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Transcript
Endocrine System
Chapter 16
Overview
• Overall goal of endocrine system: maintain a
stable internal environment (homeostasis)
• Endocrine glands are “ductless glands”
• Endocrine glands secrete hormones which
travel through the blood to a target cell
– Receptor must be present on target cell
• Glands of the endocrine system are present
throughout the body
• Most cells are regulated by the endocrine
system
Endocrine vs Nervous System
• Both systems function to maintain homeostasis
• Main differences:
Feature
Endocrine System
Nervous System
Effector cells
Target cells throughout the
body
Postsynaptic cells in muscle
and glandular tissue only
Chemical messenger
Hormone
Neurotransmitter
Distance traveled by
messenger
Long – in blood
Short – across synaptic cleft
Regulatory effects
Slow to appear; long-lasting
Appear rapidly; short
Endocrine vs Nervous System
Major Endocrine
Glands
Classification of Hormones
• Classified by Function
– Tropic hormones: target other endocrine
glands and stimulate their growth & secretion
– Sex hormones: target reproductive tissues
– Anabolic hormones: stimulate anabolism in
their target cell
Classification of Hormones
• Classified by Chemical Structure
– Steroid Hormones
• Derived from cholesterol
• Lipid soluble; can pass through phospholipid
bilayer
– Nonsteriod Hormones
• Synthesized from amino acids
• Proteins, Glycoproteins, peptides, amino acid
derivatives (Fig 16-3)
Chemical Classifications of Hormones
How Hormones Work
• Hormones bind to receptors on target
cells
– Lock & key
• Hormone-receptor interactions
produce regulatory changes within
the target cell
– Ex: initiating protein synthesis;
activation/inactivation of enzymes;
opening/closing of ion channels
• Endocrine glands produce more
hormone molecules than necessary
to hit the target cells
– Excess hormones are excreted in urine
or broken down by metabolic processes
How Hormones Work
• Synergism: combinations of hormones
have a greater effect on the target cell
compared to a single hormone acting
alone
• Permissiveness: a small amount of one
hormone allows a second hormone to
exhibit its full effect on the target cell
• Antagonism: two hormones produce
opposite effects
Mechanisms of Steroid Hormone Action
• Steroids are lipids  not soluble in blood plasma
(mostly H2O)
• In blood steroids attach to plasma proteins
• Steroid reaches a target cell  dissociates from
plasma protein  diffuses into target cell
• In the nucleus a hormone-receptor complex is
formed
• Hormone-receptor complexes in the nucleus trigger
protein synthesis (transcription & translation)
• Increase steroid = increase response (protein
synthesis)
• Regulatory effects of hormones are slow to appear
Mechanisms of Steroid Hormone Action
Mechanisms of Nonsteriod Hormone Action
• Nonsteroid hormones operate according to
the second messenger hypothesis
– Nonsteroid hormone is the “1st messenger” and
binds to a receptor on the plasma membrane of
the target cell
– The “message” is relayed inside the cell to a “2nd
messenger” which triggers the appropriate
cellular response
Second Messenger Mechanism
1.
2.
3.
Nonsteroid
hormone (1st
messenger) binds
with receptor on
plasma membrane
Hormone-receptor
complex activates a
membrane protein
called the G protein
G protein activates
guanosine
triphosphate (GTP)
which also
activates another
membrane protein
(adenyl cyclase)
Second Messenger Mechanism
4.
5.
6.
Adenyl cyclase
removes 2
phosphate groups
from ATP creating
cyclic adenosine
monophosphate
(cAMP) (second
mesenger)
cAMP activates or
inactivates protein
kinases
Protein kinases
activate specific
intracellular
enzymes
Second Messenger Mechanism
7.
Enzymes influence
specific cellular
reactions (target
cell’s response to
hormone)
Second Messenger Mechanism
Summary:
• Hormone or 1st messenger binds to plasma
membrane receptor
• Triggers formation of intracellular 2nd messenger
• 2nd messenger activates cascade of chemical
reactions
• Target cell’s response to the hormone is
produced
Another Second Messenger
• Some hormones produce effects in target cells by
triggering opening of calcium channels
–
–
–
–
–
–
Hormone binds to receptor on plasma membrane
Ca2+ channels open
Ca2+ binds with calmodulin
Ca2+/Calmodulin complex acts as 2nd messenger
Enzymes are activated/inactivated
Target cell’s response is produced
Calcium-Calmodulin as 2nd Messenger
Regulation of Hormone Secretion
• Hormone secretion is controlled by a
negative feedback loop
– Ex: parathyroid hormone (PTH) and blood
calcium levels (fig 16-10)
– Ex: insulin and blood glucose levels
Endocrine
Feedback
Loop
Hyper vs Hyposecretion
• Tumors or abnormalities of the endocrine
glands cause secretion of too much or too
little hormone
• Hypersecretion: production of too much
hormone
• Hyposecretion: production of too little
hormone
– Results in lack of target cell response
– Also caused by target cell insensitivity
Regulation of Target Cell Sensitivity
• Sensitivity of target cell depends on number
of receptors it has for a specific hormone
• Receptors are constantly being broken down
and re-synthesized by the cell
• Up-regulation: synthesis of new receptors >
degeneration of old receptors
– Increase target cell sensitivity to that particular
hormone
• Down-regulation: synthesis of new receptors
< degeneration of old receptors
– Decrease target cell sensitivity
Pituitary Gland
• Also called hypophysis
• Located on ventral surface of brain, inferior to the
hypothalamus
• “Master gland” because functions are crucial to life
• Composed of two parts: Anterior Pituitary and
Posterior Pituitary
Anterior Pituitary
• Hormones secreted from Anterior Pituitary:
– Growth Hormone
– Prolactin
– Trophic hormones
• Thyroid-stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)
• Gonadotropic hormones
– Follicle-stimulating hormone (FSH)
– Luteinizing hormone (LH)
Growth Hormone
• Growth Hormone (GH) – promotes growth by
stimulating protein anabolism
• Increased protein anabolism allows increased
growth rate
• Target cells:
– Promotes growth of bone and muscle
• GH has a hyperglycemic effect; antagonist of
insulin
– Hyperglycemic effect because GH stimulates fat
metabolism
– Interaction vital to maintaining homeostasis of blood
glucose levels
Growth Hormone Abnormalities
• Hypersecretion
– Prior to ossification of the epiphyseal plates
hypersections of GH results in rapid skeletal
growth  Gigantism
– After closure of epiphyseal plates
hypersecretion causes cartilage to continue to
form new bone  Acromegaly
• Distorted appearance; enlarged hands, feet, face,
jaw; thickened skin
Growth Hormone Abnormalities
• Hyposecretion
– Results in stunted body growth  pituitary
dwarfism
– Treated with genetically engineered growth
hormone
Prolactin (PRL)
•
•
•
•
Also called lactogenic hormone
Initiates milk secretion (lactation)
Target cells: Mammary glands
During pregnancy PRL promotes
development of breasts
• At birth PRL stimulates milk production
Prolactin Abnormalities
• Hypersecretion:
– Lactation in non-nursing women
– Disruption of menstrual cycle
– Impotence in men
• Hyposecretion:
– Insignificant unless mother wishes to
breastfeed
Trophic Hormones
• Review: a trophic hormone stimulate
effects of other endocrine glands
• Trophic hormones released from anterior
pituitary gland:
– Thyroid-stimulating hormone (TSH)
– Adrenocorticotropic hormone (ACTH)
– Gonadotrophic hormones
• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)
Thyroid-stimulating hormone (TSH)
• Promotes and maintains growth and
development of thyroid gland
• Required for thyroid gland to secrete its
hormones
Adrenocorticotropic hormone
(ACTH)
• Promotes and maintains normal growth
and development of the cortex (outer
portion) of the adrenal gland
• Required for adrenal cortex to secrete its
hormone
Gonadotrophic hormones
• Target cells: gonads (testes & ovaries)
• Follicle-stimulating hormone (FSH)
– Females:
• Stimulates growth & development of an ovum that
is released each month during ovulation
• Stimulate estrogen release from the ovaries
– Males
• Stimulates development of seminiferous tubules
and maintains sperm production in the testes
Gonadotrophic hormones
• Luteinizing hormone (LH)
– Females:
• Triggers ovulation
• Promotes development of corpus luteum which
secretes progesterone and estrogen; these
hormones help maintain pregnancy
– Males:
• Stimulates cells of the testes to synthesize and
secrete testosterone
Control of Anterior Pituitary Secretion
• The hypothalamus releases chemical
called releasing hormones which
influence hormone secretion from the
anterior pituitary gland
• This regulatory mechanism is a negative
feedback loop
Posterior Pituitary
• Hormones secreted from Posterior Pituitary:
– Antidiuretic Hormone (ADH)
– Oxytocin (OH)
Antidiuretic Hormone (ADH)
• Target cells: kidney
• Prevents formation of large volumes of
dilute urine
• Antidiuresis
• Helps conserve water balance
• Example:
– Blood is hypertonic  change detected by
osmoreceptors  ADH is released  water
reabsorbed in kidneys and returned to blood
ADH Abnormalities
• Hyposecretion
–
–
–
–
Diabetes insipidus
Increased urine output of dilute urine
“high and dry”
Na+ levels are increased; ICF dehydrated
• Hypersecretion
– Syndrome of inappropriate antidiuretic hormone
(SIADH)
– Decreased urine output
– Fluid overload; low Na+ levels
Oxytocin (OT)
• Target cells: mammary glands & uterine smooth
muscle
• Operates on a positive feedback loop
• Stimulates uterine smooth muscle contractions
– During childbirth stretching of receptors causes continued
release of oxytocin until after delivery of the placenta
• Ejection of milk into ducts of the breast of lactating
women
– When breastfeeding the suckling action of the baby causes
secretion of additional oxytocin increasing milk production
– Breastfeeding also helps the uterus continue to contract
back to normal size during the postpartum period
Pineal Body
• Regulates the body’s biological clock
– Patterns of eating
– Sleeping
– Female reproductive cycle
– Behavior
• Secretes melatonin
– Induces sleep
– Secretion is inhibited by sunlight
– Target cell in humans is unknown
Melatonin & Seasonal Affective
Disorder
• Also know as “winter depression”
• During shorter days, melatonin secretion
increases causes a depressed feeling in
affected patients
• Treatment
– Exposure to high-intensity lights to inhibit
melatonin secretion
Thyroid Gland
• The thyroid gland is composed of two lateral
lobes connected by an isthmus
• Located on the anterior and lateral surfaces
of the trachea, below the larynx
Thyroid Hormones
• Tetraiodothyronine or thyroxine (T4)
– Most abundant thyroid hormone
– Contains 4 iodine atoms
– May have effect on target cells, but mostly
serve as precursor to T3
• Triodothyronine (T3)
– “principal thyroid hormone”
– Contains 3 iodine atoms
Thyroid Hormones
• Both hormone bind to plasma proteins once
secreted into the bloodstream
• Function:
– Regulate metabolic rate of all cells
– Regulate cell growth
– Regulate tissue differentiation
• Target cells: “general” because thyroid
hormones can potentially interact with all
cells of the body
Hypersection
• Graves Disease
– Autoimmune condition (thyroid stimulating
antibodies causes abnormal secretion)
– Weight loss
– Increases basal metabolic rate
– Increased heart and respiratory rate
– exophthalmos
Exophthalmos
Hyposecretion of Thyroid Hormone
• Cretinism – develops during the growth years
due to hypothyroidism
– Low metabolic rate
– Retarded growth and sexual development
– Mental retardation (possibly)
• Hypothyroidism later in life
–
–
–
–
–
–
Decreased metabolic rate
Loss of mental & physical vigor
Weight gain
Loss of hair
Yellow discoloration of the skin
myxedema
Goiter
• Caused by lack of iodine in the diet
• Iodine is needed to synthesize thyroid
hormone
• Lack of iodine causes drop in thyroid
hormone production/secretion
• Negative feedback loop informs
hypothalamus and anterior pituitary to
release releasing hormones and TSH
• Lack of iodine causes enlargement of thyroid
gland
Calcitonin
• The 3rd hormone secreted from the thyroid
gland
• Target cells – bone
• Function – regulates calcium levels in the
blood by decreasing blood calcium levels
– Increases action of osteoblasts (build bone)
and inhibits action of osteoclasts (breakdown
bone)
– Antagonist to parathyroid hormone
Parathyroid Glands
• Parathyroid glands are embedded in the
posterior aspect of the thyroid glands
• Usually 4 or 5 parathyroid glands
Parathyroid Hormone
• Secreted from Parathyroid glands
• Target cells: bone and kidney
• Action: maintains calcium homeostasis
– Increases osteoclast activity; decrease
osteoblast activity
– Calcium absorbed in kidneys and returned to
the bloodstream
– Activates vitamin D in the kidneys which
increases intestinal absorption of calcium
• Parathyroid hormone is an antagonist to
calcitonin
Adrenal Glands
• Located on top of both of the kidneys
• Composed of two parts:
– Outer portion  adrenal cortex
– Inner portion  adrenal medulla
• Both parts of the adrenal glands are
structurally and functionally different; often
treated as two different glands
Adrenal Cortex
• Composed of three distinct layers or zones
– Outer zone  secrete mineralocorticoids
– Middle zone  secrete glucocorticoids
– Inner zone  secrete glucocorticoids and
gonadocorticoids
Mineralocorticoids
• Mineralocorticoids – regulate electrolytes in the
body
• In humans the most important mineralcorticoid is
aldosterone
• Target cell – kidneys
• Function – maintaining sodium homeostasis in the
blood
– In the kidneys, sodium ions are reabsorbed from the
urine back to the blood
– Sodium ions are exchanged for potassium or hydrogen
ions
– Aldoesterone also promotes water retention because reabsorption of sodium ions also causes water to be
reabsorbed
Regulation of Aldosterone Secretion
•
•
Aldosterone secretion is controlled by the reninangiotensin mechanism
This mechanism is a negative feedback loop that
helps maintain homeostasis of blood pressure
1. Blood pressure drops in the kidneys  renin (an
enzyme) is secreted
2. Renin converts angiotensinogen to angiotensin I
3. Angiotensin I travels to the lungs where enzymes split
the molecule forming angiotensin II
4. Angiotensin II travels to the kidneys where it simulates
the secretion of aldosterone
5. Aldosterone causes reabsorption of sodium ions 
followed by water reabsorption  increase in blood
pressure
Glucocorticoids
• Main glucocorticoid secreted from the
adrenal cortex is cortisol (also
hydrocortisone)
• Target cells – general; affect every cell in
the body
Cortisol - Functions
• Accelerate protein breakdown into amino
acids
– Amino acids travel to liver and are converted
to glucose (gluconeogenesis)
– Increased glucocorticoids (cortisol) 
increased breakdown of proteins in tissue
(tissue wasting)  hyperglycemia
• Shift cells from carbohydrate catabolism to
lipid catabolism for energy sources
– Further causes hyperglycemia
Cortisol – Functions cont…
• Help maintain blood pressure
– Permissiveness relationship with epinephrine
and norepinephrine
– Epi and NE cause vasoconstriction of blood
vessels
• Suppression of immune system responses
Glucocorticoid Hypersecretion
• Cushing Syndrome
– Too much cortisol is being secreted
– Causes:
• Could be caused by hypersecretion of ACTH from anterior
pituitary (tumor)
• Cirrhosis of liver or liver failure  can’t breakdown hormones
– Signs/Symptoms:
•
•
•
•
•
•
•
Abnormal hair growth
buffalo hump
muscle wasting
skin breakdown (thin skin)
striae across abdomen and thighs
truncal obesity
Susceptible to infection
Adrenal Insufficiency
• Hyposecretion of mineralcorticoids &
glucocorticoids  Addison Disease
• Signs/Symptoms:
– Drop in blood sodium
– Hypoglycemia
– Increase in blood potassium
– Dehydration
– Weight loss
Adrenal Medulla
• Secretes two nonsteroids in the
catecholamine class
– Epinephrine and norepinephrine
– Bind to sympathetic effectors and enhance
the effects of the “fight or flight” response of
the autonomic nervous system
Pancreas
• Located in the LUQ
• Contains both endocrine and exocrine
tissue
• Endocrine portion is made up of tiny
islands of cells called pancreatic islets
(also islets of Langerhans)
• Alpha cells secrete glucagon
• Beta cells secrete insulin
Pancreatic Hormones
• Glucagon
– Increases blood glucose levels
• Converts glycogen to glucose in liver cells
• Stimulates gluconeogenesis
– Target cells  liver
• Insulin
– Decreases blood glucose levels
• Promotes movement of glucose, amino acids, fatty acids into
cells
• Promotes metabolism of these molecules once by cells
– Target cells  general (all cells)
• Glucagon and Insulin produce antagonistic
effects (fig 16-27, page 512)
Diabetes
• Results from either
– 1) inadequate or absence of insulin
production
– 2) Insulin resistance – decreased insulin
receptors results in decreased effectiveness
of glucose uptake
Diabetes – Signs & Symptoms
• Hyperglycemia – elevated amounts of
glucose in the blood
– Results glucose not entering the cells properly
• Glycosuria – glucose present in the urine
– Elevated glucose levels in the blood exceeds
kidney’s abilities to reabsorb glucose; glucose
“spills over” into the urine
• Polyuria – increased urine production
– Water follows glucose lost in urine
Diabetes – Signs & Symptoms
• Polydipsia – excessive thirst
– Polyuria causes dehydration
• Polyphagia – excessive and continuous
hunger
– Although blood sugar is high cells are
“starving” because cells cannot uptake
glucose
**3 P’s = polyuria, polydipsia, polyphagia**
Diabetic Ketoacidosis
• Diabetics are unable to utilize glucose for energy –
cells must use protein and fat
• Large quantities of fat metabolism results in build
up of acidic metabolites called ketone bodies
• Signs/Symptoms
–
–
–
–
–
–
–
Acidosis
Abdominal pain
Nausea/vomiting
Fruity breath
Decreased LOC (levels of consciousness)
Coma
death
Type 1 Diabetes
• Absolute deficiency of insulin production
• Cause of beta cell destruction is unknown
• Requires insulin injections or an insulin
pump
Type 2 Diabetes
• Previously called non-insulin-dependent
diabetes (NIDDM) or adult onset diabetes
• Beta cell produce reduced amounts of
insulin
• Loss of insulin receptors on target cells
leads to insulin resistance
• Treated with insulin injections, oral
diabetic medication and lifestyle
modifications
Complications of Diabetes
Untreated or poorly controlled diabetes can
lead to many complications that affect
almost every system in the body:
• Atherosclerosis – build up of fatty
materials in the blood vessls
– Lead to heart attack, stroke, reduced
circulation
• Diabetic retinopathy – can lead to
blindless
Complications of Diabetes
• Neuropathy – nerve damage
– Amputations
• Kidney disease
– May require dialysis
Gonads – Testes & Ovaries
Testes:
• Composed mainly of coils of seminiferous tubules
& interstitial cells
• Interstitial cells secrete testosterone
• Target cells – general
• Function:
– Growth & maintenance of male sexual characteristics
– Sperm production
• Testosterone secretion is regulated by the
gonadotropin  leutinizing hormone (LH)
Gonads – Testes & Ovaries
Ovaries:
• Estrogen
– Secreted by cells of the ovarian follicles
– Target cells: general
– Functions:
• Promote development & maintenance of female
sexual characteristics
• Breast development
• Regulation of menstrual cycle
Gonads – Testes & Ovaries
Ovaries:
• Progesterone (“pregnancy-promoting
hormone”)
– Secreted by corpus luteum
– Target cells: general
– Functions (with estrogen):
• Maintains the lining of the uterus to maintain a
pregnancy
• Remember Estrogen & Progresterone
secretion is regulated by FSH and LH
(gonadotropic hormones)
Placenta
• Tissue that forms along the lining of the
uterus
• Serves as the connection between the
circulatory systems of the mother and
developing fetus
• Secretes human chorionic gonadotropin
(hCG)
• Target cells: ovaries
Placenta
• Function:
– Stimulates hormone (estrogen &
progesterone) secretion from the ovaries
– High levels of estrogen & progesterone help
maintain uterine lining for pregnancy
• hCG is high during the 1st trimester
• A high hCG level is used to confirm a
pregnancy