ENDOCRINE SYSTEM
CHAPTER 11
1
Overview of Endocrine System
and
Categories of Hormones
2
Endocrine System
ductless glands
• Endocrine glands are ________
hormones (biologically active regulatory molecules) into the
• Secrete _________
blood
______
receptor
• To exert an effect in a cell, a hormone must bind to a specific _________
protein for that hormone on a target cell
• The endocrine system is involved in homeostasis, such as: regulation of
3
metabolism, water & electrolyte balance, growth, & reproduction
Characteristics of Hydrophilic Hormones
• Amino acid-based hormones
hydrophilic
• Highly water soluble, polar: _________
cross plasma membrane (PM) of
• Cannot _____
target cell: hormone does ___
not enter cell
plasma membrane
• Receptor is in _________________:
hormone binds to outer surface
• Exception: melatonin
• Mechanism of action:
• Binding of hormone to receptor in PM
activates enzymes via 2nd messenger
system → activation of preexisting
proteins → metabolic effects
• Cannot
______ be taken orally (peptide hormones)
• digestive enzymes break them down;
taken by injection
• Transport in plasma: ____
free
• Exception: catecholamines are 50%
bound to albumin
4
Types of Hydrophilic Hormones
• Amines: modified amino acids derived from tyrosine & tryptophan
• Catecholamines: hormones secreted by the adrenal medulla (E &
tyrosine
NE) derived from amino acid _______
• Melatonin: derived from nonpolar tryptophan
• Synthesis: Enzymatically synthesized from precursor amino acid
• Peptide hormones: Polypeptides, Proteins, and Glycoproteins
< 100 amino acids; Proteins: __
• Polypeptides: __
> 100 amino acids
polypeptides
• Most hormones are __________
• Glycoproteins: protein bound to
carbohydrate groups
rough endoplasmic
• Synthesized by _____
reticulum (RER) of endocrine cells
• Stored in secretory vesicles in cytoplasm
until stimulated
exocytosis
• Secreted by _________
5
Characteristics of Lipophilic Hormones
• Highly ____
lipid soluble, non-polar:
hydrophobic
• Can pass through the plasma
membranes of cells
inside target cell
• Receptor is _____
• Mechanism of action:
• Binding of hormone to
receptor in cell → transcription
new proteins
→ synthesis of ____
→ alter cell activity
Can be taken orally: digestive
• ____
tract does not secrete enzymes
that destroys them
• Transport in blood: mostly
reversibly ______
bound to plasma
proteins called transport proteins
6
Types of Lipophilic Hormones
• Steroid Hormones
• Composed of 4 fused carbon rings
cholesterol & converted
• Synthesis: derived from _________
by enzymes to various steroid hormones
smooth endoplasmic reticulum
• Made in _______
• Not
___ stored, once formed, immediately diffuse out
• Secreted by diffusion
• Produced by gonads & placenta (estrogen, progesterone,
testosterone) and adrenal cortex (aldosterone, cortisol, DHEA)
• Thyroid hormones
• Hydrophobic amines
• Tetraiodothyronine or thyroxine (T4),
triiodothyronine (T3)
• Synthesis: made by thyroid follicular cells
from tyrosine + iodine
Stored in colloid of thyroid gland: ~3 months
• ______
diffusion
• Secreted by ________
7
Prohormones
Ex:
inactive precursors of peptide hormone
• Preprohormone & prohormone: large _______
peptide hormones initially made as preprohormone
• Synthesis: Many _______
pro
• Enzymes in RER: preprohormone → ____hormone
active hormone +
• Secretory vesicles: enzymes convert prohormone → ______
peptide fragments; stored in vesicles until stimulation
• Secretion upon stimulation: Active hormone + peptide fragments
prior to
within gland cell that synthesized it to active form _____
• Converted ______
secretion
• Ex: insulin synthesis
8
Prehormone
• Prehormones: inactive molecules secreted by
endocrine gland
target cell converts it to the active
• The ______
form of the hormone
• Endocrine cell secretes hormone as
inactive (e.g., T4)
_______
• Examples: vitamin D, testosterone, thyroid
hormone
9
Control of Hormones
10
What Affects Effective Plasma Concentration?
• Concentration of free (unbound) hormone depends on:
secretion
1. rate of hormone ________,
2. amount of hormone bound to carrier proteins,
liver kidneys, or target organs
3. rate of metabolic inactivation: by _____,
•
Half-life of a hormone: the time required for the plasma
reduced by half
concentration of a given amount of hormone to be _______
minutes
• Hydrophilic hormones: ________
• Lipophilic hormones: hours to days
• Physiological range: normal concentration of hormone; produces normal
response
high can produce abnormal
• Pharmacological concentrations (abnormally ____):
effects
• High concentrations may result in binding to receptors of related
hormones → can result in widespread side effects
• Examples: anabolic steroids, cortisol
11
Control of Hormone Secretion
1. Hormonal stimulation
another
• The binding of ________
tropic
hormone called a ______
hormone
• Tropic (trophic) hormones:
• Main function: regulate
hormone secretion of
_______
another endocrine gland
• Additional function: maintain
the structure (____)
size of the
endocrine target structures
• Example: TSH binds to thyroid
gland → stimulates
thyroid gland to secrete thyroid
___________
hormone
12
Control of Hormone Secretion
2. Humoral stimulation
ions or
• The concentration of ____
blood stimulate
nutrients in _____
gland to secrete its hormone
glucose
• Example: rise in _______
concentration in blood →
pancreas to secrete
stimulates ________
insulin
13
Control of Hormone Secretion
3. Neural stimulation
• Direct stimulation by the nervous
system:
neurons releasing
• ________
neurotransmitters on endocrine
gland
• Occurs via neuroendocrine
reflexes: reflexes that produce a
sudden increase in hormone
secretion in response to neuronal
stimulation
• Example: sympathetic neurons
stimulate adrenal medulla to secrete
Epinephrine (E) and
_____________
________________
Norepinephrine (NE)
14
Mechanisms Controlling Rate of Hormone Secretion
• Most hormonal regulatory systems work
via negative-feedback control
• When output of a system
__________
counteracts a change in the input
• The hormone itself regulates the
stimulus controlling its own secretion
• Example: sufficient T4, T4 inhibits:
responsiveness of the
• the ______________
anterior pituitary to TRH and
• the hypothalamus from
secreting TRH
________
• Some hormone secretion rates are also
circadian rhythms
regulated by diurnal or ________
• Secretion rates rhythmically fluctuate
up and down as a function of time (Ex:
cortisol secretion)
15
Hormone Interactions
16
Hormone Interactions
• Hormones can influence activity of another hormone:
• Synergistic: when the activity of
reinforces the
one hormone _________
activity of another hormone; effect
can be
• additive (acting together
_______
greater effect than alone)
• Example: E & NE
together stimulate a
greater increase in heart
rate
• or complementary (each
different aspect
produces a _______
of action)
• Example: Milk production
& secretion: requires
estrogen, cortisol,
prolactin, and oxytocin
17
Hormone Interactions
• Hormones can influence activity of another hormone:
• Permissiveness: when the presence
of one hormone is _______
required for
another hormone to exert its ___
full
effects
# of receptors for
• by increasing __
that hormone or by promoting
synthesis of an enzyme required
for hormone’s other effects
• Example: when thyroid hormone
is present, E stimulates much
more lipolysis than in its absence
____________
• Antagonism: when one hormone
________
opposes the effects of another
• Example: glucagon and insulin have antagonistic effects on liver
cells: Glucagon increases blood glucose levels; insulin decreases
blood glucose levels
18
Target Cells Alter # of Hormone Receptors
• Upregulation (priming effects):
Target cells _______
______
increase the number of
receptors for a hormone in response
to a prolonged lower than normal
concentration of the hormone
• Increases target cell’s
responsiveness to that hormone
_____________
• Ex: Anterior pituitary cells in
response to ↓ GnRH
• Downregulation: Target cells
decrease the number of ________
receptors
_________
for a hormone in response to a
high hormone levels
prolonged _____
• Decreases target cell responsiveness (desensitization) to that
hormone
• Ex: adipose cells in response to ↑ insulin
19
How hormones work:
Mechanisms of action of
Lipophilic Hormones
20
Steroid Hormone Mechanism of Action
• Transported in plasma attached to carrier proteins; unbinds to enter cell
through PM and bind to receptors __
• Diffuse _______
in cytoplasm or nucleus of
target cell (nuclear hormone receptors) → form a hormone-receptor
complex
• In nucleus hormone-receptor complex binds activates specific genes by
new proteins → cell
activating transcription → translation → synthesis of ____
21
response
Steroid Hormone Mechanism of Action
• Inside the nucleus, hormone-receptor
complex acts like a transcription factor by
binding to hormone response element
(HRE):
• short segment of ____
DNA near gene that
will be transcribed
• In order to activate or deactivate a gene,
dimerization is required
• 2 receptors each bound to a hormone
bind to the HRE forming a _____dimer
homo
• If transcription is activated → newly
synthesized protein → produces target
cell’s response
22
Thyroid Hormone Mechanism of Action
• Most (99.96%)
Thyroxine (T4)
travels in blood
attached to
carrier protein
• T3 & T4 unbinds
to enter target
cell
target cell, T4 converted to ___
• Inside the ______
T3
inside the nucleus ______
bound to
• Thyroid hormone receptor proteins are located ______
HRE, even in absence of hormone
• Dimerization is required to alter transcription
Hetero
• ______dimer:
one receptor binds T3 (Th receptor), other binds 9-cisretinoic acid (RXR receptor) – derivative of vitamin A
• Activated transcription → synthesis of new proteins → cellular response23
How hormones work:
Mechanisms of action of
Hydrophilic Hormones
24
Hydrophilic Hormones: Mechanism of Action
cross
• Hydrophilic hormones hormones cannot ______
PM of target cells; bind to outer surface of
receptor in PM of target cell
• Binding changes conformation of receptor →
initiates a series of biochemical events across
the membrane: signal transduction pathway
preexisting
• End result: Alters activity of ___________
intracellular proteins to produce effect
• Receptors: channel-linked, enzyme-linked, or
G-protein linked
________
• First messenger: hormone
intracellular
• Second messenger: __________
messenger produced by binding of
extracellular messenger to receptor
• Advantage of 2nd messenger system: signal
amplification: ability of small changes in
large
concentration of 1st messenger to cause _____
responses in target cell
25
Adenylate Cyclase cAMP 2nd Messenger System
1. Hormone binds to receptor
changing conformation of
receptor
2. G protein releases GDP &
binds GTP & becomes
________
activated
3. Alpha subunit dissociates &
activates adenylate cyclase:
catalyzes ATP → cAMP
second messenger):
4. cAMP (_______
activates a protein kinase:
enzyme that _____________
phosphorylates a
protein by transferring
phosphate group from ATP to it
5. Protein kinase phosphorylates
a protein → changes activity of
protein → cell response (6)
E & NE binding to
• Example: _______
beta adrenergic receptors
1st
2nd
messenger
26
Phospholipase C-Ca2+ 2nd Messenger System
1. Binding of hormone to
receptor activates __-protein
G
2. Alpha subunit dissociates &
phospholipase C
activates ______________
3. Phospholipase C catalyzes
conversion of membrane
phospholipid PIP2 → DAG
IP3
(diacylglycerol) and ___
(inositol triphosphate): 2nd
messengers
Ca2+
• 5b. IP3 diffuses into cytosol & binds to receptors in SER→ opens Ca2+
Ca2+ released into cytosol; Ca2+ either:
channels → ____
• 6b. Acts on proteins to stimulate contraction or secretion OR
calmodulin → activates
• 6c. Acts as a 2nd messenger by binding to __________
protein kinase → phosphorylates a protein → cell response
α1 adrenergic receptor
• Example: epinephrine (E) binding to ___
27
Signaling Pathways Involving Tyrosine Kinase
• Receptor tyrosine kinase: The receptor is also an
enzyme tyrosine kinase: phosphorylates
tyrosine residues
_______
1. Binding of hormone to receptor → change in
conformation of receptor → activates enzymatic
portion on cytoplasmic side of PM
2. Autophosphorylation of receptor: receptor
own tyrosine residues
phosphorylates its ____
3. Inactive protein binds to phosphorylated
enzyme receptor which phosphorylates it,
activating protein
4. Activates signaling pathways → cellular
response
insulin receptor is a tyrosine kinase
• Example: _______
• Cellular response: insertion of glucose
transporters into PM to allow facilitated
__________
diffusion of glucose: glucose uptake
28
Pituitary Gland and
Hypothalamus
Assigned Reading: Anterior & Posterior
Pituitary Hormones: pp. 330-332
The Pituitary Gland: Hypophysis
• Anterior pituitary = adenohypophysis
(adeno = ________)
glandular
• Formed embryonically from
________
epithelial tissue
• Synthesizes the hormones it
peptide hormones
releases: 6 _______
• All but prolactin are tropic: regulate
secretion of another hormone from
another endocrine gland
• Posterior pituitary = neurohypophysis
nerve
• Formed embryonically from ______
tissue
• Secretes 2 peptide hormones
controls release of
• Hypothalamus _______
hormones from both lobes
ADH, oxytocin
GH, TSH, ACTH,
Prolactin, FSH, LH
Anterior Pituitary Hormones
1. Growth Hormone (GH):
• Metabolic effects:
↑ blood fatty
• ↑ lipolysis: __
acids
• ↑ blood glucose levels
synthesis
• promotes protein ________
• Growth-promoting effects:
• stimulates liver to secrete
IGF-1 → _____
_____
bone growth
• GH & IGF-1 simulate protein
synthesis (↑ size of cells)
• Target tissues: adipose
tissue, skeletal muscles, liver,
soft tissues (bone &
cartilage)
IGF-1 & GH targets:
skeletal muscle
IGF-1 targets: bone
& cartilage
GH targets:
adipose,
skeletal muscle
liver
Anterior Pituitary Hormones
2. Thyroid Stimulating Hormone (TSH):
• Action: stimulates thyroid ______
gland to
produce & secrete thyroid hormones
________
• Target tissue: thyroid gland
3. Adrenocorticotropic hormone
(ACTH):
• Action: stimulates adrenal cortex to
secrete glucocorticoids (______)
cortisol
• Target tissue: adrenal cortex
4. Prolactin (PRL):
• Not tropic
production &
• Action: stimulates milk _________
secretion by mammary glands after
giving birth (in females)
• Target tissues: mammary glands
Anterior Pituitary Hormones
gonado
• FSH & LH: _______tropic
hormones
• Target tissue: gonads
5. Follicle-stimulating hormone
(FSH):
growth of
• In females: stimulates ______
follicles and estrogen secretion
• In males: promotes _____
sperm
production
6. Luteinizing Hormone (LH):
• In females:
• stimulates ovulation and
formation of corpus luteum
• regulates secretion of
estrogen and progesterone
testosterone
• In males: stimulates __________
secretion
Anterior Pituitary Hormones
(cortisol)
*
*See slide on GH for specific information
*
Hypothalamic Control of the Anterior Pituitary
• Secretion of anterior pituitary
hormones: controlled by
hormones secreted by the
hypothalamus
____________
• Hypothalamic hormones
produced by neurons in the
hypothalamus & secreted:
• into the hypothalamohypophyseal portal
system:
primary capillaries →
portal venules →
_____
secondary capillaries
• Hypothalamo-hypophyseal portal system: vascular system
composed of 2 ____________________
interconnected capillary beds that transports
hypothalamic hormones directly from hypothalamus to anterior pituitary
Hypothalamic Control of the Anterior Pituitary
• Most hypothalamic hormones are peptide hormones
• From the secondary capillaries they act on anterior pituitary cells:
stimulate the anterior pituitary to secrete its
• Releasing hormones ________
hormones
prevent the anterior pituitary from secreting
• Inhibiting hormones _______
its hormones
*
*Somatostatin also called: Growth hormone inhibiting hormone (GHIH)
Hypothalamic Control of Anterior Pituitary
Hypothalamic hormones:
CRH, GnRH, TRH, GHRH,
GHIH (somatostatin), PIH (dopamine)
Anterior Pituitary
hormones
Control of Anterior Pituitary Hormone Secretion
• Anterior pituitary hormone secretion is
regulated by the:
1. hypothalamus: via releasing & inhibiting
hormones
2. other _____
brain centers acting on
hypothalamus; examples:
• stress stimulates the hypothalamus to
secrete CRH
• Hypoglycemia, thyroid hormones,
testosterone, stimulate secretion of
GHRH
negative feedback inhibition
3. ________
• the anterior pituitary hormone inhibits
the secretion of its releasing hormone
hypothalamus e.g., growth
from the ____________:
hormone
• from the hormone secreted by its _____
target
gland: e.g., ACTH, TSH, FSH & LH
Feedback Control of the Anterior Pituitary
• Relationship between
hypothalamus, anterior pituitary,
axis
and target tissue is called an ____
• E.g.,: Hypothalamus-pituitarythyroid axis, Pituitary-gonad
axis, Pituitary-adrenal axis
• In negative feedback inhibition
from the hormone secreted by its
target gland, target gland hormone
can inhibit:
response of the anterior
• the _________
pituitary to releasing hormones
• the hypothalamus from
secreting releasing hormone
________
Hypothalamus-pituitary-thyroid axis
Example of Negative Feedback Inhibition
• High levels of estrogens and
testosterone inhibit:
ability of the anterior
• the ______
pituitary to secrete FSH and
in response to GnRH
LH ___________
stimulation
secretion of GnRH
• The _________
from the hypothalamus
Hypothalamus-pituitary-gonad axis
Posterior Pituitary & Hypothalamus
• Posterior pituitary (Neurohypophysis): stores & releases hormones
NOT synthesize hormones
• Does _____
• ADH & oxytocin (peptide hormones) are:
• synthesized in cell bodies of neurosecretory cells of the supraoptic
hypothalamus
and paraventricular nuclei of the _____________,
tract
• transported along axons of the hypothalamo-hypophyseal _____,
stored in axon terminals in posterior pituitary
• ______
Hormones Released From Posterior Pituitary
• Antidiuretic hormone (ADH;
arginine vasopressin)
• Actions:
• Main action: promotes water
reabsorption by kidneys
___________
• Vasoconstriction
_____________ of arterioles
• Target tissues: kidneys &
arterioles
• Oxytocin
• Actions:
• In females: Stimulates
___________
contractions of the uterus
during labor & milk ________
ejection
during breast-feeding
Bonding hormone
• “________”
• Target tissues: mammary glands & uterus
Control of Secretion of Posterior Pituitary Hormones
• Release of ADH and oxytocin is
controlled by neuroendocrine
reflexes
• When stimulus excites
action potentials
hypothalamus, _______________
trigger exocytosis & release of
hormone into blood
• Stimulus for ADH:
↑ in blood ________
osmolality &
• ___
↓ in blood _______
volume
• ___
• Stimulus for Oxytocin
stretching of
• During labor: ________
cervix of uterus
• After labor: baby suckling
Adrenal Glands
The Adrenal Glands
• Adrenal medulla (inner):
neural
• Derived from embryonic ______
tissue
• Hormones secreted in response to
stimulation by sympathetic
preganglionic neurons (in response
to stress and exercise)
E
• Secretes catecholamines: __
(80%) & NE (20%):
• Enhance fight-or-flight response:
↑ HR, cardiac output, & BP
• __
• Increase mental alertness
• Dilate airways
↑ blood flow to heart, liver, skeletal muscle, and adipose
• __
↑ blood levels of glucose and fatty acids
• __
The Adrenal Glands
• Adrenal cortex (outer):
glandular
• derived from embryonic _________
epithelium
steroid hormones
• secretes _______
(corticosteroids) in response to
hormonal stimulation
• Mineralocorticoids from zona
glomerulosa regulate Na+ and
__________:
aldosterone
K+ balance; e.g., ___________
• Glucocorticoids mainly from
zona fasciculata regulate
glucose metabolism; e.g.,
cortisol
________
• Adrenal androgens
• Mainly from zona reticularis
• weak androgens (masculinizing sex hormones): e.g., DHEA: in
females promote libido & are converted to estrogens
Adrenal Cortex Hormones
• Aldosterone: Most significant
mineralocorticoid
• Actions: promotes kidney
Na+ (and as a
reabsorption of ___
result water) and secretion of K+
increase blood
• helps _______
volume and pressure
• is secreted in response to:
• high plasma K+ levels or
• angiotensin II (RAAS) as a
result of low
___ Na+, ECF
blood pressure
volume, or _____
• Secretion is independent of
anterior pituitary control
Adrenal Cortex Hormones
• Cortisol: most abundant glucocorticoid
• Actions:
↑ blood aa’s)
• ↑ protein degradation (__
↑ blood glucose)
• ↑ gluconeogenesis (__
↑ blood fatty acids
• ↑ lipolysis: __
• Resistance to stress
• Anti-inflammatory & immunosuppressive
effects
• Exogenous glucocorticoids (e.g., prednisolone,
hydrocortisone): immunosuppressive & antiinflammatory effects; long-term use may cause:
Hyperglycemia & ↓ glucose tolerance
• _____________
• ↓ synthesis of collagen
breakdown osteoporosis
• ↑ bone resorption (__________):
Regulation of Cortisol Secretion
Cortisol secretion is regulated by:
• negative feedback - maintains
cortisol levels around a set point
• Secretion is stimulated by
ACTH
_____
• High levels of cortisol inhibit
the anterior pituitary from
responding to CRH and the
_________
hypothalamus from
secreting CRH
________
• Diurnal rhythm: highest in the
morning lowest at night
_______,
increased
• Stress: results in _________
cortisol secretion
Cushing’s Syndrome: Cortisol Hypersecretion
high levels of
• Results from chronically ____
glucocorticoids
• Causes:
• Long-term high dose use of
glucocorticoid medication
• Pituitary tumor that secretes
ACTH
excessive ______
• Adrenal tumor that secretes
excessive cortisol independent of
ACTH
• Main Symptoms
Hyperglycemia and glucosuria
• ____________
(adrenal diabetes)
• Abnormal fat distribution
• “buffalo hump” & “moon face”
& abdomen
Stress Response: General Adaptation Syndrome (GAS)
• Stress response (GAS): generalized nonspecific response of body to
factor that threatens body’s ability to maintain homeostasis (stressor)
1. Alarm Reaction
• Goal: make energy sources
available for immediate physical
activity
sympathetic
• Activation of ___________
division of ANS: fight-or-flight
↑ blood glucose & fatty acids
• __
↑ blood volume & BP: (RAAS &
• __
ADH)
2. Resistance:
• Goal: to help body continue
fighting a stressor after fight-orflight ends
cortisol 3. Exhaustion: If resistance fails to
• Activation of CRH-ACTH-______
system: ↑ blood glucose, amino
combat stressor
acids, & fatty acids
• Body resources are depleted
Thyroid Gland
Thyroid Gland
• Largest purely endocrine gland
• Microscopic Anatomy:
• Follicle: spherical hollow sacs made up of:
synthesize & secrete
• Follicular cells: simple cuboidal epithelium; _________
T3 & T4
thyroid hormones (_______)
stores T3 & T4
• Colloid: protein rich fluid in lumen of follicle – _____
• Parafollicular cells (C cells): cells in between follicles
• Secrete _________
calcitonin (peptide hormone)
• Action of calcitonin: Inhibits activity of osteoclasts and stimulates
urinary excretion of calcium from kidneys → ↓ blood calcium levels
Synthesis of Thyroid Hormone
iodine and
• Thyroid hormones made from ______
tyrosine
_______
1.Iodine from diet is absorbed as
Iodide (I-) & actively taken from
blood → follicular cells → colloid
2.Thyroglobulin (TGB): synthesized in follicular
cells → colloid
3.I- oxidized &
attached to
tyrosine within
_______
TGB in colloid
MIT: I + tyrosine
DIT: 2I + tyrosine
iodines + 2 _______
tyrosine = Triiodothyronine (T3)
• MIT + DIT = 3 ______
• DIT + DIT = 4 iodines + 2 tyrosine = Tetraiodothyronine, thyroxine (T4)
Synthesis of Thyroid Hormone
•
4.
5.
6.
•
Thyroid hormones stored
in colloid ~100 days
When stimulated by
TSH, follicular cells take
in portion of colloid by
pinocytosis
___________
Droplets of colloid merge
with lysosomes; digestive
enzymes cleave off T3 &
T4 from ____
TGB
T3 & T4 diffuse through
PM into blood
Most T3 & T4 transported in
transport
blood attached to ________
protein: thyroxine-binding globulin
Actions of Thyroid Hormone
• Target tissues: most cells of body
1. Increases basal metabolic rate
• BMR = rate of energy expenditure at rest
Increases rate of cellular metabolism of
• _________
carbohydrates, lipids, & proteins
heat production;
• Calorigenic effect – increased ____
important role in maintaining normal body
temperature
2. Sympathomimetic effect
catecholamines (E, NE):
• Enhances actions of _____________
permissive effects – upregulate beta adrenergic
receptors
3. Regulate development & growth of nervous
tissue and bones
CNS
• Necessary for development of ____
• Acts synergistically with growth hormone to
stimulate ____
bone growth
• Required for GH synthesis and secretion
Control of Thyroid Hormone Secretion
•
•
•
•
Regulated by negativefeedback loop of the
hypothalamus-pituitary-thyroid
axis
____
Low levels of blood T3 & T4 or
low metabolic rate stimulate
hypothalamus to release ____
TRH
Thyroid Stimulating Hormone
(TSH): stimulates thyroid
synthesis and
hormone ________
secretion and maintains the
size of the thyroid gland
High levels of T3 & T4 inhibit
the anterior pituitary’s
response to TRH and the
________
hypothalamus from secreting
TRH
Hypothyroidism vs. Hyperthyroidism
• Excessive thyroid hormone
• Deficient thyroid hormone
• Causes
• Causes
• Graves’ disease
• failure of thyroid gland,
• Hypersecreting thyroid tumor
• deficiency of TSH or TRH
• Excess TRH or TSH
• Inadequate dietary iodine
• Symptoms
• Symptoms
• High BMR, weight loss, excessive
Low BMR, weight gain and
• ____
sweating, poor tolerance of ____,
heat
fatigue, poor tolerance of
↑ HR, palpitations,
weakness, __
cold slow weak pulse, slow
____,
excessive mental alertness,
mental responsiveness,
irritability, anxiety, emotional
Myxedema: edema that
causes puffy appearance of • Treatment
face, hands, & feet
• Drugs that interfere with thyroid
hormone synthesis
• Treatment
• Removing a portion of thyroid
• Replacement thyroid pills
gland
• Dietary iodine
• Radioactive iodine
• Goiter: enlarged
_______ thyroid
gland
• May accompany
hypothyroidism and
hyperthyroidism
• Occurs when thyroid
gland is excessively
stimulated
hypo
• In _____thyroidism,
goiter caused by thyroid
gland failure or lack of
iodine
_____
Lack of negative
• _____
feedback inhibition →
abnormally high levels
of TSH → stimulates
growth of thyroid
• endemic goiter
Goiter
Graves’ Disease
• Most common cause of
hyperthyroidism
• Autoimmune disease
• Body erroneously produces an
antibody that binds to TSH receptors
_______
on thyroid gland follicular cells
• Antibody: thyroid-stimulating
immunoglobulin (TSI)
• Stimulates secretion of thyroid
hormone and growth of thyroid
TSH
gland: acts like ____
negative
• Not subject to ________
feedback inhibition
• Characterized by exophthalmos:
bulging eyes
Concept Check
1. For each of the following conditions, determine if it
would cause a goiter and discuss why.
A. Deficiency of TSH
B. Failure of thyroid gland
C. Excessive TSH secretion
from a pituitary tumor
D. Graves’ Disease
E. From thyroid tumor
causing overactivity of
thyroid gland
Parathyroid Glands
Parathyroid Glands
(Chief)
(Oxyphil)
• Four rice-grain sized glands on posterior surfaces of thyroid gland
• Secrete parathyroid hormone (PTH):
• Peptide hormone
↑ [Ca2+] plasma
• Overall action: __
calcium concentration
• Most important hormone regulating plasma _______
• Target tissues: bones, kidneys, and intestine (indirectly)
PTH: Actions and Regulation of Secretion
• Actions of PTH:
• on bone: ↑ osteoclast activity:
↑ Ca2+
↑ bone resorption → __
levels in blood
• on kidneys:
↑ reabsorption of Ca2+ →
• __
↓ Ca2+urinary excretion
__
• Promotes formation of
active form of vitamin D
absorption
(calcitriol) → ↑ _________
of dietary Ca2+ from small
intestine
• Regulation of PTH secretion:
• plasma [Ca2+] via a negative feedback loop
Low blood [Ca2+] stimulates secretion of PTH
• ____
• High blood [Ca2+] inhibits secretion
Pancreas
Pancreas
• Pancreas is an exocrine and endocrine gland
• Exocrine cells are ______
acinar cells
islets of Langerhans):
• Endocrine cells are in pancreatic islets (_____
increases blood glucose
• Alpha cells: secrete glucagon: _________
decreases blood glucose
• Beta cells: secrete insulin: _________
• Delta (D) cells: secrete somatostatin (GHIH)
• Gamma (F) cells: secrete pancreatic polypeptide
Insulin Actions
Insulin primary target
tissues: resting skeletal
muscles, adipose, liver
• Insulin Actions:
Lowers blood glucose: by ↑ glucose
• _______
______
uptake and ↑ glycogenesis (synthesis of
glycogen from glucose)
________
• ↑ amino acid uptake and ↑ protein
synthesis
_________
• ↑ lipogenesis: formation of
triglycerides
___________ from fatty acids & glycerol
• Mechanism of insulin’s action of ↑ glucose
uptake:
• Insulin binds to its receptor → tyrosine
kinase signaling pathway → GLUT-4
inserted in PM → facilitated diffusion
of glucose into cell
Glucagon Actions
• Glucagon primary target tissues:
liver (mainly) & adipose
• Glucagon Actions:
Increases blood glucose
• _________
• ↑ Glycogenolysis:
breakdown of glycogen
_________
into glucose
• ↑ Gluconeogenesis:
formation of glucose from
noncarbohydrate
molecules
• ↑ Ketogenesis: formation of
ketone bodies from fatty acids
↑ Lipolysis: breakdown of
• __
triglycerides into fatty acids &
glycerol
Regulation of Insulin & Glucagon Secretion
• Mainly by plasma concentration of
glucose via negative feedback:
↑ blood glucose stimulates
• __
pancreatic ____
beta cells to secrete
insulin and inhibits pancreatic
alpha cells from secreting
glucagon
↓ blood glucose stimulates
• __
pancreatic _____
alpha cells to
secrete glucagon & inhibits
pancreatic beta cells from
secreting insulin
Diabetes Mellitus
• Diabetes = “siphon”; mellitus – sweet: Endocrine disorder characterized
by chronic high blood glucose (hyperglycemia)
secretion or _______
inability of insulin to stimulate
• from inadequate insulin ________
cellular uptake of glucose from blood
• Symptoms: glucosuria, ketones in urine, frequent urination of large
volume
• Long term consequences: cardiovascular disease, blindness, amputation
• Type I: insulin-dependent (juvenile-onset); autoimmune disease,
lack of insulin secretion
• Destruction of beta cells → ____
• Treatment: insulin injections
• Type II: noninsulin-dependent (adult-onset); ~95% diabetics; linked to
obesity
• Pancreas does not produce enough insulin and insulin resistance
_________:
↓ target cell sensitivity (________)
response to insulin
__
• Treatment: diet & exercise, drugs that improve cell sensitivity to
glucose or that stimulate the pancreas to secrete insulin, may need
insulin injection
Oral Glucose Tolerance Test
• Measure of the ability of beta cells to
ability of insulin to
secrete insulin and of the _____
lower blood glucose
• Patient drinks glucose solution and blood
samples taken over time
• Normal: rise in blood glucose reverses to
normal within 2 hours
• <100
____ mg/dl fasting plasma glucose
• Prediabetics:
• Impaired glucose tolerance: repeatable
fasting plasma glucose level of 100-125
mg/dl
• Higher insulin secretion due to insulin
resistance
• Diabetics: repeatable fasting plasma
>125 mg/dl
glucose _____
Glycated Hemoglobin (Hemoglobin A1c) Test
• Most common test to diagnose diabetes
• Glycated (glycosylated) hemoglobin: hemoglobin
becomes ______
______ the more plasma
bound to glucose
glucose there is for the life of the RBC (~120
days)
• Hemoglobin A1c test measures % of RBCs that
have sugar coated hemoglobin
• Reflects average blood glucose levels over
3 months
___
• A1c levels:
• Normal: <5.7%
• Prediabetes: 5.7-6.4%
• Diabetes: ≥ 6.5%
Source:
https://my.clevelandclinic.org/health/diagnostics/9731-a1c
Other Glands
Assigned Reading:
Pineal Gland: pp. 346-347
Thymus: Table 11.1 and slide on Thymus
Pineal Gland
• Pineal gland: small gland on roof of third ventricle in brain
melatonin amine hormone derived from tryptophan
• Secretes _________:
• Melatonin Actions: Helps regulate ________
circadian rhythm, believed to
promote sleep, suggested role in onset of puberty
SCN master
• Pineal gland regulated by suprachiasmatic nucleus (____):
biological clock located in ____________
hypothalamus
• Secreted in response to visual input from eyes
• During sleep, melatonin levels increase
Thymus
• Bilobed organ on superoanterior aspect of heart
• Large in infants, grows until puberty, then regresses
• Secretes ______
thymic hormones: thymosin, thymulin, & thymopoietin
T lymphocytes
• Action: Promote maturation of ____________
Paracrines and Autocrines
Paracrines and Autocrines
locally
• Paracrines: _____
acting regulatory
molecules produced by
one cell type that acts
on a _______
different cell type
tissue in
(different _____)
same organ
_____
• Autocrines: locally
acting regulatory
molecules that act on
same cell that
the _____
secretes them
Paracrines and Autocrines
• Eicosanoids: family of molecules
synthesized from a 20-C fatty acid from PM
____________:
phospholipids arachidonic acid
• Converted to leukotrienes & prostaglandins
• Prostaglandins: have a 5-sided carbon ring
in backbone; most diverse group of
paracrines & autocrines in most body cells
• Roles in: ___________,
inflammation reproduction,
constriction and dilation of blood vessels
& bronchioles, clotting, inhibit gastric
secretions
• SAIDs (steroidal anti-inflammatory drugs):
inhibit inflammation by inhibiting ________
synthesis of
eicosanoids
• NSAIDs (nonsteroidal anti-inflammatory
drugs): inhibit inflammation by blocking
action of cyclooxygenase (COX)
______