Download System 2

The Human Endocrine
System
ENDOCRINE SYSTEM
Endocrine glands: glands that lack ducts (ductless),
secrete hormones directly into the blood that affect target
cells.
Exocrine glands are the ones that their secretions go via
ducts to the lumen of other organs (like salivary glands
leading to oral cavity ) or outside the body (sweat glands).
Hormones are biologically active molecules, that affect
metabolism of their target organs, help regulate total body
metabolism, growth, reprodution.
Neurohormones are secreted into blood by specialized
neurons.
Why hormones affect only the target organ?
Hormones are regulatory chemicals that work at a distance
between organs traveling through the bloodstream from the
gland to the target cell. The hormone binds only to cells
having its receptor. Signaling can also be paracrine or
autocrine.
Neural and Endocrine Regulation
• Both use chemicals to communicate
• Some are used both as hormone and neurotransmitters
(NTs).
• Differences:
• NTs diffuse across a synaptic cleft
• Hormones are transported in blood. They have more
diverse effects on their targets.
• Physiological regulation:
• Targets for both NTs and hormones must have specific
receptor proteins
• Binding must cause a specific sequence of changes in
the target cells
• Must be a mechanism to turn off the action of the
regulator. The endocrine system rely on negative
feedback mechanisms.
Hormones classes based on their chemistry
• Amines: are hormones derived from 2 amino acids
(tryptophan and tyrosine) they include hormones secreted
from:
1- Thyroid gland : T3 and T4.
2- Pineal gland : melatonine.
3- Adrenal medulla: epinephrine and norepinephrine.
• polypeptides: less than 100 aminoacids e.g ADH
• Proteins: more than 100 aminoacids e.g Growth hormones.
• Glycoproteins: consist of polypeptides with one or more
carbohydrate groups e.g: follicle stimulating hormone (FSH),
Luteinizing hormone (LH) and thyroid stimulating hormone
(TST).
• Steroids are lipids derived from cholesterol e.g
progesterone, testesterone, estradiol, cortisol, aldosterone.
Water-soluble (hydrophilic)
Lipid-soluble (hydrophobic)
Polypeptides
Steroids
0.8 nm
Insulin
Cortisol
Amines
Epinephrine
Thyroxine
Polarity of the hormones
• Polar hormones – water-soluble.
– Polypeptides, glycoproteins hormones
– Exception: melatonin derived from nonpolar amino acid
tryptophan can pass through the plasma membrane
• Nonpolar or lipophilic hormones – insoluble in water and
can pass through plasma membrane of their target cells
– Steroid hormones
– Thyroid hormones: composed of the amino acid tyrosine
with iodine atoms
• Steroid and thyroid hormones are active when taken orally
e.g contraceptive pills. Melatonine is also taken orally.
• Polypeptide and protein hormones are not given orally e.g
insulin injections.
Prohormones and Prehormones
• Prohormones – precursors molecules
– e.g. proinsulin is cut and spliced together to form insulin
• Prehormones – precursors of hormones
– e.g. preinsulin
• Some hormones are inactive until activated by target cells
• The term prehormone designates the molecules secreted by
endocrine glands but are inactive until they are changed into
active form in their target cell
• e.g. thyroxine (T4) is inactive until converted to T3 in
target cells
• Prehormone = T4 (inactive) T3 (active)
• Prehormone = Vit D3 (2 hydroxylations) 1,25 dihydroxyvit
D3 (active).
Hormone Interactions
• Target tissue usually responds to a number of different
hormones
1. Synergistic – two hormones work together
– Produce a larger effect together than the added effect
– e.g. norepinephrine and epinephrine on heart rate
-FSH and testesterone each is important in specific step in
spermatogenesis; complimentary action.
-Estrogen, cortisol, prolactin, have complimentary effect on
mammary glands to produce and secret milk.
Hormone Interactions
2. Permissive effect – one hormone enhances the
responsiveness of a target organ to a second hormone
– e.g. estradiol induces formation of receptors for
progesterone.
– Low calcium levels in blood stimulates the release of
parathyroid hormone (PTH) which has Permissive effect
on Vit. D. PTH induces Vit D hydroxylations in liver and
kidney 1,25 dihydroxy vit D increases Ca2+
reabsorbtion by intestine thereby rises Ca2+ level in the
blood.
3. Antagonistic – action of one inhibits the effect of the
other
– e.g. lactation during pregnancy (high prolactin) inhibited by
estrogen (inhibits secretion and action of prolactin).
– pancreatic islets secrete Insulin and Glucagon which has
Antagonistic effects.
Insulin
Body cells
take up more
glucose.
Blood glucose
level declines.
Beta cells of
pancreas
release insulin
into the blood.
Liver takes
up glucose
and stores it
as glycogen.
STIMULUS:
Blood glucose level rises
(for instance, after eating a
carbohydrate-rich meal).
Homeostasis:
Blood glucose level
(70–110 mg/m100mL)
STIMULUS:
Blood glucose level
falls (for instance, after
skipping a meal).
Blood glucose
level rises.
Liver breaks
down glycogen
and releases
glucose into
the blood.
Alpha cells of pancreas
release glucagon into
the blood.
Glucagon
Hormone Levels and Tissue Responses
• Half-life – time required for plasma concentration of a
hormone to be reduced by half
– Ranges from minutes to hours for most (days for thyroid
hormones)
• Normal tissue responses produced only when hormones are
within normal physiological range
• High (pharmacological) doses – cause side effects
– Probably by binding to receptors of different but closely
related hormones
Hormone Levels and Tissue Responses
• Priming effect (upregulation)
– a hormone induces more of its own receptors in target
cells
– Results in greater response in target cell
– e.g. GnRH secreted by the hypothalamus increases
sensitivity of anterior pituitary cells to further stimulation
(upregulation of receptors)
• Desensitization (downregulation)
– occurs after long exposure to high levels of polypeptide
hormone (e.g. adipose cells to insulin)
– Subsequent exposure to this hormone produces a lesser
response (downregulation of receptors)
– Most peptide hormones have pulsatile secretion
(spurts) which prevents downregulation
Mechanisms of Hormone Action
• Target cell receptors show
– specificity, high affinity (strength of binding), and low capacity
(saturation) for a hormone
• Lipophilic hormones
– have receptors in target's cytoplasm and/or nucleus
– diffuse through plasma membrane
– target is the nucleus where they affect transcription
• Called genomic action and takes at least 30 minutes
• Receptors for hydrophilic hormones
– are on surface of target cell
– These act through 2nd messengers; effects are quick
– Some steroids also act on cell surface receptors
• Called nongenomic action
Mechanism of Steroid Hormones
• Lipid hormones travel in blood
attached to carrier proteins
– dissociate from carriers
– pass through plasma
membrane to target cell
• Bind to receptors in the cytoplasm
– nuclear hormone receptor
• Hormone-receptor complex
translocates to nucleus binds DNA
• Genetic transcription and
translation produce proteins
Nuclear Hormone Receptors
• Serve as transcription
factors when bound to
hormone ligands to activate
transcription
• “Superfamily" – steroid family
and thyroid hormone family
– Also Vitamin D and
retinoic acid
Hormones That Use Second Messengers
• Water soluble hormones use cell surface receptors
• Actions are mediated by 2nd messengers
– Hormone is the extracellular signal
– 2nd messenger carries signal from receptor to inside of cell
• Adenylate Cyclase-cAMP 2nd Messenger System
• cAMP mediates effects of many polypeptide and glycoprotein
hormones
• Hormone binds to receptor causing dissociation of a G-protein
subunit that binds to and activates adenylate cyclase
• Inhibitory subunit dissociates, activating protein kinase
• Phosphorylates enzymes that produce hormone’s effects
• cAMP gets inactivated by phosphodiesteras
Adenylate Cyclase-cAMP
• Binding converts ATP into cAMP – attaches to inhibitory subunit of
protein kinase
Table 11.4
Phospholipase-C-Ca2+
2nd Messenger System
• Serves as 2nd messenger system for some hormones
• Hormone binds to surface receptor  activates G-protein 
activates phospholipase C
Phospholipase-C-Ca2+
• Phospholipase C splits a membrane phospholipid into 2nd
messengers IP3 and DAG
• IP3 diffuses through cytoplasm to ER causing Ca2+ channels
to open
• Ca2+ diffuses into cytoplasm and binds to and activates
calmodulin
• Ca2+-Calmodulin activates protein kinases
– phosphorylate enzymes that produce hormone's effects
Endocrine Glands
Many endocrine glands are organs whose primary
function is hormone secretion.
Some are mixed glands: e.g the pancreas is an
endocrine and exocrine gland.
Steroids are secreted by only the adrenal cortex
and the gonads (testis & ovary).
Pituitary Gland
•
•
Located beneath hypothalamus at base of forebrain
Also called hypophysis
Pituitary Gland
• Structurally & functionally
divided into anterior and
posterior lobes
• Hangs below hypothalamus
by infundibulum
• Anterior produces own
hormones
– Controlled by
hypothalamus
• Posterior stores and releases
hormones made in
hypothalamus
Posterior Pituitary Gland
• Stores and releases
vasopressin also called
antidiuretic hormone
(AVP or ADH) and
oxytocin
– Hormones are made in
the hypothalamus
• Supraoptic nuclei of
hypothalamus produce
ADH
• Paraventricular nuclei
produce oxytocin
• Both are transported along
hypothalamo-hypophyseal
tract to posterior pituitary
Hypothalamic Control of Posterior Pituitary
Neurons in the hypothalamus called neurosecretory cells produce
Antidiuretic hormone (ADH) that promotes reabsorption of water
from the collecting ducts in the kidneys.
ADH is released upon stimulation of osmoreceptors in the hypothalamus
in response to rise in blood osmolality. An increased osmotic pressure
increases the frequency of action potentials in the neurons that
produce ADH this causes the opening of voltage-gated Ca+ channels
which causes the release of ADH by exocytosis.
ADH secretion is inhibited by sensory input from stretch receptors in the
left atrium which are stimulated by a rise in blood volume. As the blood
becomes dilute, ADH is no longer released; this is a case of negative
feedback.
Oxytocin
Oxytocin stimulates uterine muscle contraction
during parturition
It also stimulates the release of milk from
mammary glands.
The mechanical stimulus of suckling acts via
sensory nerve impulses to the hypothalamus to
stimulate the reflex secretion of oxytocin.
The Oxytocin causes contraction of myoepithelial
cells in mammary glands and milk begins to
flow.
This mechanism is called milk letdown or milk
ejection
Anterior Pituitary Gland
• Secretes 6 trophic
hormones
• Maintain size of target
organs:
1. High blood levels
cause target to
hypertrophy
2. Low levels cause
atrophy
Anterior Pituitary
• Releasing and inhibiting
hormones from hypothalamus
– released from axon
endings into capillary bed
in median eminence
– Carried by hypothalamohypophyseal portal
system to another
capillary bed
– Diffuse into and regulate
secretion of anterior
pituitary hormones
Anterior Pituitary
• 1. Stimulation by the hypothalamus controls the release
of anterior pituitary hormones through a portal system
consisting of two capillary systems connected by a vein.
• 2. The hypothalamus produces hypothalamic-releasing
and hypothalamic-inhibiting hormones which pass to
the anterior pituitary by this portal system.
E.G
• Thyroid-releasing hormones (TRH) released from the
hypothalamus act on cells in the anterior pituitary to
stimulate the production and secretion of a specific
hormone TSH.
• Prolactin – inhibiting hormone ( PIH) it inhibits secretion
of prolactin hormone by anterior pituitary gland.
Anterior Pituitary
1. Growth hormone (GH) promotes growth, protein synthesis,
and movement of amino acids into cells
2. Thyroid stimulating hormone (TSH) stimulates thyroid to
produce and secrete T4 and T3
3. Adrenocorticotrophic hormone (ACTH) stimulates
adrenal cortex to secrete cortisol, aldosterone
4. Follicle stimulating hormone (FSH) stimulates growth of
ovarian follicles and sperm production
5. Luteinizing hormone (LH) causes ovulation and secretion
of testosterone in testes
6. Prolactin (PRL) stimulates milk production by mammary
glands
The anterior pituitary produces six different
hormones.
a. Four of these anterior pituitary hormones affect
other glands.
• 1) The thyroid-stimulating hormone (TSH)
stimulates the thyroid gland to produce and
secrete thyroxin (T4).
• 2) Adrenocorticotropic hormone (ACTH)
stimulates the adrenal cortex to release cortisol.
• 3) Gonadotropic hormones (follicle-stimulating
hormone [FSH] and luteinizing hormone
• [LH]) act on the gonads (ovaries and testes) to
secrete sex hormones.
• b. The other two hormones do not affect other glands.
• 1) Prolactin (PRL) causes the mammary glands to
produce milk.
• b) It also plays a role in carbohydrate and fat
metabolism.
• 2) Growth hormone (GH or somatotropic hormone)
• a) GH promotes skeletal and muscular growth.
• b) GH acts to stimulate the transport of amino acids into
cells and to increase the activity of ribosomes.
The hypothalamic-pituitary-gonad axis
• The hypothalamic-pituitarygonad axis (control system)
• Involves negative feedback
by target gland hormones
Higher Brain Function
and Anterior Pituitary Secretion
Hypothalamus receives input from higher brain
centers
– can affect anterior pituitary secretion
– e.g. emotional states and psychological stress can
affect circadian rhythms, menstrual cycle, and adrenal
hormones
Adrenal Glands
• Suprarenal glands – sit on
top of kidneys
• Each consists of outer
cortex and inner medulla
– arise differently during
development
Adrenal Glands
• Medulla synthesizes and secretes 80% epinephrine and
20% norepinephrine
– Controlled by sympathetic division of autonomic nervous
system
• Cortex is controlled by ACTH and secretes:
– Cortisol which inhibits glucose utilization and stimulates
gluconeogenesis (generation of glucose from noncarbohydrate carbon substrates hence helps elevate
blood glucose levels)
– Aldosterone which stimulate kidneys to reabsorb Na+
and secrete K+ regulate the levels of minerals in the
blood
– And some supplementary sex steroids (the adrenal
cortex also secretes a small amount of both male and
female sex hormones in both sexes).
Adrenal Cortex
Glucocorticoids
Cortisol promotes the breakdown of muscle
protein into amino acids taken up by the liver
from the blood.
Cortisol breaks down fatty acids rather than
carbohydrates; cortisol therefore raises blood
glucose levels.
Cortisol counteracts the inflammatory response
Mineralocorticoids
The primary target organ of Aldosterone is the kidney where it
promotes the reabsorption of Na+ and the excretion of K +.
Atrial natriuretic hormone (ANH) causes the excretion of sodium.
1) When the atria of the heart are stretched due to increased blood
volume, cardiac cells release ANH.
2) ANH inhibits the secretion of aldosterone from the adrenal cortex.
3) When sodium is excreted, so is water; the blood volume and pressure
then return to normal.
Regulation of
Blood Pressure
and Volume
Adrenal Medulla
• Hormonal effects of epinephrine last 10X longer than
norepinephrine
• Innervated by preganglionic Sympathetic fibers
• Activated during "fight or flight" response
–
–
–
–
Increased respiratory rate
Increased heart rate and cardiac output
General vasoconstriction which increases venous return
Glycogenolysis and lipolysis
Stress and the Adrenal Gland
• Stress induces a nonspecific response:
general adaptation
syndrome (GAS)
• Causes release of
ACTH and cortisol
CRH : corticotropin releasing hormone
Stress and the Adrenal Gland
• Chronic stress can induce high levels of cortisol that
cause a number of negative effects:
–
–
–
–
atrophy of hippocampus (involved in memory)
reduced sensitivity of tissues to insulin (insulin resistance)
inhibition of vagus nerve activity
suppression of growth hormone, thyroid hormone, and
gonadotropins
• Exogenous glucocorticoids used to supress the
immune response and inhibit inflammation such as in
asthma & rheumatoid arthritis. They have side effects
like hyperglycemia and osteoporosis.
(b) Long-term stress response and the adrenal cortex
Stress
Hypothalamus
Releasing
hormone
Anterior pituitary
Blood vessel
ACTH
Adrenal
gland
Adrenal cortex
secretes mineralocorticoids and
glucocorticoids.
Kidney
Effects of
mineralocorticoids:
Effects of
glucocorticoids:
• Retention of sodium
ions and water by
kidneys
• Proteins and fats broken
down and converted to
glucose, leading to
increased blood glucose
• Increased blood
volume and blood
pressure
• Partial suppression of
immune system
(a) Short-term stress response and the adrenal medulla
Stress
Nerve
Spinal cord
(cross section) signals
Hypothalamus
Nerve
cell
Adrenal medulla
secretes epinephrine
and norepinephrine.
Effects of epinephrine and norepinephrine:
• Glycogen broken down to glucose;
increased blood glucose
• Increased blood pressure
• Increased breathing rate
• Increased metabolic rate
• Change in blood flow patterns, leading to
increased alertness and decreased digestive,
excretory, and reproductive system activity
Nerve cell
Adrenal
gland
Kidney
Thyroid Gland
• Located just below the larynx
• Secretes T4 and T3 which set
basal metabolic rate (increase
the metabolic rate; there is no
one target organ—all organs
respond)
– needed for growth, development
– Secrete also calcitonin that
lowers the calcium level in the
blood and increases deposits of
calcium in the bone
• Consists of microscopic thyroid
follicles
– Outer layer follicle cells
synthesize T4
– Interior filled with colloid, a
protein-rich fluid
A scan of the thyroid 24 hrs. after
intake of radioactive iodine
Figure 11.22
Parathyroid Glands
• 4 glands embedded in lateral
lobes of posterior side of thyroid
gland
• Secrete Parathyroid hormone
(PTH)
– Most important hormone for
control of blood Ca2+ levels
11-62
Parathyroid Hormone
•
•
•
•
•
Release is stimulated by
decreased blood Ca2+
Acts on bones, kidney, and
intestines to increase blood Ca2+
levels
Under the influence of PTH, the
calcium level in blood increases
and the phosphate level
decreases.
PTH stimulates
the retention of Ca2+ (& excretion
of phosphate) by the kidney.
demineralization of bone by
promoting the activity of
osteoclasts.
Vit D promotes the intestinal
absorption of Ca2+.
Regulation of Blood
Calcium Level
Increases Ca2
uptake in
intestines
Active
vitamin D
Stimulates Ca2
uptake in kidneys
PTH
Stimulates
Ca2 release
from bones
Parathyroid
gland (behind
thyroid)
STIMULUS:
Falling blood
Ca2 level
Blood Ca2
level rises.
Homeostasis:
Blood Ca2 level
(about 10 mg/100 mL)
Islets of Langerhans
• Scattered clusters of endocrine cells in pancreas
• Contain alpha and beta cells
• Diabetes mellitus is a fairly common disease
Islets of Langerhans – Alpha Cells
• Alpha cells secrete glucagon in response to low blood
glucose
– Stimulates glycogenolysis and lipolysis
– Increases blood glucose
Islets of Langerhans – Beta Cells
• Beta cells secrete insulin in
response to high blood
glucose
– Promotes entry of glucose
into cells
– And conversion of glucose
into glycogen and fat
– Decreases blood glucose
level
11-67
Regulation
of Blood
Glucose
Level
Pineal Gland
• Located in basal
forebrain near thalamus
• Secretes melatonin in
response to activity of
suprachiasmatic
nucleus (SCN) of
hypothalamus
Pineal Gland
• SCN – primary timing center for circadian rhythms
– Reset by daily light/dark changes
• Melatonin – is involved in sleep/awake cycle
– Secreted at night and inhibited by light
– Implicated in jet-lag
The pineal gland may also be involved in human sexual
development; children in whom a brain tumor has destroyed
the pineal gland experience puberty earlier.
Thymus Gland
1. The thymus gland is a lobular gland that lies
just beneath the sternum in the upper thoracic
cavity.
2. It reaches its largest size and is most active
during childhood; with age, it shrinks and
becomes fatty.
3. Some lymphocytes that originate in the bone
marrow pass through the thymus and change
into T lymphocytes.
4. The thymus produces thymosins, which aid in
the differentiation of T cells and may stimulate
immune cells.
Sex Hormones
The ovaries, located in the pelvic cavity, produce
the female sex hormones estrogens and
progesterone.
a. Estrogens secreted at puberty stimulate the
maturation of ovaries and other sexual organs.
b. Estrogen is necessary for oocyte development.
c. It is responsible for the development of female
secondary sex characteristics: a layer of fat
beneath the skin, a larger pelvic girdle, etc.
d. Estrogen and progesterone are required for
breast development and the regulation of the
uterine cycle.
• Testosterone normally is the reason
men have larger muscles than
women.
• It is responsible for the development
of male secondary sex
characteristics.
• Anabolic Steroids: are synthetic
drugs very similar in structure and
action to male hormone
testosterone.
The Effects of Anabolic Steroid Use
Paracrine & Autocrine regulation
Local regulators such as prostaglandins (PG) are produced by
certain cells and act on neighboring cells.
PG functions
• They cause the contraction of uterine muscle
• They mediate the effects of pyrogens (chemicals believed to
affect the temperature regulatory center of the brain).
• Certain prostaglandins reduce gastric secretions, others
lower blood pressure.
d. Aspirin reduces temperature and controls pain because of
its effect on prostaglandins (inhibits cyclooxygenase, the
enzyme that synthesizes PGs).
Endocrine
gland
Major
hormone
Target
tissue
Effect
Adipose
tissue
leptin
Hypothalamus
Suppresses appetite
heart
Atrial
natriuretic
hormone
kidneys
Promotes secretion of Na+ in urine
Small
intestine
Secretin, CKK
Stomach,
liver &
pancreas
Inhibits gastric motility, stimulates
secretion of bile & pancreatic juice
kidneys
Erythropoietin
Bone
marrow
Stimulates RBC production
skin
1,25
dihydroxyvit
D3
Small
intestine
Stimulates absorption of Ca 2+
stomach
gastrin
stomach
Stimulates acid secretion
Thymus
thymopoietin
Lymph
nodes
Stimulates WBC production (
Lymphocyte )