Chapter 18 - Dr. Gerry Cronin

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Chapter 18
The Endocrine
System
Introduction
• The nervous and endocrine systems
coordinate all of the body systems
 The nervous system does so through the action
of neurons, and the neurotransmitters they
secrete
 The endocrine
system uses
hormones produced
by endocrine structures
to produce their
effects
Types of Hormones
• Hormones are simply mediator molecules
that have effects on cells in the local
environment, or in a distant part of the body
 Some hormones, called autocrine hormones are
local hormones that are secreted, and bind to the
same cell. We will see examples of
autocrine stimulation
when we study the
immune system in
chapter 22
Types of Hormones
• Hormones as mediator molecules …
 Paracrine hormones are local hormones that are
secreted into interstitial fluid and act on nearby
cells
Types of Hormones
• Hormones as mediator molecules …
 Endocrine hormones are secreted into interstitial
fluid and then absorbed into the bloodstream to
be carried systemically
to any cell that
displays the
appropriate type
of receptor
Solubility of Hormones
Hormones can be divided into two broad
chemical classes. This chemical classification
is useful because the two classes exert their
effects differently
– Lipid soluble hormones bind to receptors in the
cytoplasm or nucleus of the cell
– Water soluble hormones bind to receptors on
the surface of the cell
Solubility of Hormones
Lipid soluble hormones consist of steroid
hormones, thyroid hormones, and the gas
nitric oxide
– Steroid hormones are derived from cholesterol
– Thyroid hormones (T3 and T4) are synthesized by
attaching iodine to the amino acid tyrosine
– The gas nitric oxide (NO) is both a hormone and a
neurotransmitter. Its synthesis is catalyzed by the
enzyme nitric oxide synthase
Solubility of Hormones
• Lipid soluble hormones require a carrier
protein for transport in the watery
environment of the blood
 Once they arrive at their
destination, however, they
are able to freely pass
through the plasma
membrane to bind to
receptors located in the cytoplasm
or the nucleus of the target cell
Lipid-Soluble
Hormone
Action
Free hormone
Blood capillary
1 Lipid-soluble
Transport
protein
hormone
diffuses into cell
2 Activated
Nucleus
Receptor
receptor-hormone
complex alters
gene expression
DNA
Cytosol
mRNA
3 Newly formed
mRNA directs
synthesis of
specific proteins
on ribosomes
Ribosome
New
protein
4 New proteins alter
cell's activity
Target cell
Solubility of Hormones
Water soluble hormones include peptide and
protein hormones (and others with an amine
group), and a group of local hormones derived
from the arachidonic acid on our cell
membranes called eicosanoids
– Peptide hormones and protein hormones are
amino acid polymers
– The two major types of eicosanoids are
prostaglandins and leukotrienes – both play a role
in mediating the inflammatory response
Solubility of Hormones
• Water soluble hormones are easy to
transport in the watery blood. The plasma
membrane of target cells, however, is
impermeable to them
 Water soluble hormones exert their effects by
binding to receptors exposed to the interstitial
fluid on the surface of target cells
• the hormone binding to its receptor acts as the first
messenger in a cascade of signal transduction
Solubility of Hormones
The first messenger (the hormone) then causes
production of a second messenger inside the cell,
where specific hormone-stimulated responses
take place
– One common second messenger is
cyclic AMP (cAMP). Neurotransmitters, neuropeptides, and
several sensory transduction
mechanisms (vision) also act via
second-messenger systems
Water-Soluble
Hormone
Action
Blood capillary
1 Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Water-soluble
hormone
Adenylate cyclase
Receptor
Second messenger
G protein
ATP
cAMP
2 Activated adenylate
cyclase converts
ATP to cAMP
Protein kinases
6 Phosphodiesterase
inactivates cAMP
3 cAMP serves as a
second messenger
to activate protein
kinases
Activated
protein
kinases
4 Activated protein
Protein
kinases
phosphorylate
cellular proteins
ATP
ADP
Protein— P
5 Millions of phosphorylated
proteins cause reactions that
produce physiological responses
Target cell
Effects of Hormones
• Prostaglandins (PGs) and leukotrienes are
eicosanoid hormones with local control. They
are synthesized from membrane lipids and
have widespread effects
 PG’s mediate pain, platelet aggregation, fever, and
inflammation. They regulate smooth muscle
contraction, gastric acid secretion, and airway size
• aspirin is a drug that works by inhibiting an enzyme
necessary for synthesis of certain PGs: the ones that
facilitate pain and the inflammatory response
Effects of Hormones
 Endocrine hormones control a variety of
physiological processes. Among other things, they:
– Balance the composition and volume of body fluids
– Regulate metabolism and energy production
– Direct the rate and timing of growth and development
– Exert emergency control during physical and mental
stress (trauma, starvation, hemorrhage)
– Oversee reproductive mechanisms
EFFECTS OF HORMONES
(Interactions Animation)
o
Introduction to endocrine hormones: Regulation,
secretion and concentration
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Endocrine System Glands
Glands that secrete endocrine hormones into
the bloodstream are called endocrine glands
– They are one of two major types of glands in the
body, the other being exocrine glands (which
secrete their products into ducts )
In this chapter we will focus our
study on the endocrine glands
and the widespread effects of
endocrine hormones
Control of Hormones
When stimulated, an endocrine gland will
release its hormone in frequent bursts,
increasing the concentration of the hormone
in the blood
– Hormone secretion is regulated by signals from
the nervous system, chemical changes in the
blood, and other hormones
• Most hormonal regulatory systems work via negative
feedback, but a few operate via positive feedback
Control of Hormones
• In a negative feedback system the hormone
output reverses a particular stimulus. For
example:
 Blood Ca2+ level is controlled by the parathyroid
hormone (PTH). If blood Ca2+ is low, there is a
stimulus for the parathyroid glands to release
more PTH. PTH then exerts its effects in the body
until the Ca2+ level returns to normal. If the level
gets too high the body will cease PTH production
and secrete calcitonin lower the Ca2+ levels.
Control of Hormones
• This example shows how PTH and calcitonin have
negative feedback influence on one another
Control of Hormones
In a positive feedback
system the hormone
output reinforces and
encourages the stimulus.
For example, during
childbirth, the hormone
oxytocin stimulates
contractions of the uterus,
and uterine contractions in
turn stimulate more
oxytocin release, a positive
feedback effect
CONTROL OF HORMONES
(Interactions Animation)
o
Hormones Summary
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The Endocrine System
The endocrine system consists of the
pituitary, thyroid, parathyroid, adrenal and
pineal glands
– Some of the most important glands of the
endocrine system are not exclusively endocrine
glands: The hypothalamus, thymus, pancreas,
ovaries, and testes are paramount;
the kidneys, stomach, liver,
small intestine, skin, heart,
and placenta also contribute
The Endocrine System
The Hypothalamus
The hypothalamus is the major link between
the nervous and endocrine systems
– It receives input from several regions in the brain
including the
thalamus, the
RAS, and
the limbic
system
The Pituitary Gland
The hypothalamus mainly controls the
pituitary gland, which is also called the
hypophysis
– The pituitary hangs down from the
hypothalamus
on a stalk called the infundibulum
– The gland is divided into an anterior
adenohypophysis and a posterior
neurohypophysis - the anterior pituitary
accounts
for about 75% of the total
weight of the gland
The Adenohypophysis
The anterior pituitary (adenohypophysis) is
anatomically and functionally connected to
the hypothalamus by blood vessels that form
a portal system called the hypophyseal portal
system
– In a portal system, blood flows from one capillary
network into a portal vein, and then into a
second capillary network before returning to the
heart
• The name of the portal system indicates the location
of the second capillary network
The Adenohypophysis
Specialized neurosecretory cells in the
hypothalamus secrete releasing hormones
into the hypophyseal portal system
that supplies blood to the
anterior pituitary
gland
The Adenohypophysis
• The second capillary system of the
hypophyseal portal system delivers the
hypothalamic releasing hormones to the
anterior pituitary
 5 types of anterior pituitary cells secrete seven
hormones
Anterior Pituitary Hormones
Hypothalamus
Hormone
Growth hormone
releasing hormone
(GHRH)
Thyrotropin
releasing hormone
(TRH)
Prolactin releasing
hormone
(PRH)
Hormone released
from
Adenohypophysis
Major Function/ Target
Human Growth
Hormone (hGH)
Also called somatostatin,
stimulates secretion of
insulin-like growth factors
(IGFs) that promote growth
Thyroid Stimulating
Hormone (TSH)
Stimulates synthesis and
secretion of thyroid
hormones by the thyroid
gland
Prolactin (PRL)
Stimulates breast growth,
and development of the
mammary glands
Anterior Pituitary Hormones
Hypothalamus
Hormone
Hormone released
from
Adenohypophysis
Major Function/ Target
Gonadotropic
releasing hormone
(GnRH)
Follicle Stimulating
hormone (FSH)
Ovaries initiate development
of oocytes; testes initiate
development of spermatozoa
Gonadotropic
releasing hormone
(GnRH)
Luteinizing hormone
(LH)
Ovaries stimulate ovulation;
testes stimulate testosterone
production
Anterior Pituitary Hormones
Hypothalamus
Hormone
Corticotropin
releasing hormone
(CRH)
Corticotropin
releasing hormone
(CRH)
Hormone released
from
Adenohypophysis
Major Function/ Target
Adrenocorticotropic
Hormone (ACTH)
Stimulates release of
mineralocorticoid,
glucocorticoid, and androgen
hormones from the adrenal
cortex
Melanocyte
Stimulating hormone
(MSH)
Stimulate the production and
release of melanin by
melanocytes in skin and hair.
MSH signals to the brain have
effects on appetite and sexual
arousal
ANTERIOR PITUITARY HORMONES
(Interactions Animation)

hGH Growth and
Development
• hGH Stimulating
Glycogenolysis
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ANTERIOR PITUITARY HORMONES
(Interactions Animation)

ACTH and Cortisol
• Cortisol
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ANTERIOR PITUITARY HORMONES
(Interactions Animation)
• TRH and TSH
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Anterior Pituitary Hormones
• Tropic hormones are hormones produced
and secreted by the anterior pituitary that
target other endocrine glands
 All hormones in the previous lists target other
endocrine glands (are trophic hormones) except
hGH, Prolactin, and MSH, which directly target
the end organs
The neurohypophysis
• The posterior pituitary (neurohypophysis) is
embryologically derived from and anatomically
connected to the hypothalamus – it releases, but
does not synthesize any hormones
 When stimulated, neurosecretory
cells in the hypothalamus
release oxytocin and
ADH from their axon
terminals located in
the posterior pituitary
The neurohypophysis
• Oxytocin targets smooth muscle in the uterus
and breasts. In the uterus, oxytocin
stimulates uterine contractions, and in
response to the sucking from an infant,
oxytocin stimulates “milk letdown” in the
breasts
• ADH targets the collecting ducts in the kidney
and sweat glands in the skin to minimize
water loss. It also directly causes arterioles to
constrict thereby increasing blood pressure
The neurohypophysis
• This graphic
demonstrates the
regulation of ADH
secretion
POSTERIOR PITUITARY HORMONES
• Antidiuretic Hormone Animation
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Pituitary Gland Disorders
• Acromegaly occurs as a result of excess HGH
during adulthood. This disease is marked by
enlargement and elongation of the bones of
the face, jaw, cheeks, and hands (the long
bones of
the extremities are
unaffected because the
growth plates have
already closed)
Pituitary Gland Disorders
• Diabetes Insipidus (DI) is very different from
the disease called sugar diabetes (diabetes
mellitus)
 DI is caused by the insufficient release of ADH
from the neurohypophysis. Without ADH acting
on the collecting ducts in the kidneys, the
normal urine output of 1–1.5 liters per day
increases to over 2.5 liters per day and
dehydration and hypernatremia results
The Thyroid Gland
• The butterfly-shaped thyroid gland is located
inferior to the larynx and anterior to the
trachea. It has two laterally placed lobes
separated by a bridge-like isthmus
The Thyroid Gland
• Most of the thyroid gland is composed of
spherical groups of follicular cells called
thyroid follicles
 The follicles store
a 100-day supply
of its two hormones
in an inactive
gel-like substance
called TGB (for
thyroglobulin)
Thyroid Hormones
• TGB is a large glycoprotein made
from the oxidation and
iodination of molecules of the
amino acid. tyrosine
• The two hormones released
from TGB are:
thyroxine or T4
(tetraiodothyronine)
and T3
(triiodothyronine)
Thyroid Hormones

In the blood, T3 and T4 are bound to pre-albumins, albumin,
and a specific carrier protein called thyroid-binding globulin
(TBG)
 Most T4 released from the thyroid is converted
“peripherally” (by enzymes in the blood) into T3 ,
which is a more active hormone
• Together with hGH and insulin, thyroid
hormones accelerate body growth,
particularly the growth of the nervous and
skeletal systems
Thyroid Hormones
• Thyroid-stimulating hormone (TSH) is released
by the anterior pituitary gland in response to
TRH secreted into the portal system
 The hypothalamus
responds to higher
circulating levels of
T3 and T4 via negative
feedback to inhibit
TRH secretion
1 Low blood levels of T3
Thyroid Hormone
Regulation
and T3 or low metabolic
rate stimulate release of
Hypothalamus
TRH
2 TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs
5 Elevated
T3inhibits
release of
TRH and
TSH
(negative
feedback)
TSH
3 TSH released into
blood stimulates
thyroid follicular cells
Anterior
pituitary
4 T3 and T4
Thyroid
follicle
released into
blood by
follicular cells
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones
Thyroid Hormones
• A goiter is an enlargement of the thyroid
gland and may be associated with
hyperthyroidism, hypothyroidism, or
euthyroidism
 In many third-word countries
dietary iodine intake is inadequate;
the resultant low level of thyroid
hormone in the blood stimulates
secretion of TSH, which causes
thyroid gland enlargement
The Parathyroid Glands
• The parathyroid glands are small, round
masses of tissue attached to the posterior
surface of the lateral lobes of the thyroid
gland
 There are usually two
parathyroid glands
attached to each
lobe of the thyroid,
one superior and one inferior
Parathyroid Hormones
• Calcitonin (Thyrocalcitonin) is made by the
parafollicular (C-cells) of the thyroid gland
and
when secreted lowers the blood calcium level
• An increase in blood calcium will stimulate
the C-cells of the thyroid to secrete calcitonin
 Increased calcitonin will cause a negative
feedback inhibition of parathyroid hormone
(PTH) which
causes a decrease in blood calcium and an increase in
blood phosphate levels
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