBALANCE
PANCREAS
• Lipidemia (lipemia):
– When sugars cannot be used as cellular fuel, more fats are
mobilized, resulting in high fatty acid levels in the blood
– In severe cases of diabetes mellitus, blood levels of fatty acids
and their metabolites (collectively called ketones) rise
dramatically
• Ketones are organic acids (e.g.: acetone)
– When they accumulate in the blood, the blood pH drops, resulting in
ketoacidosis
– Ketones show in the urine (ketonuria)
– Life threatening
– Nervous responds by initiating rapid deep breathing to blow off CO2
from the blood and increase blood pH
– If untreated, disrupts heart activity and oxygen transport
– Severe depression of the nervous system leads to coma and death
HOMEOSTATIC IMBALANCE
PANCREAS
• Excessive glucose in the kidney filtrate acts as an osmotic
diuretic, that is, it inhibits water reabsorption by the kidney
tubules
• Result: Three cardinal sins of diabetes mellitus
– Polyuria: huge urine output that leads to decreased blood volume and
dehydration
• Serious electrolyte losses
– Ketones are negatively charged and carry positive ions out with them (Na+, K+)
– Because of the electrolyte imbalance, the person getsa abdominal pains and may
vomit, and the stress reaction spirals even higher
– Polydipsia: excessive thrist
• Hypothalamic thirst stimulated by dehydration
– Polyphagia: excessive hunger and food consumption
• Final sign
• Sign that the person is “starving in the land of plenty”
– Although plenty of glucose is available, it cannot be used, and the body starts to
utilize its fat and protein stores for energy metabolism
HOMEOSTATIC IMBALANCE
PANCREAS
•
•
Excessive glucose in the kidney filtrate acts as
an osmotic diuretic, that is, it inhibits water
reabsorption by the kidney tubules
Result: Three cardinal sins of diabetes mellitus
– Polyuria: huge urine output that leads to
decreased blood volume and dehydration
• Serious electrolyte losses
– Ketones are negatively charged
and carry positive ions out with
them (Na+, K+)
– Because of the electrolyte
imbalance, the person getsa
abdominal pains and may vomit,
and the stress reaction spirals
even higher
– Polydipsia: excessive thrist
• Hypothalamic thirst stimulated by
dehydration
– Polyphagia: excessive hunger and food
consumption
• Final sign
• Sign that the person is “starving in the
land of plenty”
– Although plenty of glucose is
available, it cannot be used,
and the body starts to utilize
its fat and protein stores for
energy metabolism
SYMPTOMATIC RESULTS OF INSULIN DEFICIT
(DIABETES MELLITUS)
Diabetes Mellitus
•
Type I:
– Insulin dependent
– Asymptomatic period during which the beta cells are systemically destroyed by
an autoimmune response
– Genes have been localized on several chromosomes
• Multigene autoimmune response
– Some investigation has indicated that in certain circumstances a virus that
mimics the beta cells invades the body
• Immune system attacks both
– Totally lack insulin
– Long term vascular and neural problems
– Insulin injections
• Artificial pancreas with pump and glucose sensor inserted into a large vein near the
heart
– Two month supply of insulin
– Computer programmed
• Transplants (immunosuppression problem)
• Today there might be insulin mist inhalers
Diabetes Mellitus
• Type II:
– 90% of known diabetes mellitus
– Non-insulin dependent
– Grows increasing common with age
– Hereditary predisposition
• 30% carry a gene that predisposes them
– Produce insulin but for some reason the
insulin receptors are unresponsive
• Membrane protein (PC-1) inhibits the insulin
receptor tyrosine kinase
Diabetes Mellitus
TYPE II
– Lifestyle factors
• Overweight
– Overproduce a hormonelike chemical called tumor necrosis factor-alpha
» depresses synthesis of a translocation protein (glut4) which enables glucose
to pass through insulin-primed plasma membranes
» Cells cannot take up glucose in its (glut4) absence
• Sedentary
• Weight loss and exercise can lower the risk of type II diabetes, even for
people at high risk
– Ketoacidosis is not a major problem
– Treatment:
• Oral medication (orinase) can be taken
– But if severe injection of insulin needed (produced by recombinant DNA)
• Drugs to increase the sensitivity of receptors
• Blood testing
–
–
–
–
Lance
Infrared beam
Electric current
ultrasound
HOMEOSTATIC IMBALANCE
• Hyperinsulinism:
– Excessive insulin secretion
– Results in hypoglycemia: low blood sugar levels
• Triggers the release of hyperglycemic hormones, which
cause anxiety, nervousness, tremors, and weakness
• Insufficient glucose delivery to the brain causes
disorientation, progressing to convulsions, unconsciousness,
and even death
– Cause:
• Tumor
• Overdose of insulin
– Treated by ingesting some sugar
GONADS
GONADS
• Produce steroid sex hormones,
identical to those produced by adrenal
cortical cells
– The major distinction is the source and
relative amounts produced
GONADS
• Female: paired ovaries are small, oval organs located in the
abdominopelvic cavity
– Produces:
• Ova (eggs)
• Hormones:
– Estrogen (most important)
» Maturation of the reproductive organs
» Appearance of secondary sex characteristics at puberty
» Acting with progesterone, promotes breast development
» Initial cyclic changes in the uterine mucosa (menstrual cycle) preparatory to
implantation of the blastocyst
– Progesterone
» Produced in the corpus luteum (endocrine structure that develops within a
ruptured ovarian follicle) and placenta
» Responsible for changes in the endometrium in the second half of the
menstrual cycle preparatory to implantation of the blastocyst
– Inhibin
» Produced in the corpus luteum
» Inhibits the secretion of gonadotropin-releasing hormone
GONADS
• Male: testes, located in an extra-abdominal
skin pouch (scrotum)
– Produces:
• Sperm
• Hormones:
– Testosterone
» Initiates the maturation of the male reproductive organs
and the appearance of secondary sex characteristics
during puberty
» Responsible for the sex drive
» Necessary for normal sperm production
» Maintains the reproductive organs in their mature
functional state in adult males
– Inhibin
» Inhibits the secretion of gonadotropin-releasing hormone
HOMEOSTATIC IMBALANCE
• Male:
– Prostatic hyperplasia:
• Inhibin levels high
– Cancer of the prostate:
• Inhibin levels low
– Testes: in addition these conditions could be related to anterior pituitary
problems
• Hyperfunction (hypergonadism)
– Early maturity such as large sexual organs with early functional activity and
increased growth of hair
• Hypofunction (hypogonadism)
–
–
–
–
–
–
Indicated by undeveloped testes
Absence of body hair
High pitched voice
Loss of sexual desire
Low metabolism
Eunuchoid (eunuch): retarded development of sex organs
HOMEOSTATIC IMBALANCE
• Female: in addition these conditions could
be related to anterior pituitary problems
• Hyperfunction (hypergonadism):
– Early maturity such as large sexual organs with early
functional activity
• Hypofunction (hypogonadism):
–
–
–
–
Indicated by undeveloped ovaries
Loss of sexual desire
Low metabolism
Eunuchoid (eunuch): retarded development of sex
organs
PINEAL GLAND
PINEAL GLAND
•
•
•
Tiny, pine cone-shaped gland
Hangs from the roof of the third ventricle in the diencephalon of the
brain
Secretory cells called pinealocytes
– Between these cells are dense particles containing calcium salts (brain sand or
pineal sand)
• These salts are radiopaque (impenetrable to X-rays or other forms of radiation)
– Hence, the pineal gland is a handy landmark for determining brain orientation in X rays
– Secrets melatonin, a hormone derived from serotonin
• Concentrations in blood rise and fall in a diurnal cycle
– Peak levels occur during the night and make us drowsy
– Lowest levels occur around noon
•
Indirectly receives input from the visual pathways in order to
determine the timing of day and night
• In some animals, mating behavior and gonadal size vary with changes in the relative
lengths of light and dark periods, and melatonin mediates these effects
• In children, melatonin may have an antigonadotropic effect, that is, it may inhibit
precocious (too early) sexual maturation and thus affect the timing of puberty
PINEAL GLAND
• Suprachiasmatic nucleus of the
hypothalamus (biological clock) is richly
supplied with melatonin receptors
– Exposure to bright light (known to suppress melatonin
secretion) can reset the clock timing
– Hence, changing melatonin levels may also be a
means by which the day/night cycles influence
physiological processes that show rhythmic
variations
• Such as body temperature, sleep, and appetite
THYMUS
THYMUS
• Located deep to the sternum in the thorax
• Large and conspicuous in infants and
children
• Diminishes in size throughout adulthood
– By old age, it is composed largely of adipose and
fibrous connective tissue
• Produces a family of peptide hormones:
– thymopoietin, thymic factor, and thymosin, which are
essential for the development of T lymphocytes and
the immune response
OTHER HORMONE-PRODUCING
STRUCTURES
• Heart: The atria of the
heart contain specialized
cardiac muscle cells that
secrete atria natriuretic
peptide
– Signals the kidneys to
increase their production of
salty urine
– Inhibits aldosterone release
by the adrenal cortex
– resulting in decreased
blood volume, blood
pressure, and blood
sodium concentration
OTHER HORMONE-PRODUCING
STRUCTURES
• Gastrointestinal tract:
– Enteroendocrine cells are hormonesecreting cells sprinkled in the mucosa of
the gastrointestinal (GI) tract
• Secrete amine and peptide hormones to regulate
digestive functions
– Many of these hormones are chemically identical to
neurotransmitters:
» They act as paracrines (secretion of a hormone
from a source other than an endocrine gland)
OTHER HORMONE-PRODUCING
STRUCTURES
• Placenta:
– Besides sustaining the fetus during pregnancy, the
placenta secretes several steroid and protein
hormones that influence the course of pregnancy
• Estrogens, progesterone, and human chorionic gonadotropin,
which act on the uterus to influence pregnancy
• Kidneys:
– The kidneys produce erythropoietin, which signals the
bone marrow to produce red blood cells
OTHER HORMONE-PRODUCING
STRUCTURES
• SKIN:
– Produces cholecalciferol, an inactive form of vitamin D3, when
modified cholesterol molecules in epidermal cells are exposed to
ultraviolet radiation
• This compound then enters the blood via the dermal capillaries, is
modified in the liver, and becomes fully activated in the kidney.
– The active form of vitamin D3, calcitriol, is an essential part of the
carrier system that intestinal cells use to absorb Ca2+ from ingested
food
– Without this vitamin, the bones become weak and soft
• Adipose tissue:
– Produces leptin, following their uptake of glucose and lipids,
which they store as fat
• Binds to CNS neurons concerned with appetite control, producing a
feeling of satiety
– Produces resistin, an insulin antagonist
DEVELOPMENTAL ASPECTS
OF
THE ENDOCRINE SYSTEM
• Endocrine glands derived from mesoderm
produce steroid hormones; those derived from
ectoderm or endoderm produce amines,
peptides, or protein hormones
• Environmental pollutants have been
demonstrated to have effects on sex hormones,
thyroid hormone, and glucocorticoids
• Old age may bring about changes in rate of
hormone secretion, breakdown, excretion, and
target cell sensitivity