lecture #10

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The Endocrine System
• Endocrine and nervous systems work together
• Endocrine system
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•
hormones released into the bloodstream travel throughout the body
target is usually far from site of synthesis
binds to receptors on or in target
targets = cells throughout the body
results may take hours, but last longer
Nervous system
– certain parts release hormones into blood
– rest releases neurotransmitters that excite or inhibit nerve, muscle & gland
cells
– results in milliseconds, brief duration of effects
18-1
General Functions of Hormones
• Help regulate:
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extracellular fluid
metabolism
biological clock
contraction of cardiac &
smooth muscle
– glandular secretion
– some immune functions
• Growth & development
• Reproduction
18-2
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
18-3
Extracellular Signaling:
Mechanisms
• most signals produced by cells within the body bind to
receptors that are specific for that signal
• most receptors are found on the cell surface
• although some can be found within the cell!
• binding of the signal (ligand) to the receptor results in a
series of events (signal transduction) within the cell that
changes the cells function
– e.g. may change the transcription rate of a gene – effects protein
production
18-4
Hormones: Mechanisms of Signaling
•
hormone producing cell = endocrine cell
– e.g. thyroid, pituitary
•
Autocrine signaling
– cell responds to the hormone it produces
•
Paracrine signaling
– local action
– local hormone (paracrine hormones)
act on neighboring cells
– autocrines act on same cell that secreted
them
•
Endocrine signaling
– circulating hormones (endocrine
hormones)
– act on distant targets
– travel in blood
18-5
Types of Hormones
• water-soluble
• lipid -soluble
18-6
Lipid-soluble Hormones
• Steroids
– lipids derived from cholesterol
– made in SER
– different functional groups attached to
core of structure provide uniqueness
testosterone
aldosterone
• e.g. cortisol, progesterone, estrogen,
testosterone, aldosterone
• Thyroid hormones
cortisol
– tyrosine ring plus attached iodines
– are lipid-soluble
• Retinoic acid
– lipids derived from retinol (vitamin A)
– regulate proliferation, differentiation and
death of many cell types
• some vitamins can acts a lipid-soluble
hormones
– e.g. vitamin D
• Nitric oxide (NO)
- gas
18-7
Lipid-soluble Hormones
• Eicosanoids
– prostaglandins or leukotrienes
– derived from arachidonic acid
(fatty acid)
– AA is converted either into
prostaglandin H or into the
leukotrienes
– conversion of AA into
prostaglandins is regulated by the
COX enzymes
– both act in the inflammatory
reaction
• e.g. stimulate smooth muscle cells
to contract
• e.g. stimulate nerve cells – pain
18-8
Water-soluble Hormones
• Amine, peptide and protein hormones
– modified amino acids to protein chains
– serotonin, melatonin, histamine,
epinephrine, insulin, dopamine
– protein hormones – comprised of one or
many polypeptide chains
• insulin, glucagon
– peptide hormones – comprised of chains
of amino acids
• e.g. growth hormone, oxytocin
– amine hormones – derived from the
amino acids tyrosine or tryptophan
• epinephrine (tyrosine and
phenylalanine), serotonin (tryptophan),
dopamine (tyrosine)
insulin
– can also act as neurotransmitters
18-9
Action of Lipid-Soluble Hormones:
Endogenous signaling
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•
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•
•
Hormone must be carried by a
transport protein that allows it to
dissolve within the aqueous (watery)
environment of the blood plasma
Hormone diffuses through
phospholipid bilayer & into cell
the receptor is located within the cell
(cytoplasm or the nucleus)
binding of H to R results in its
translocation into the nucleus
the H then binds directly to specific
sequences within the DNA =
response elements
this binding turns on/off specific
genes – activates or inhibits gene
transcription
if turned on - new mRNA is formed
& directs synthesis of new proteins
new protein alters cell’s activity
if turned off – no new protein results
and the cell’s activity is altered
18-10
Action of Lipid-Soluble Hormones
• some lipid-soluble hormone don’t cross the
plasma membrane – too large
• therefore they bind with receptors on the
cell surface and trigger signaling events
within the cells
– signal similar to water-soluble hormones
– e.g. prostaglandins
18-11
Action of Water-Soluble Hormones
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•
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easily travels through the blood - hydrophilic
but cannot diffuse through plasma membrane!
therefore absolutely requires the expression of receptors
on the cell surface – integral membrane proteins that act
as first messenger
the receptor protein activates a series of signaling events
within the cells
– e.g. epinephrine binds to receptor and activates an
adjacent G-protein in membrane
– G-protein activates adenylate cyclase to convert ATP
to cyclic AMP (cAMP) in the cytosol
– cAMP is the 2nd messenger
– cAMP activates a series of proteins in the cytosol
called kinases
– kinases act to phosphorylate their targets – either
activating them or inhibiting them
– this speeds up/slows down physiological responses
within the cell
– phosphodiesterase inactivates cAMP quickly
many second messengers are made in cells in response
to specific hormones
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•
•
e.g. calcium, IP3, DAG
Cell response is turned off unless new hormone
molecules arrive
this mechanism allows for amplification – one H-R
combination can activate two G proteins which activates 4
kinases which activate 16 more kinases etc…….
18-12
Hormonal Interactions
• Permissive effect
– Second hormone permits the action of the first
– estrogen & LH are both needed for oocyte production
• Synergistic effect
– two hormones act together for greater effect (vs.
individually)
– thyroid strengthens epinephrine’s effect upon lipolysis
• Antagonistic effects
– two hormones with opposite effects
– insulin promotes glycogen formation & glucagon
stimulates glycogen breakdown
18-13
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
18-14
Hypothalamus and Pituitary Gland
• Both are master endocrine glands since their hormones
control other endocrine glands
• Hypothalamus is a section of brain above where pituitary
gland is suspended from stalk
• Hypothalamus receives input from cortex, thalamus,
limbic system & internal organs
• Hypothalamus controls pituitary gland with 7 different
releasing & inhibiting hormones – PLUS two additional
hormones (ADH & oxytocin)
18-15
•hypothalamus
-Emotions, autonomic
functions, hormone production
-mamillary bodies – serve as
relay stations for reflexes
related to smell
-supraoptic and preoptic
regions that function in vision
-major functions:
1. control of the ANS –
integrates signals from the
ANS (regulated smooth and
cardiac muscle contraction)
major regulator of visceral
activities (heart rate, food
movements, contraction of
bladder)
2. produces hormones &
connects with pituitary to
regulate its activity
3. regulates emotional and behavioral patterns – rage,
aggression, pain and pleasure + sexual arousal
4. regulates eating & drinking – hypothalamus contains
a thirst center which responds to a rise in osmotic
pressure in the ECF (dehydration)
5. controls body temperature – monitors temp of blood
flowing through the hypothalamus
18-16
Pituitary
Gland
•
•
cells secrete 9 different hormones
regulates the activity of the pituitary through
its secretion of 7 specific releasing and
inhibiting hormones
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•
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median eminence
e.g. pituitary hormone = somatotropin
hypothalmic hormones = somatotropin
releasing hormone (SRH) and somatotropin
inhibiting hormone (SIH)
also secretes two specific hormones that are
stored in the pituitary – oxytocin and antidiuretic hormone (ADH)
portion that marks the connection with the
pituitary = median eminence
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near the ME is a group of cells =
neurosecretory cells
secrete the hypothalmic releasing and inhibiting
hormones that regulate the pituitary
stored in synaptic vesicles
released upon production of an action potential
via exocytosis into the blood stream
Diffusion down to the anterior pituitary
18-17
Pituitary
Gland
• 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
-hypothalamic hormones
(releasing hormones) reach the
pituitary via a portal system of
capillaries = hypophyseal portal
system (HPS)
-flow of blood from the hypothal.
into portal veins that carry blood to
the capillaries of the ant pituitary
-superior hypophyseal arteries are
branches off of the internal carotid-bring blood into the hypothal.
-where the hypothal. and infundibulum
meet they divide into the primary
plexus of the HPS
-from this plexus blood drains into
hypophyseal portal veins
-at the anterior pituitary these portal
veins divide into the secondary plexus
of the HPS
-release of the hypothalmic releasing &
inhibiting hormones into the primary
plexus of the HPS and travel to the
secondary plexus
18-18
Anterior
Pituitary
Gland
Hormones:
human growth hormone- hGH
thyroid stimulating - TSH
follicle stimulating- FSH
leutinizing hormone - LH
prolactin
adrenocorticotropin - ACTH
melanocyte stimulating - MSH
• 5 types of cells:
• somatotrophs: secrete
hGH/somatotropin
• thyrotrophs: secrete
TSH/thyrotropin
• gonadotrophs: secrete
FSH, LH
• lactotrophs: secrete
prolactin
• corticotrophs: secrete
ACTH/corticotropin &
MSH
18-19
Anterior Pituitary
Gland: Control of Secretion
• first level of regulation: releasing and
inhibiting hormones of the
hypothalamus
• second level is negative feedback by
hormones release by the target gland
– e.g. corticotropin (ACTH) release
stimulated by CRH/corticotropin releasing
hormone
– travels to anterior pituitary and stimulates
release of ACTH
– ACTH travels to the adrenal gland –
stimulates production and secretion of
cortisol
– increase of cortisol beyond the normal range
triggers release of CIH/corticotropin
inhibiting hormone
– CIH shuts down the secretion of ACTh by
the anterior pituitary
18-20
Human Growth Hormone
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Produced by somatotrophs
release is stimulated by GHRH from the hypothalamus
promotes synthesis of insulin-like growth factors
– IGFs are made primarily by the liver
– common target cells for IGFs: skeletal muscle, cartilage and bone cells
– increases cell growth & cell division by increasing their uptake of amino acids & synthesis of
proteins
•
hGH also:
– stimulates lipolysis in adipose - so fatty acids can be used for ATP
– stimulates synthesis and release of glucose into the blood by the liver = gluconeogenesis
– retards use of glucose for ATP production so blood glucose levels remain high enough to
supply brain
– hGH secretion is promoted by decreased fatty acids and amino acids in the blood, decreased
blood sugar, deep sleep, increased activity by the sympathetic NS, hormones (glucagon,
estrogen, cortisol and insulin)
•
Excess of growth hormone
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raises blood glucose concentration
pancreas releases insulin continually
beta-cell burnout
Diabetogenic effect: eventually causes diabetes mellitis if no insulin activity
occurs
18-21
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
18-22
Medical application
• 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
18-23
Thyroid Stimulating Hormone (TSH)
• Hypothalamus regulates thyrotroph cells
• Thyrotroph cells produce TSH
• TSH stimulates the synthesis & secretion of T3
and T4
• Metabolic rate stimulated
18-24
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
18-25
Luteinizing Hormone (LH)
• Releasing hormones from hypothalamus stimulate
gonadotrophs
• Gonadotrophs produce LH
• In females, LH stimulates
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secretion of estrogen
ovulation of 2nd oocyte from ovary
formation of corpus luteum
secretion of progesterone
• In males, stimulates interstitial cells
to secrete testosterone
18-26
Prolactin (PRL)
• Hypothalamus regulates lactotroph cells
• Lactotrophs produce prolactin (also produced by breast tissue)
– during pregnancy – high levels of estrogen contribute
• Under right conditions, prolactin increases mammary gland size
and causes milk production
– during pregnancy high levels of progesterone prevent milk let-down
– also contributes to female orgasm, proliferation of oligodendrocytes
(!)
• hypothalamus normally inhibits prolactin production when not
pregnant
– arcuate nucleus produces dopamine which inhibits lactotroph activity
• Suckling reduces levels of hypothalamic inhibition and prolactin
levels rise along with milk production
– milk let-down also requires action of oxytocin (promoted also by
suckling)
• also provides feelings of sexual gratification after intercourse
– counteracts dopamine (sexual arousal) – produces a “sexual
refractory” period
18-27
Adrenocorticotrophic Hormone
• Hypothalamus releasing
hormones stimulate
corticotrophs
• Corticotrophs secrete
ACTH & MSH
• ACTH stimulates cells
of the adrenal cortex that
produce glucocorticoids
18-28
Melanocyte-Stimulating Hormone
• Secreted by corticotroph cells under the control
of MRH (MSH-releasing hormone)
• Releasing hormone from hypothalamus
increases its release from the anterior pituitary
• Function not certain in humans (increase skin
pigmentation in frogs )
18-29
Posterior Pituitary Gland (Neurohypophysis)
• Does not synthesize
hormones
• Consists of axon
terminals of hypothalamic
neurons
• Neurons release two
neurotransmitters that
enter capillaries
– antidiuretic hormone
– oxytocin
18-30
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
– suckling & hearing baby’s cry stimulates milk ejection
– hormone causes muscle contraction & milk ejection
18-31
Antidiuretic Hormone (ADH)
• Known as vasopressin
• Functions
– decrease urine production
– decrease sweating
– increase BP
• Dehydration
– ADH released
• Overhydration
– ADH inhibited
18-32
The peripheral endocrine glands
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thyroid and parathyroid
adrenal glands
ovaries and testes
pancreas
18-33
Thyroid Gland
• comprised of microscopic sacs
called follicles = follicular cells
making up the walls, surrounds a
lumen
• synthesize T3 & T4 (thyroxin)
• In between follicular cells cells are
parafollicular cells
•On each side of trachea is lobe of thyroid
•connected by an isthmus
•Weighs 1 oz & has rich blood supply
– produce calcitonin
18-34
Formation of Thyroid Hormone
• Iodide trapping: follicular cells actively take up
iodide ions from blood
• Synthesis of thyroglobulin (TGB): RER of follicular
cells make TGB - secreted into the follicle lumen
• Iodination of colloid: iodide ions are oxidated (i.e
reform I2) by peroxidase, iodine molecule then binds
onto tyrosine residues on the TGB = known as colloid
– this oxidation is required because negatively charges
ions can’t bind onto the tyrosine amino acids
• Coupling of T1 and T2: one iodine molecule = T1;
two iodine molecules = T2
– Inside the lumen - form T3 & T4
– T2 + T2 = T4; T1 + T2 = T3
• Uptake of colloid by follicular cells: colloid reenters
the follicular cells by pinocytosis, merge with
lysozymes
– digestion of TGB cleaves off T3 and T4 hormones
• Secretion of T3 & T4 into blood: T3 & T4 are
transported in blood bound to thryoxine-binding
18-35
globulin (TBG)
Actions of Thyroid
Hormones
• T3 & T4 = increases metabolic
rate
stimulates synthesis of protein
stimulates breakdown of fats
stimulates cholesterol excretion
increases use of glucose &
oxygen (ATP production)
increases body temperature
(calorigenic effect)
18-36
Control of T3 & T4
Secretion
• Low blood levels of
hormones stimulate
hypothalamus -> TRH
• It stimulates pituitary to
release TSH
• TSH stimulates thyroid
gland to raise blood levels of
T3 and T4
• T3 and T4 regulate
themselves through a
negative feedback loop
18-37
Medical application: Thyroid
disorders
-hyperthyroidism:
-most common form – Grave’s disease
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7 to 10 times more common in females
autoimmune disorder
antibodies that mimic the action of TSH
enlargened thyroid and exophthalmos (edema behind the eyes)
hypothyroidism: reduced production of TSH and thryoid hormones
-common treatment – oral L-thyroxin
- can produce myxedema in the adult
• more common in females
• edema within the facial tissues, slow heart rate, low body temperature
•
congenital hypothyroidism
– causes severe mental retardation and stunted bone growth
– babies appear normal due to maternal thyroid hormones – so testing is required
18-38
Parathyroid Glands
• Principal cells (chief cells)
produce parathyroid
• 4 pea-sized glands found on back of
hormone (PTH)
thyroid gland
• Oxyphil cell function is
unknown
18-39
Parathyroid Hormone
• Raises blood calcium levels (also regulates Mg and
phosphate levels
– increases activity of osteoclasts, increases # of OCs
• releases calcium and HPO4 into the blood
– acts on the kidneys to increase reabsorption of Ca+2 back into
the blood (also same for Mg)
• increases loss of HPO4 into the urine – decreases the overall level of
HPO4 in the blood
– promotes formation of calcitriol (vitamin D3) by kidney which
increases absorption of Ca+2 and Mg+2 by intestinal tract
• Opposite function of calcitonin (CT = thyroid)
• High or low blood levels of Ca+2 stimulate the release of different
hormones --- PTH or CT
– high level of calcium in blood - release of calcitonin by parafollicular cells,
promotes uptake of calcium into bone matrix, lowers blood calcium
– low level of calcium in blood - release of PTH by parathyroid glands,
promotes release of calcium from bone, raises blood calcium
18-40
Adrenal Glands
• Cortex derived from
mesoderm
• Medulla derived from
ectoderm
• One on top of each kidney
• 3 x 3 x 1 cm in size and weighs 5 grams
• Cortex produces 3 different types of
hormones from 3 zones of cortex:
mineralcorticoids (aldosterone),
glucocorticoids (cortisol) & androgens
• Medulla produces epinephrine &
norepinephrine
18-41
Adrenal
Gland
• Cortex
– 3 zones
• Medulla
18-42
Mineralocorticoids
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•
•
from the zona glomerulosa of the adrenal
cortex
95% of these hormones - aldosterone
Functions
– increase reabsorption of Na+ with Cl- ,
bicarbonate and water following it
– promotes excretion of K+ and H+
•
•
•
dehydration, hemorrhage (decrease in blood
volume) - decreases blood pressure - secretion
of renin from kidneys which stimulates
angiotensin II release from lungs - stimulates
aldosterone release from adrenal cortex increases water and Na uptake from kidneys
and increased excretion of K+ and H+ into
urine
the increase water reabsorption back into the
blood increases blood volume and pressure
angiotensin II also stimulates contraction of
smooth muscle within arterioles
18-43
• from the zona fasiculata of the adrenal
cortex
• 95% of hormonal activity is due to cortisol
• neurosecretory cells secrete corticotropinreleasing hormone (CRH)
• CRH promotes the release of ACTH which
stimulates the adrenal cortex to secrete
cortisol
• Functions = helps regulate metabolism &
provides resistance to stress
Glucocorticoids
– increases rate of protein breakdown &
lipolysis
– conversion of amino acids to glucose for
ATP synthesis
– stimulates lipolysis for ATP synthesis
– provides resistance to stress by making
nutrients available for ATP production
– anti-inflammatory effects reduced (skin
cream)
• reduces release of histamine from mast cells
• decreases capillary permeability
• depresses phagocytosis
18-44
Androgens
• Small amount of male hormone produced by the
zona reticularis
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–
–
–
–
insignificant in males
may contribute to sex drive in females
secreted as dehydroepiandrosterone (DHEA)
is converted to estrogen in postmenopausal females
also used by body builders since it is a precursor to
functional testosterone
• high dose administration to be useful – side effects?
– http://skepdic.com/dhea.html
– http://en.wikipedia.org/wiki/Dehydroepiandrosterone
18-45
Adrenal Medulla
• modified sympathetic ganglion – part of the ANS!
• the cells lack axons are cluster around blood vessels
• these hormone producing cells = Chromaffin cells
receive direct innervation from sympathetic
nervous system
• Produce epinephrine & norepinephrine
• Hormones are sympathomimetic
– effects mimic those produced by sympathetic NS
– cause fight-flight behavior
• sympathetic preganglionic neurons secrete
acetylcholine - which stimulates secretion by the
adrenal medulla
18-46
Medical application: 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
Addison’s disease
• Hyposecretion of glucocorticoids, mineralcorticoids
– hypoglycemia, muscle weakness, low BP, dehydration due to decreased
Na+ in blood
– mimics skin darkening effects of MSH
– potential cardiac arrest
18-47
Pancreas
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•
•
•
Organ (5 inches) consists of head, body & tail
Cells (99%) in acini produce digestive enzymes
Endocrine cells in pancreatic islets produce hormones
Exocrine acinar cells surround a small duct = digestive
enzymes
18-48
• Endocrine cells secrete near a capillary
• 1 to 2 million
pancreatic islets
• Contains 4 types of
endocrine cells
•
•
•
•
Alpha cells (20%) produce glucagon
Beta cells (70%) produce insulin
Delta cells (5%) produce somatostatin or GHIH
F cells produce pancreatic polypeptide
18-49
Regulation of Glucagon & Insulin Secretion
• Low blood glucose
stimulates release of
glucagon
• High blood glucose
stimulates secretion of
insulin
18-50
Medical application: Diabetes Mellitus
• Diabetes mellitus marked by hyperglycemia
– excessive urine production (polyuria)
– excessive thirst (polydipsia)
– excessive eating (polyphagia)
• Type I----deficiency of insulin (under 20)
• Type II---adult onset
– drug stimulates secretion of insulin by beta cells
– cells may be less sensitive to hormone
18-51
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
18-52
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
• Melatonin secretion
produces sleepiness
- occurs during
darkness due to lack
of stimulation from
sympathetic
ganglion
•light strikes retina and stimulates
suprachiasmatic region of
hypothalamus
stimulates sympathetic ganglion
which then stimulates the
pineal gland
light -> NE -> no melatonin
dark -> lack of NE -> melatonin
18-53
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
18-54
The stress response
• helpful stress = eustress
• stressor = any disturbance in the homeostatic balance of
the human body
• when homeostasis can counteract these stressors the body
remains within normal physiologic parameters
• if not – a series of reactions occurs = stress response
– three stages:
• 1. initial fight or flight response
• 2. slower resistance reaction
• 3. exhaustion
18-55
•
fight or flight
– initiated by nerve impulses of
the hypothalamus to the adrenal
medulla (ANS)
– release of epinephrine and
norepinephrine
– prepares the body for
immediate physical response
– short lived response
•
resistance
– initiated by hypothalmic
releasing hormones
– CRH, GHRH and TRH
– helps the body continue fighting
the stressor
– if the body fails to combat the
stressor, our body
enters the last stage
•
exhaustion
– resources become depleted so
they can no longer continue the
resistance stage
– prolonged exposure to cortisol
can cause wasting of skeletal
muscle, suppression of the
immune system, ulceration of
the GI tract and failure of the
beta cells of the pancreas to
make insulin (diabetes)
-increased blood sugar
from breakdown or neogenesis
-increased
glucose used
to make ATP
and drive
metabolism
18-56
Stress and Disease
• can lead to specific diseases by temporarily inhibiting the
immune system
• includes gastritis, ulcerative colitis, irritable bowel
syndrome, migraines, anxiety, hypertension, asthma,
rheumatoid arthritis
• role for interleukin-1 (IL-1) which is secreted by
macrophages in the immune system
• IL-1 can stimulate secretion of ACTH by the anterior
pituitary
– causes production of cortisol
– increased resistance to stress – good
– BUT if not controlled – exhaustion – bad!
18-57
Eicosanoids
•
•
•
•
Local hormones released by all body cells
synthesized from arachidonic acid
Leukotrienes influence WBCs & inflammation
Prostaglandins alter
– smooth muscle contraction, glandular secretion, blood flow,
platelet function, nerve transmission, metabolism etc.
– Ibuprofen & other nonsteroidal anti-inflammatory drugs
treat pain, fever & inflammation by inhibiting prostaglandin
synthesis
18-58
Nonsteroidal Anti-inflammatory Drugs
• Answer to how aspirin or ibuprofen works
was discovered in 1971
– inhibit a key enzyme in prostaglandin synthesis
(COX) without affecting the synthesis of
leukotrienes
• Treat a variety of inflammatory disorders
– rheumatoid arthritis
18-59
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)
18-60
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