The Endocrine System

How Hormones Elicit a Response

Binding of a hormone to its receptor
initiates a signal transduction pathway
leading to responses in the cytoskeleton,
enzyme activation, or a change in gene
expression
EXTRACELLULAR
CYTOPLASM
FLUID

Plasma membrane
1

Reception

Transduction

Response

Receptor
1

2
Relay molecules

Signaling
molecule

Activation
of cellular
response

External Signals induce two major types of

cellular responses
1. Changes in the activity or function of specific
enzymes and other proteins that pre-exist in
the cell.
FAST RESPONSE (G-Proteins)

2. Changes in the amounts of specific proteins

produced by a cell. (protein synthesis)
SLOW RESONSE

What types of receptors use

G-protein pathways?
Receptors for endocrine hormones
that control carbohydrate, amino
acid, and fat metabolism,
Glucagon receptor
ACTH (adrenocorticotropic
hormone)
Epinephrine receptor
Neurotransmitter receptors
- Epinephrine receptor
- Acetylcholine muscarinic

What is a G-protein?
Heterotrimeric proteins that bind GDP
and GTP
They are found on the inner surface of
the plasma membrane
They are associated with transmembrane
receptors (GPCRs)

All G protein-coupled receptors span

the membrane 7 times

What is a secondary
messenger?
Small, non-protein, water soluble molecules or
ions that are activated during a signal
transduction pathway and cause a cellular
event to happen
Examples: cAMP, cGMP, Ca2+, IP3(inositol
trisphosphate), DAG (diacylglyceral)
SECONDARY MESSENGERS ARE NOT
ENZYMES!

What is cyclic AMP (cAMP)?

(adenosine triphosphate)

G protein-coupled receptors (GPCRs) are

cell surface transmembrane receptors that
work with the help of a G protein
1. Substrate binds
to receptor,
activating it.
Receptor
changes shape
2. Activated
receptor binds
to G-protein,
activating that,
and GTP
replaces GDP

G protein-coupled
receptor

Plasma membrane

GDP

CYTOPLASM

G protein
(inactive)

Enzyme

1
Signaling
molecule

Activated
receptor

GTP
GDP
GDP

GTP

Inactive
enzyme

Figure 11.8bb

3. Activated G-protein
dissociates from
receptor, diffuses
across membrane,
and binds to enzyme.
Enzyme is activated
and elicits a cellular
response.

Activated
enzyme

GTP

Cellular
response

4. G-protein
hydrolysis GTP to GDP
and P, and is
inactivated and ready
for reuse.

GDP
Pi

Figure 11.12

First messenger
(signaling molecule
such as epinephrine)
G protein

Adenylyl
cyclase

GTP
G protein-coupled
receptor

ATP
cAMP

Secondary
messengers are
activated, turning on
Protein kinase A

Second
messenger
Protein
kinase A

Cellular responses

The binding of a single hormone causes

a 106 amplification of target protein
Reception
Binding of epinephrine to G protein-coupled
receptor
(1 molecule)

Transduction
Inactive
G protein
Active G protein (102 molecules)
Inactive
adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive
protein kinase A
Active protein kinase A (104)
Inactive
phosphorylase kinase

Response

Active phosphorylase kinase (105)

Glycogen
Glucose 1-phosphate
(108 molecules)

Inactive
glycogen phosphorylase
Active glycogen phosphorylase (106)

The IP3 secondary messenger releases

Ca2+ from cellular stores [(vasopressin,
thyroid stimulating hormone(TSH)]

Sometimes the
end result of
signal
transduction by a
hormone is gene
regulation

Growth factor

Reception

Receptor

Phosphorylation
cascade Transduction

CYTOPLASM

Inactive
transcription
factor

Active
transcription
factor

Response

DNA
Gene

NUCLEUS

mRNA

tokine Receptor: JAK/STAT

- Interferons
- Interleukins
- Erythropoietin

Receptor Tyrosine Kinases

- Insulin Receptor

The
Receptors for
Steroid
Hormones
are
intracellular

Signaling Between Cells

Triggers Specific Response
Pathways within the Target Cell
Types of signaling

1.
2.
3.
4.

Paracrine
Autocrine
Synaptic and Neuroendocrine
Endocrine

Local regulators
molecules that act over short distances,
reaching target cells solely by diffusion
1. paracrine
signaling - the
target cells lie
near the
secreting cells

RESPONSE
Paracrine signaling

2. autocrine
signaling - the
target cell is also the
secreting cell

Autocrine signaling

RESPONSE

 neurotransmitters - diffuse short distances and bind to

receptors on target cells
In neuroendocrine signaling, specialized neurosecretory
cells secrete molecules called neurohormones that travel to
target cells via the bloodstream
Synapse
Neuron

RESPONSE
(d) Synaptic signaling
Neurosecretory
cell
Blood
vessel
(e) Neuroendocrine signaling

RESPONSE

Endocrine System
Hormones - chemical signals secreted
into the circulatory system and
communicate regulatory messages within
the body
Hormones reach all parts of the body,
but only target cells have receptors for that
hormone
Blood
vessel
(a) Endocrine signaling

RESPONSE

Endocrine system consists of

ductless endocrine glands whose
hormones are delivered by the
circulatory system

Pineal gland
Hypothalamus
Pituitary gland

Other glands
- Heart
- Intestine
- liver

Thyroid gland
Parathyroid glands

Adrenal glands
Pancreas

Ovaries (female)

Testes (male)

Classification of Hormones
1.Peptides Short chains are peptides,
long chains are proteins (hydrophilic)
2. Amines - derived from the amino
acid tyrosine
includes catecholamines
(hydrophilic)
and thyroid hormone
(hydrophobic)
3. Steroids - derived from cholesterol

Water-soluble (hydrophilic) Lipid-soluble (hydrophobic)

Polypeptides

Steroids

0.8 nm
Insulin

Cortisol
Amines

catecholamine

Epinephrine

Thyroxine(T4) Thyroid hormon

The Nature of the Hormone

Determines the Following:
1.How it synthesized, stored and released
2.How it is transported in the blood
3.Cellular Mechanism of Action
4.Where its receptor is located

Water-soluble
hormones, such as
peptides and
catecholamines,
are secreted by
exocytosis, travel
freely in the
bloodstream, and
bind to cellsurface receptors

Lipid-soluble hormones
diffuse across cell
membranes, travel in the
bloodstream bound to
transport proteins, and
diffuse through the
membrane of target cells.
They bind to receptors in the
cytoplasm or nucleus of the
target cells
Example: Cortisol,
estrogen, testosterone

Multiple Effects of
Hormones
The same hormone may have
different effects on target cells that
have
Different receptors for the hormone
Different signal transduction pathways

For example, the hormone

epinephrine can increase blood flow
to major skeletal muscles, but
decrease blood flow to the digestive
tract

Hormones Exhibit Feedback

Mechanisms

Positive Feedback causes an

increase production of the
hormone
Negative Feedback causes
reduced production of the
hormone

Simple endocrine pathway

STIMULUS

Negative feedback

Endocrine
cell
Hormone

Target
cells
RESPONSE

Example: secretin signaling

Low pH in
duodenum
S cells of duodenum

Secretin ()

Pancreatic cells

Bicarbonate release

Simple neuroendocrine pathway

STIMULUS

Example: oxytocin signaling

Suckling

Sensory neuron

Positive feedback

Hypothalamus/
posterior pituitary
Neurosecretory
cell
Neurohormone

Target
cells
RESPONSE

Oxytocin ()

Smooth muscle in
mammary glands
Milk release

Hormones of the
Hypothalamus and the
Pituitary Gland

Hypothalamus
Pineal
and the
Pituitary glandgland

Cerebrum
Thalamus
Hypothalamus

Cerebellum

Pituitary
gland

Spinal cord

Many hormones are

regulated by the
hypothalamus and
secreted by the
posterior or anterior
pituitary gland

Hypothalamus
Posterior
pituitary

Anterior
pituitary

 The posterior pituitary stores and

secretes hormones that are made in
the hypothalamus
The anterior pituitary makes and
releases hormones under regulation
of the hypothalamus

The pituitary gland is

the size of a pea

Posterior Pituitary
Hormones
Protein Hormones
Synthesized in the hypothalamus and
transported to posterior pituitary gland
Antidiuretic hormone (ADH) or Vasopressin
regulates water retention in kidney, maintaining
plasma osmolarity (ie. increases water reabsorption
from kidney into blood)
Oxytocin regulates milk secretion by the mammary
glands

osterior Pituitary Gland

Hypothalamus

Neurosecretory
cells of the
hypothalamus
Axons

Neurohormone

Posterior
pituitary
Anterior
pituitary

HORMONE

ADH

Oxytocin

TARGET

Kidney tubules

Mammary glands,
uterine muscles

Anterior Pituitary Hormones

Protein hormones
Produced in the anterior pituitary
Release is controlled by hormones
secreted by the hypothalamus
- For example, the hypothalamus releases
-Growth-hormone releasing hormone
GHRH which stimulates the anterior
pituitary to secrete Growth hormone (GH),
which has metabolic effects

nterior Pituitary hormones

Hypothalamic
releasing and
inhibiting
hormones

Neurosecretory cells
of the hypothalamus

Portal vessels

HORMONE
Posterior
pituitary

Anterior pituitary
hormones

TARGET

FSH and LH

TSH

ACTH

Prolactin

MSH

GH

Testes or
ovaries

Thyroid

Adrenal
cortex

Mammary
glands

Melanocytes

Liver, bones,
other tissues

Tropic effects only

Nontropic effects only

Tropic and
nontropic effects

What is a Tropic Hormone?

An endocrine hormone that regulates the
Secretion of other endocrine hormones.
These are termed Topic Hormones

Example: Growth Hormone (GH)

secreted by the anterior pituitary
gland. Stimulates IGF-1 from liver cells

Growth Hormone (GH)

A tropic hormone secreted by the anterior

pituitary gland in response to GHRH
Hypothalamus

GHRH
Anterior Pituitary

GH
Metabolic Effects

Liver

Other hormones

Growth-promoting
action

Anterior Pituitary Hormones

Overproductio
n of GH during
childhood can
lead to
gigantism

Excessive GH production during

adulthood results in Acromegaly

FSH and LH

TSH

ACTH

Testes or
ovaries

Thyroid

Adrenal
cortex

Tropic effects only

Prolactin

MSH

GH

Mammary Melanocytes
glands

Liver, bones,
other tissues

Nontropic effects only

Tropic and
nontropic effects

TSH is another example

of a Tropic Hormone

2. Thyroid-stimulating hormone, TSH, is secreted by th

anterior pituitary gland.
TSH stimulate Thyroid hormone secretion by
the thyroid gland.

The Thyroid gland

consists of two lobes
Hormones produced:
1. Thyroid hormones
(T4 and T3)
2. Calcitonin
Thyroid
gland

Right lobe Trachea

Isthmus Left lobe

 Thyroid hormone refers to a pair of

hormones
Triiodothyronin (T3), with three
iodine atoms
Thyroxine (T4), with four iodine
atoms
Insufficient dietary iodine leads to
an enlarged thyroid gland, called a
goiter

Because they are hydrophobic, once

Thyroid Hormones diffuse into the
blood they are transported through
circulation bound to a protein.
Has a single binding
sight for T4

eps Leading to Thyroid Hormonal Effects

Hypothalamus

Thyrotropin-releasing hormone (TRH

Anterior pituitary

Thyroid-stimulating hormone (TSH

Thyroid

T3, T4
Target
cell

Where do you suppose the

cellular receptor for
thyroid hormone is
located?

Some Effects of Thyroid Hormone

1.Increases metabolic rate
2.Controls synthesis and
degradation of carbohydrate
fats and protein.
3. Increases heart rate
4. Development of reproductive
and nervous systems

egulation of Thyroid Hormone

1 Thyroid hormone
levels drop.

STIMULUS

End product of cascade,

thyroid hormone, creates
negative feedback.

Sensory
neuron
Hypothalamus
Neurosecretory
cell
TRH

2
The
hypothalamus secretes

TRH into
the blood. Portal
vessels carry TRH to anterior
pituitary.

3
TRH
causes anterior pituitary
to secrete TSH .

TSH

Anterior
pituitary

TSH
TSH circulation
throughout
body via blood
Thyroid
gland

Thyroid hormone
blocks
TRH release
6
and TSH release
preventing overproduction of
thyroid hormone.

Thyroid
hormone

4
TSH

stimulates
endocrine cells in
thyroid gland to
secrete T3 and T4 .

Circulation
throughout
body via blood
RESPONSE

5Thyroid

hormone
levels return to
normal range.

Facts:
1. Goiter is sometimes the end result of too
little thyroid hormone in the blood.
2. People with goiters at times show
elevated levels of TSH in the blood.
3. TSH also stimulates growth of the
thyroid
gland.
Problem: Explain the mechanistic causes
of this type of goiter.

Hypothyroidism
Failure of gland

deficiency of TRH, TSH

low iodine

Symptoms
reduced metabolic rate

weight gain
fatigue
slow reflexes

Hyperthyroidism
Overproduction of
TRH, TSH
Overproduction of
T4, T3

Symptoms
elevated metabolic rate

irritability
elevated heart rate
excessive mental alertness

Control of Blood Calcium

Two antagonistic hormones regulate
the homeostasis of calcium (Ca2+) in
the blood of mammals
Parathyroid hormone (PTH) is
released by the parathyroid glands
raises Ca2+ levels in blood
also stimulates vitamin D synthesis
Calcitonin is released by the thyroid
gland lowers blood Ca2+

Adrenal
medulla

Adrenal
The Adrenal Gland
cortex

Adrenal gland

Kidney

(a)

Fig. 7-19a

Catecholamines from the Adrenal

Medulla
epinephrine (adrenaline) and
norepinephrine (noradrenaline) hydrophilic
These hormones are members of a class of
compounds called catecholamines
They are secreted in response to stressactivated impulses from the nervous
system
They mediate various fight-or-flight
responses

pinephrine: short term stress hormon

Fight or Flight response

Trigger the release of glucose and fatty acids into

the blood
Increase oxygen delivery to body cells
Direct blood toward heart, brain, and skeletal
muscles and away from skin, digestive system, and
kidneys

(a)

Short-term stress response

and the adrenal medulla
Effects of epinephrine and norepinephrine:

Glycogen broken down to glucose;

increased blood glucose
Increased blood pressure
Increased breathing rate
Increased metabolic rate
Change in blood flow patterns, leading to
increased alertness and decreased digestive,
excretory, and reproductive system activity

In summary, the short

term stress response
increases amount of
energy needed for

Epinephrines Signal Transduction Pathw

EXTRACELLULAR FLUID
Hormone (epinephrine)
G protein

Adenylyl
cyclase

GTP
G protein-coupled
receptor

ATP
cAMP Second
messenger

Inhibition of
glycogen synthesis
Promotion of
glycogen breakdown

Protein
kinase A
CYTOPLASM

(a) Short-term stress response

(b) Long-term stress response

Hypothalamus

Stress

Nerve
impulses

Spinal
cord
(cross section)

Releasing
hormone
Neuron
Anterior pituitary
Blood vessel

Adrenal
medulla

Neuron

Adrenal
gland
Kidney
Secretion
of epinephrine and
norepinephrine

ACTH

Adrenal
cortex
Secretion of mineraloand glucocorticoids (cortisol)

Cortisol: The long-term stress hormo

- Glucocorticoid secreted from the Adrenal Cortex
-Released in response to stresses of
all types: physical, chemical,
physiological,
psychological or emotional.

Stress

Hypothalamus
Cortiotropin-releasing hormone
(CRH)

Anterior Pituitary
Adrenocorticotropic hormone
(ACTH)

Adrenal Cortex
Target
cell

Cortisol

Long-term stress response

and the adrenal cortex
(b)
Effects of
mineralocorticoids:

Effects of
glucocorticoids:

Retention of sodium
ions and water by
kidneys

Proteins and fats broken

down and converted to
glucose, leading to
increased blood glucose

Increased blood
volume and blood
pressure

Partial suppression of
immune system

Adrenal Cortex Steroid Hormones

Derived from cholesterol
Hydrophilic
Carried in blood bound to proteins
DHEA*

Cortisol

*
Produced
in male and female in small amounts

Sex Hormones of the

Gonads
The gonads, testes and ovaries, produce
most of the sex hormones: androgens,
estrogens, and progestins
All three sex hormones are found in both
males and females, but in significantly
different proportions
Synthesis of the sex hormones is controlled
by follicle-stimulating hormone (FSH)
and luteinizing hormone (LH) from the
anterior pituitary

Androgens: testosterone
Synthesized in the testis
stimulate development and maintenance
of the male reproductive system
Testosterone causes an increase in muscle
and bone mass.

Anabolic Steroids
Muscle-building steroids

hetically made steroids mimic the effect

tosterone
-Increases muscle mass
- causes hypertension and
cardiovascular disease

Estrogens: estradiol and progestero

Synthesized in the ovaries
responsible for maintenance of the
female reproductive system and the
development of female secondary
sex characteristics

All Steroid
Hormone
(estradiol)
Derived
Hormones,
including sex Estradiol
receptor
hormones, are
involved in
gene
NUCLEUS
regulation

EXTRACELLULAR
FLUID

Plasma
membrane
Hormone-receptor
complex
CYTOPLASM
DNA

mRNA
for vitellogenin

Vitellogenin

Bipotential gonad
Male duct
(Wolffian)

Regulation on
reproductive
structures in
human
development

Female duct
(Mllerian)

Embryo (XY or XX)

Absence of male
hormones

Testosterone
AMH

Ovary

Testis
Uterus
Vas
deferens
Seminal
vesicle

Oviduct
Bladder

Male (XY) fetus

Bladder

Female (XX) fetus

Regulation of Energy
Storage
Glycogen storage polymer of
carbohydrates found in liver and
muscle cells
Excess energy is stored in fat in
adipose cells
When fewer calories are taken in
than expended, the human body
uses liver glycogen first, then
muscle glycogen and fat

The hormones insulin and glucagon

regulate glucose metabolism
The liver is the site for glucose
homeostasis
A carbohydrate-rich meal raises insulin
levels, which triggers the synthesis of
glycogen
Low blood sugar causes glucagon to
stimulate the breakdown of glycogen
Insulin
lowers
blood glucose
and release
glucose

*
* Glucagon raises blood glucose

egulation of Glucose homeostasi

The Pancreatic Hormones: insulin and glucagon

lpha cells- secrete glucagon

eta cells secrete insulin
Islet of Langerhans

se is transported across the cell membra

Glucose transporters (facilitated diffusion

ulin stimulates recruitment of glucose transporters to

membrane, which will facilitate import of glucose

The brain and liver

do not respond to
insulin. Their
receptors are not
dependent upon
insulin.

Diabetes Mellitus
Type I: - Insulin dependent
- Autoimmune disorder
- Lack of insulin secretion due to
defective
pancreatic beta cells
- Prevalent in children
Type II: - Non-insulin dependent
- Due to target cells insulin resistance
(defect in
insulin receptor or failure to recruit
glucose
transporter proteins to the cell