Download Hormones

Chapter 18
The Endocrine System
• Endocrine and nervous systems work together
• Endocrine system
– hormones released into the bloodstream travel
throughout the body
– results may take hours, but last longer
• Nervous system
– certain parts release hormones into blood
– rest releases neurotransmitters excite or inhibit nerve,
muscle & gland cells
– results in milliseconds, brief duration of effects
18-1
General Functions of Hormones
• Help regulate:
–
–
–
–
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
Hormone Receptors
• Hormones only affect target cells with specific
membrane proteins called receptors
18-4
Circulating & Local Hormones
• Circulating hormones
– act on distant targets
– travel in blood
• Local hormones
– paracrines act on
neighboring cells
– autocrines act on same
cell that secreted them
18-5
Lipid-soluble Hormones
• Steroids
– lipids derived from
cholesterol on SER
– different functional
groups attached to core of
structure provide
uniqueness
• Thyroid hormones
– tyrosine ring plus attached
iodines are lipid-soluble
• Nitric oxide is gas
18-6
Water-soluble Hormones
• Amine, peptide and
protein hormones
– modified amino acids or
amino acids put together
– serotonin, melatonin,
histamine, epinephrine
– some glycoproteins
• Eicosanoids
– derived from arachidonic
acid (fatty acid)
– prostaglandins or
18-7
leukotrienes
Action of Lipid-Soluble Hormones
• Hormone diffuses
through phospholipid
bilayer & into cell
• Binds to receptor
turning on/off specific
genes
• New mRNA is formed
& directs synthesis of
new proteins
• New protein alters cell’s
activity
18-8
Action of Water-Soluble Hormones
• Can not diffuse through plasma membrane
• Hormone receptors are integral membrane
proteins
– act as first messenger
• Receptor protein activates G-protein in
membrane
• G-protein activates adenylate cyclase to
convert ATP to cAMP in the cytosol
• Cyclic AMP is the 2nd messenger
• Activates kinases in the cytosol to speed
up/slow down physiological responses
• Phosphodiesterase inactivates cAMP
quickly
• Cell response is turned off unless new
hormone molecules arrive
18-9
Hormonal Interactions
• Synergistic effect
– a second hormone, strengthens the effects of the first
– two hormones acting together for greater effect
– thyroid strengthens epinephrine’s effect upon lipolysis
• Permissive effect
– you need two hormone present for one hormone to
work properly
– estrogen & LH are both needed for oocyte production
• Antagonistic effects
– two hormones with opposite effects
– insulin promotes glycogen formation & glucagon
stimulates glycogen breakdown
18-10
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
18-11
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 9 different
releasing & inhibiting hormones
18-12
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
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
18-13
ACTH/corticotropin & MSH
Human Growth Hormone
• Produced by somatotrophs
• induces target cells to make insulin-like growth factors (IGFs) that
act locally or enter bloodstream
– common target cells of IGFs are liver, skeletal muscle, cartilage and bone
– GH + IGFs increase cell growth & cell division by increasing their uptake of
amino acids & synthesis of proteins
– stimulate lipolysis in adipose so fatty acids used for ATP
– retard use of glucose for ATP production by cells
– reduces uptake of glucose by the liver and promote breakdown of liver
glycogen– so blood glucose levels stay high enough to supply brain
• Excess of growth hormone
– raises blood glucose concentration
– pancreas releases insulin continually
– Leads to beta-cell burnout
• Diabetogenic effect
– causes diabetes mellitis if no insulin activity can occur eventually
18-14
Regulation of hGH
• Low blood sugar stimulates
release of GNRH 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
18-15
Thyroid Stimulating Hormone (TSH)
• Hypothalamus regulates thyrotroph cells
• Thyrotroph cells produce TSH
• TSH stimulates the synthesis & secretion of T3
and T4
• Metabolic rate stimulated
18-16
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
18-17
Formation of Thyroid Hormone
• Iodide trapping: follicular cells actively take
up iodine from blood
• Synthesis of thyroglobulin (TGB): follicular
cells make TGB - secreted into the follicle
lumen as the material colloid
• Iodination of colloid: iodine ions are
oxidated (I2- -> I2) by peroxidase within the
cell
– oxidized iodine then binds onto tyrosine residues
on the TGB within colloid
• Coupling of T1 and T2: forms T3 & T4
• Uptake of colloid by follicular cells:
digestion cleaves off T3 and T4
• Secretion of T3 & T4 into blood: T3 & T4
are transported in blood bound to thryoxinebinding globulin
18-18
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)
18-19
Control of T3 & T4
Secretion
• Low blood levels of
hormones stimulate
hypothalamus -> TRH
• It stimulates pituitary to
release TSH
• TSH stimulates gland to
raise blood levels
• T3 and T4 regulate
themselves through a
negative feedback loop
18-20
Parathyroid Glands
• Principal cells produce
parathyroid hormone (PTH)
• 4 pea-sized glands found on back of
• Oxyphil cell function is
thyroid gland
unknown
18-21
Parathyroid Hormone
• Raises blood calcium levels
– increases activity of osteoclasts (bone degrading cells)
– increases reabsorption of Ca+2 by kidney
– promote formation of calcitriol (vitamin D3) by kidney
which increases absorption of Ca+2 and Mg+2 by
intestinal tract
• Opposite function of calcitonin (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
18-22
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
18-23
Luteinizing Hormone (LH)
• Releasing hormones from hypothalamus stimulate
gonadotrophs
• Gonadotrophs produce LH
• In females, LH stimulates
–
–
–
–
secretion of estrogen
ovulation of 2nd oocyte from ovary
formation of corpus luteum
secretion of progesterone
• In males, stimulates interstitial cells
to secrete testosterone
18-24
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
18-25
Prolactin (PRL)
• Hypothalamus regulates
lactotroph cells
• Lactotrophs produce prolactin
• Under right conditions, prolactin
causes milk production
• Suckling reduces levels of hypothalamic
inhibition and prolactin levels rise along
with milk production
• Nursing ceases & milk production slows
18-26
Melanocyte-Stimulating Hormone
• Secreted by corticotroph cells
• Releasing hormone from hypothalamus
increases its release from the anterior pituitary
• Function not certain in humans (increase skin
pigmentation)
• May have a role in promoting sexual
performance
18-27
Adrenocorticotrophic Hormone
• Hypothalamus releasing
hormones stimulate
corticotrophs
• Corticotrophs secrete
ACTH (& MSH also)
• ACTH stimulates cells
of the adrenal cortex
18-28
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
18-29
Adrenal
Gland
• Cortex
– 3 zones
• Medulla
18-30
Mineralocorticoids
• 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 uptake from kidneys and
increased excretion of K+ into urine
18-31
• 95% of hormonal activity is due to cortisol
• neurosecretory cells secrete corticotropinreleasing hormone (CRH)
• CRH promotes the release of ACTH where
it stimulates the adrenal cortex to secrete
corticol
• Functions = helps regulate metabolism
Glucocorticoids
– increases rate of protein synthesis
– increases conversion of amino acids to
glucose – energy for protein synthesis
– stimulates lipolysis for glucose synthesis (for
energy)
– increases glucose synthesis – ATP
production provides resistance to stress by
making nutrients available for ATP
– raises BP by vasoconstriction (decreases
blood loss)
– anti-inflammatory effects reduced (skin
cream)
• reduces release of histamine from mast cells
• decreases capillary permeability
• depresses phagocytosis
18-32
Androgens
• Small amount of male hormone produced
by the zona reticularis
– insignificant in males
– may contribute to sex drive in females
– is converted to estrogen in postmenopausal
females
18-33
Adrenal Medulla
• 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
AM
18-34
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
18-35
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
18-36
Antidiuretic Hormone (ADH)
• Known as vasopressin
• Functions
– decrease urine production
– decrease sweating
– increase BP
• Dehydration
– ADH released
• Overhydration
– ADH inhibited
18-37
Pancreas
•
•
•
•
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
18-38
• 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
F cells produce pancreatic polypeptide
18-39
Regulation of Glucagon & Insulin Secretion
• Low blood glucose
stimulates release of
glucagon
• High blood glucose
stimulates secretion of
insulin
18-40
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
18-41
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
18-42
Eicosanoids
• Local hormones released by all body cells normally and upon
trauma
• synthesized from arachidonic acid (fatty acid)
• Leukotrienes influence WBCs – inflammation & allergic
response
• 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
– PGs are synthesized by an enzyme complex containing the enzymes
COX1 and COX2
– Aspirin and ibuprofen can inhibit activity of COX1 isoform – short term
anti-inflammatory
– Vioxx, Bextra and Celebrex inhibit activity of COX2 isoform – long
term anti-inflammatory
18-43
Pituitary Gland
Disorders
• Hyposecretion during childhood = pituitary dwarfism (proportional,
childlike body)
• Hypersecretion during childhood = giantism
– very tall, normal proportions
• Hypersecretion as adult = acromegaly
– growth of hands, feet, facial features & thickening of skin
Thyroid Gland Disorders
• Hyposecretion of TSH during infancy results in dwarfism & retardation called
cretinism
• Hypothyroidism - undersecretion of T3 and T4
– Caused by low production of TSH
– in adults produces sensitivity to cold, low body temp. weight gain & mental dullness
• Hyperthyroidism – oversecretion of T3 and T4 (Grave’s disease)
– caused by the inability of the thyroid to respond to TSH levels
– weight loss, cardiac complications, increased fluid behind the eyes & goiter = enlarged
thyroid
18-44
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
– hypoglycemia, muscle weakness, low BP, dehydration
due to decreased Na+ in blood
– mimics skin darkening effects of MSH
– potential cardiac arrest
18-45
Diabetes Mellitus & Hyperinsulinism
• 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
18-46