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Chapter 11
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I. Endocrine Glands and
Hormones
A.
Endocrine Glands
1. Ductless
2. Secrete hormones into the blood
3. Hormones are carried to target cells having
receptors for those hormones.
4. Many organs secrete hormones other than those
discussed in this chapter such as the heart, liver,
kidneys, and adipose tissue.
5. Neurohormones are secreted by specialized cells
of the hypothalamus
6. Hormones help regulate body metabolism,
growth, and reproduction
Major Endocrine Glands
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Pineal gland
Pituitary
gland
Hypothalamus
Thyroid gland
Adrenal gland
Pancreas
Pancreatic islet
(of Langerhans)
Ovary
Testis
(a)
(b)
b: © Ed Reschke
Partial Listing of Endocrine Glands
B.
Chemical Classification of Hormones
1. Amines, derived from tyrosine and tryptophan
a. Examples: hormones from the adrenal
medulla, thyroid, and pineal glands
2. Polypeptides and proteins
a. Examples: antidiuretic hormone, insulin, and
growth hormone
Chemical Classification of Hormones, cont
3. Glycoproteins are long polypeptides bound to a
carbohydrate.
a. Examples: follicle-stimulating and luteinizing
hormones
4. Steroids are lipids derived from cholesterol
a. Examples: testosterone, estradiol,
progesterone, cortisol
b. Secreted by adrenal cortex and gonads
Polypeptide & Glycoprotein Hormones
C.
Hormone Classifications by action
1. Polar hormones: water soluble
a. Cannot pass through plasma membranes
b. Must be injected if used as a drug
c. Includes polypeptides, glycoproteins,
catecholamines, norepinephrine, and epinephrine
2. Nonpolar: insoluble in water
1. Often called lipophilic hormones
2. Can enter target cells directly
3. Include steroids, thyroid hormone, and melatonin
4. Can be taken orally in pill form
D.
Prohormones and Prehormones
1. Prohormones are inactive hormones that must
be cut and spliced together to be active.
a. Example: insulin
2. Prehormones are inactive prohormones that
must be modified within their target cells.
Prohormones and Prehormones
E.
Common Aspects of Neural & Endocrine
Regulation
1. Hormones and neurotransmitters both interact
with specific receptors.
2. Binding to a receptor causes a change within the
cell.
3. There are mechanisms to turn off target cell
activity; the signal is either removed or inactivated.
4. Neurotransmitters and hormones have many
similarities
5. Some hormones can also be neurotransmitters in
the CNS
II. Mechanisms of Hormone
Action
Introduction
1. Hormones bind to receptors on or in target cells.
a. Binding is highly specific.
b. Hormones bind to receptors with a high affinity.
c. Hormones bind to receptors with a low
capacity; saturating the receptors with hormone
molecules
2. Lipophilic hormone receptors are in the cytoplasm
or nucleus
3. Water-soluble hormone receptors are on the outer
surface of the plasma membrane
Thyroid Hormone Action
1. Thyroxine (T4) travels to target cells on thyroxinebinding globulin (TBG).
2. Some T3 is also released, but is not bonded to a
carrier; “free iodine”
3. Inside the target cell, T4 is converted to T3.
4. Receptor proteins are located inside the nucleus
bound to DNA.
Thyroid Hormone Action
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Cytoplasm
Nucleus
DNA
4
Receptor
protein
mRNA
T4
mRNA
Carrier
protein
(TBG)
3
1
Binding
protein
6
Protein
synthesis
7
Thyroid
hormone
response
2
T4
Blood
5
T4
Target cell
Thyroid Hormone Action, cont
5. The hormone response element on the DNA has
two half-sites, one for a T3 receptor and one for a
9-cis-retinoic acid receptor (a Vit A derivative).
6. Binding of these molecules forms a heterodimer
because there are two different receptors
7. The binding of T3 will cause corepressor proteins
to be removed and coactivator proteins to be
recruited.
8. Vitamin D action in the cell is similar.
Thyroid Hormone Action
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RXR receptor
(for 9-cisretinoic acid)
TR receptor
(for
triiodothyronine)
Dimerization
T3
9-cis-retinoic
acid
Triiodothyronine
DNA
Hormoneresponse
element
Genetic
transcription
mRNA
Tyrosine Kinase System
a. Insulin and growth factors uses this system
b. The receptor is also the enzyme tyrosine kinase.
c. The ligand-binding site is on the outside of the
cell, and the enzyme faces the cytoplasm.
d. The enzyme portion is activated via
phosphorylation.
e. The activated receptor phosphorylates insulin
receptor substrate molecules.
f. This activates a cascade of enzymatic activity.
Tyrosine Kinase System
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Extracellular
fluid
Insulin
Alpha
Beta
P
ADP
P
P
P
ADP
ATP
Cytoplasm
ATP
Insulin
receptor
ATP
P
1. Binding of insulin to
receptor proteins
2. Phosphorylation of
receptor
ADP
3. Phosphorylation of
signal molecules
Cascade of effects
Tyrosine kinase now
active
Glucose uptake and
anabolic reactions
(a)
(b)
(c)
III. Pituitary Gland
A.
Introduction
1. The pituitary gland is attached to the
hypothalamus by the infundibulum
2. Divided into an anterior lobe (adenohypophysis)
and a posterior lobe (neurohypophysis)
a. The anterior pituitary is glandular epithelium
with two parts – pars distalis and pars tuberalis
b. The posterior pituitary is nervous tissue and
also called the pars nervosa
Pituitary Gland
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Hypothalamus
Optic chiasma
Anterior lobe
(adenohypophysis):
Infundibulum
Pars tuberalis
Pars distalis
Pars
intermedia
(fetus only)
Posterior lobe
(neurohypophysis)
B.
Pituitary Hormones
1. Secreted by the anterior lobe
2. Trophic hormones stimulate hormone secretion in
other glands:
a. Growth hormone (GH)
b. Thyroid-stimulating hormone (TSH)
c. Adrenocorticotropic hormone (ACTH)
d. Follicle-stimulating hormone (FSH)
e. Luteinizing hormone (LH) – in the male, it is
interstitial cell stimulating hormone (ICSH)
f. Prolactin (PRL)
Anterior Pituitary Hormones
Anterior Pituitary Hormones
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Paraventricular nucleus
Hypothalamus
Supraoptic nucleus
Median eminence
Portal system
Infundibulum
Posterior pituitary
Anterior pituitary
TSH
Prolactin
Thyroid
Mammary gland
ACTH
Adrenal cortex
Growth
hormone
FSH
Gonadotropins
LH
Bone
Muscle
Adipose
tissue
Ovary
Testis
3.
Posterior Pituitary Hormones
a. Stores and releases two hormones made in the
hypothalamus:
1) Antidiuretic hormone (ADH), which promotes
the retention of water in the kidneys (also
called arginine vasopressin – AVP)
2) Oxytocin, which stimulates contractions in
childbirth and milk let-down in lactation
C.
Hypothalamic Control of the Posterior Pituitary
1. ADH and oxytocin are produced by the
supraoptic and paraventricular nuclei of the
hypothalamus, respectively
2. They are transported along axons of the
hypothalamo-hypophyseal tract to the posterior
pituitary where they are stored.
3. Release is controlled by neuroendocrine reflexes.
a. ADH is stimulated by an increase in blood
osmolality
b. Oxytocin is stimulated by suckling
Hypothalamic Control of the Posterior Pituitary
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Paraventricular
nucleus
ADH and oxytocin
produced here
Supraoptic
nucleus
Hypothalamus
Optic chiasma
Infundibulum
Hypothalamohypophyseal
tract
Posterior pituitary
Anterior
pituitary
ADH and
oxytocin
released
D.
Hypothalamic Control of the Anterior Pituitary
1. The anterior pituitary
is controlled via
releasing and
inhibiting hormones
transported through
the hypothalamohypophyseal portal
system.
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Cell body
Axons to primary
capillaries
Median
eminence
Primary
capillaries
Portal venules
Pituitary stalk
Releasing
hormones
Posterior pituitary
Secondary
capillaries
Anterior
pituitary
Anterior
pituitary
hormones
Hypothalamic Control of Anterior Pituitary, cont
2. Releasing and inhibiting hormones
a. Corticotropin-releasing hormone (CRH)
b. Gonadotropin-releasing hormone (GRH)
c. Prolactin-inhibiting hormone (PIH) (dopamine)
d. Somatostatin
e. Thyrotropin-releasing hormone (TRH)
f. Growth hormone−releasing hormone (GHRH)
Hypothalamic Control of Anterior Pituitary
E.
Feedback control of the anterior pituitary
1. The final product regulates secretion of pituitary
hormones – negative feedback inhibition
2. The relationship between the hypothalamus,
anterior pituitary,, and the target tissue is called an
axis
3. Inhibition can occur at the pituitary gland level,
inhibiting response to hypothalamic hormones.
4. Inhibition can occur at the hypothalamus level,
inhibiting secretion of releasing hormones.
Feedback Control of the Anterior Pituitary
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Sensor
Integrating center
Effector
Hypothalamus
–
Thyrotropinreleasing
hormone
(TRH)
Anterior
pituitary
Thyroidstimulating
hormone
(TSH)
Growth
of thyroid
Thyroid
Inhibits
secretion
of TRH
–
Inhibits
responsiveness
to TRH
Thyroxine
Feedback Control of the Anterior Pituitary
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Sensor
Integrating center
Effector
–
Hypothalamus
Gonadotropinreleasing hormone
(GnRH)
Negative
feedback
Anterior
pituitary
–
Negative
feedback
Inhibits
secretion
of GnRH
Gonadotropins
(FSH and LH)
Gonads
Sex steroid
hormones
(estrogens and
androgens)
Inhibits
responsiveness
to
GnRH
F.
Higher Brain Controls
1. Since the hypothalamus receives input from
higher brain regions, emotions can alter hormone
secretion.
a. At least 26 brain regions and olfactory neurons
send axons to the GnRH-producing neurons.
b. Stressors increase CRH production as part of
the pituitary-adrenal axis
c. Circadian rhythms
IV. Adrenal Glands
A.
Structure of the Adrenal Glands
1. Found atop the kidneys
2. Consist of an outer adrenal cortex and an inner
adrenal medulla that function as separate glands
a. The adrenal medulla is neural tissue and
secretes epinephrine and norepinephrine in
response to sympathetic neural stimulation.
b. The adrenal cortex is glandular epithelium and
secretes steroid hormones in response to
ACTH; three layers – zona glomerulosa, zona
fasciculata, and zona reticularis
Adrenal Glands
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Adrenal gland
Kidney
Adrenal
cortex
Adrenal
medulla
Zona glomerulosa
Zona fasciculata
Conective
tissue
capsule
Adrenal
cortex
Zona reticularis
Adrenal
medulla
B.
Functions of the adrenal cortex
1. Secretes hormones made from cholesterol; called
corticoseroids or corticoids
2. Three categories:
a. Mineralocorticoids from the zona glomerulosa
regulate Na+ and K+ balance.
1) Example: aldosterone
b. Glucocorticoids from the zona fasciculata
regulate glucose metabolism.
1) Example: cortisol
c. Adrenal androgens from the zona reticularis
are weak sex hormones that supplement those
made in the gonads. Ex - DHEA
3.
Functions of cortisol (hydrocortisone)
a. Stimulates protein degradation
b. Stimulates gluconeogenesis and inhibits
glucose utilization to raise blood glucose levels
c. Stimulates lipolysis
4. Exogenous glucocorticoids are used medically to
suppress immune response and inhibit
inflammation; can have many negative side
effects
Steroid Hormones of the Adrenal Cortex
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Zona glomerulosa
Cholesterol
Zona fasciculata and zona reticularis
Cholesterol
Pregnenolone
Pregnenolone
17-Hydroxypregnenolone
Progesterone
Progesterone
17-Hydroxyprogesterone
Androstenedione
Deoxycorticosterone
Deoxycortisol
Other androgens
Deoxycorticosterone
Corticosterone
Corticosterone
Dehydroepiandrosterone
(DHEA)
Cortisol
Aldosterone
Mineralocorticoids
Glucocorticoids
Sex steroids
C.
Functions of the Adrenal Medulla
1. Epinephrine and norepinephrine
a. Activated with sympathetic response
b. Have effects similar to sympathetic innervation
but lasting 10 times longer
c. Increase cardiac output, respiratory rate, and
mental alertness; dilate coronary blood vessels;
elevate metabolic rates
2.
Stress and the Adrenal Gland
a. Stress increases secretion of ACTH, which results
in increased glucocorticoid release.
b. The stress hormones are glucocorticoids,
epinephrine, and CRH
c. Called the general adaptation syndrome (GAS).
1) Good for proper recovery after stress, such as
an illness or trauma.
2) Cortisol helps inhibit the immune system so it
does not overrespond.
Stress and the Adrenal Gland, cont
d. Chronic stress leads to an increased risk of
illness.
1) Cortisol may act on higher brain regions,
contributing to depression and anxiety and
memory.
2) By stimulating the liver to release glucose,
insulin receptors may become resistant,
making it harder to treat people with
diabetes.
e.
Stages of GAS
1) Alarm reaction – activates the adrenal glands
2) Stage of resistance – readjustments in
response
3) Stage of exhaustion – may lead to sickness or
death
f. GAS effects
1) Stimulates growth of adrenal glands
2) Atrophy of lymphatic tissue of spleen, lymph
nodes, and thymus
3) Formation of bleeding peptic ulcers
Activation of pituitary-adrenal axis by nonspecific
stress
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Sensor
Integrating center
Effector
Nonspecific stress
Higher
brain centers
–
Hypothalamus
CRH
Negative
feedback
–
Cortisol
Adrenal
cortex
Anterior
pituitary
ACTH
V. Thyroid and Parathyroid
Glands
A.
Thyroid Gland Structure
1. Located just below the
larynx
2. Has two lobes on
either side of the
trachea, connected by
the isthmus
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Thyroid
cartilage
of larynx
Cricoid
cartilage
of larynx
Thyroid
gland
Trachea
3.
Microscopic Thyroid Gland Structure
a. Consists of hollow spaces called thyroid follicles
lined with simple cuboidal epithelium composed
of follicular cells that produce thyroxine
1. Interior of the follicles is filled with a fluid called
colloid.
2. Outside of the follicles are parafollicular cells that
secrete calcitonin
Photomicrograph of the Thyroid Gland
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Follicular
cells
Follicles
Colloid
© Ed Reschke
B.
Production & Action of Thyroid Hormone
1. Thyroglobulin is made by the follicular cells.
a. Thyroid follicles actively accumulate iodide (I-)
and secrete it into the colloid.
b. The iodine is attached to tyrosines within the
thyroglobulin molecule.
1) One iodine produces monoiodotyrosine
(MIT).
2) Two iodines produce diiodotyrosine (DIT).
Production & Action of Thyroid Hormone, cont
c. Enzymes within the colloid attach MIT and DIT
together:
1) DIT + DIT = T4 (tetraiodothyronine or thyroxine)
2) DIT + MIT = T3 (triiodothyronine)
d. These are still bound to thyroglobulin.
1) They dissociate from thyroglobulin when the
thyroid gland is stimulated by TSH.
2) Secreted into the blood
Production & Storage of Thyroid Hormone
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Blood plasma
Thyroid
uptake of
iodide
Thyroid follicle
I–
(Iodide in
plasma)
I–
Peroxidase
H2O2
Oxidized
iodide
+
Thyroglobulin
Monoiodotyrosine
(MIT)
Diiodotyrosine
(DIT)
MIT + DIT
Colloid
DIT + DIT
Triiodothyronine
(T4)
Tetraiodothyronine
(T4)
Bound to
thyroglobulin
Plasma
carrier
protein
Thyroid
hormone
secretion
T3
T4
2.
a.
b.
c.
d.
Action of Thyroid Hormone
Stimulates protein synthesis
Promotes maturation of the nervous system
Increases rates of cellular respiration
Elevates basal metabolic rate
C.
Calcitonin
1. Made by the parafollicular cells
2. Inhibits dissolution of calcium from bone and
stimulates excretion of calcium in the kidneys to
lower blood calcium levels
D. Diseases of the Thyroid
1. Iodine deficiency leads to overstimulation of the
thyroid gland (no negative feedback on pituitary
gland) and growth of a goiter.
2. It also leads to hypothyroidism: low metabolic
rates, weight gain and lethargy, poor adaptation
to cold stress, and myxedema (accumulation of
fluids in subcutaneous connective tissues).
3. Grave’s Disease – hyperthyroidism
4. Cretinism results from hypothyroidism during
pregnancy to about 6 months after birth
Comparing Hyperthyroidism & Hypothyroidism
How iodine deficiency causes a goiter
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Sensor
Integrating center
Effector
Hypothalamus
–
TRH
Anterior
pituitary
Normal
thyroid
–
TSH
Thyroid
Low
T3 and T4
If iodine
inadequate
If iodine
adequate
T3 and T4
Low negative
feedback
Anterior
pituitary
Excess TSH
Thyroid
Hypertrophy–
produces goiter
Growth
(goiter)
Negative
feedback
Endemic goiter caused by low iodine
Symptoms of Hyperthyroidism
E. Parathyroid Glands
1. Generally 4 glands embedded in the back of the
thyroid gland
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Pharynx
Thyroid gland
Parathyroid
glands
Esophagus
Trachea
Parathyroid Glands, cont
2. Secrete parathyroid
hormone (PTH)
3. Hormone promotes a
rise in blood calcium
by acting on bones,
kidneys, and intestine
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Decreasing blood
Ca2+
–
Sensor
Integrating center
Effector
Parathyroids
Parathyroid
hormone
Kidneys
Reabsorption
of Ca2+
Bone
Dissolution of
CaPO4 crystals
Increased blood
Ca2+
Decreased urinary
excretion of Ca2+
Negative
feedback
VI. Pancreas and Other
Endocrine Glands
A.
Pancreas
1. The pancreas is both an endocrine and an
exocrine gland.
2. Endocrine cells are located in pancreatic islets
(islets of Langerhans).
a. Alpha cells: glucagon
b. Beta cells: insulin
Pancreas
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Pancreatic islet
(of Langerhans)
Gallbladder
Beta cell
Aorta
Alpha cell
Celiac
artery
Common bile duct
Tail of pancreas
Pancreatic duct
Duodenum
Body of pancreas
3.
Insulin
a. Primary hormone regulating plasma glucose
concentration.
b. Insulin is secreted by beta cells when blood
glucose levels rise after a sugary or carbohydrate
meal.
c. Its purpose is to lower blood glucose levels to the
“normal” range.
d.
Action of Insulin
1) Insulin binds to receptors on target cells.
a) Vesicles with GLUT4 carrier proteins bind to
membrane.
b) Glucose diffuses through GLUT4 channels by
facilitated diffusion
c) Occurs in adipose tissue, skeletal muscle, and
the liver.
2) Indirectly stimulates the enzyme glycogen
synthase in liver and skeletal muscles to promote
sugar storage
3) Stimulates adipose tissue to store fat
Action of Insulin
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1
Insulin
Insulin
receptor
GLUT4
Glucose
3
Translocation
4
P
Signaling
molecules
2
4
Translocation
Vesicles
3
4.
Glucagon
a. Antagonistic to insulin
b. Secreted by alpha cells when blood glucose
levels are low
c. Purpose is to raise blood glucose levels to a
“normal” range
d.
Action of Glucagon
1) Stimulates liver to hydrolyze glucagon into
glucose and release it into the blood
2) Stimulates gluconeogenesis, conversion of
noncarbohydrates into glucose
3) Stimulates lipolysis in adipose tissue so fat is
released and used as a fuel source instead of
glucose
Glucose Homeostasis
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Sensor
Integrating center
Blood
Glucose
in plasma
Effector
Blood
Pancreatic islets
α cells
Glucagon
β cells
Insulin
Glucose
in plasma
Pancreatic islets
α cells
Glucagon
β cells
Insulin
–
–
Glucose
in plasma
(a)
Glucose
in plasma
Cellular uptake
and utilization
of glucose
Cellular uptake
of glucose
Glycogenolysis
Gluconeogenesis
(b)
B.
Pineal Gland
1. Located on roof of third ventricle in the brain
2. Secretes the hormone melatonin
3. Regulated by the suprachiasmatic nucleus of the
hypothalamus through sympathetic neurons
a. Stimulates melatonin production when it gets
dark
b. Part of the regulation of circadian rhythms
c. Requires melanopsin found in the ganglion
cells of the retina
d. Secretion related to puberty, jet lag, and
seasonal affective disorder
Secretion of Melatonin
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CH3O
Melatonin
H H H O
C C N C CH3
H H
N
H
Pineal
gland
Day
Inhibition
Suprachiasmatic
nucleus (the
"biological clock")
Night
Stimulation
Retinohypothalamic
tract
Sympathetic
neurons
Superior cervical
ganglion
C.
Other Endocrine Glands
1. Gastrointestinal tract: Several hormones are
made in the stomach and small intestine to
regulate digestive processes; includes gastrin,
secretin, cholecystokinin
2. Gonads: Produce testosterone, estrogen, and
progesterone to regulate production of gametes
and secondary sexual characteristics
3. Placenta: produces human chorionic gonadotropin
(hCG) and samatomammotropin to regulate
pregnancy