Endocrine system

Dr. Victor J. Samillan

ES and Homeostasis
Homeostasis


Tissues can be targeted by multiple hormones

Hormones can act synergistically, permissively, or antagonistically
Synergistic effects of
hormones on blood
glucose concentration
Peptide Hormones
Synthesis/transport/half-life
Storage?
Multiple processing patterns for protein hormones
Hormone-Receptor
interactions
Definition: a protein that binds a ligand with high
affinity and low capacity. This binding must be
saturuable.
A tissue becomes a target for a hormone by
expressing a specific receptor for it. Hormones
circulate in the blood stream but only cells with
receptors for it are targets for its action.

Agonist vs. Antagonist
Agonists are molecules that bind the receptor
and induce all the post-receptor events that lead
to a biologic effect. In other words, they act like
the "normal" hormone, although perhaps more
or less potently
Antagonists are molecules that bind the
receptor and block binding of the agonist, but
fail to trigger intracellular signaling events

Metabolic clearance rate
(MCR)

Defines the quantitative removal of hormone from
plasma
The bulk of hormone is cleared by liver and kidneys
Only a small fraction is removed by target tissue
protein and amine hormones bind to receptors and are
internalized and degraded
Steroid and thyroid hormones are degraded after
hormone-receptor complex binds to nuclear chromatin
99% of excreted hormone is degraded or
conjugated by Phase I and Phase II enzyme systems
MCR of some hormones
Hormone

Half-life

Amines

2-3 min

Thyroid hormones: T4
T3

6.7 days
0.75 days

Polypeptides

4-40 min

Proteins

15-170 min

Steroids

4-120 min

Methods of intercellular
communication by
secreted molecules
(a) Endocrine signaling
Blood
vessel
Response
Response
Response
Synapse
Response
Response
(b) Paracrine signaling short distances
(c) Autocrine signaling short distances
Neuron
(d) Synaptic signaling
Neurosecretory
cell
Blood
vessel
(e) Neuroendocrine signaling
Different receptors Same receptors but different
intracellular proteins (not shown)
Different cellular
responses
Different cellular
responses
Epinephrine Epinephrine Epinephrine
receptor receptor receptor
Glycogen
deposits
Vessel
dilates.
Vessel
constricts.
Glycogen
breaks down
and glucose
is released
from cell.
(a) Liver cell (b) Skeletal muscle
blood vessel
Intestinal blood
vessel
(c)
Figure 45.9
Types of receptors
Second messengers for cell-
surface receptors
Second messenger systems include:
Adenylate cyclase which catalyzes the conversion of
ATP to cyclic AMP;
Guanylate cyclase which catalyzes the conversion of
GMP to cyclic GMP (cyclic AMP and cyclic GMP are
known collectively as cyclic nucleotides);
Calcium and calmodulin; phospholipase C which
catalyzes phosphoinositide turnover producing inositol
phosphates and diacyl glycerol.

Hormones and their receptors
Hormone

Class of
hormone

Location

Amine
(epinephrine)

Water-soluble

Cell surface

Amine (thyroid
hormone)

Lipid soluble

Intracellular

Peptide/protein

Water soluble

Cell surface

Steroids and
Vitamin D

Lipid Soluble

Intracellular

Binding vs. biological response
Spare receptors Amplification by
2
nd
messenger
Spare Receptors
Maximum response with 2-3% receptor
occupancy
97% of receptors are spare
Maximum biological response is achieved when
all of the receptors are occupied on an average
of <3% of the time
The greater the proportion of spare receptors,
the more sensitive the target cell to the
hormone
Lower concentration of hormone required to
achieve half-maximal response
Spare receptors
In most systems the maximum biological
response is achieved at concentrations of
hormone lower than required to occupy all of
the receptors on the cell.
Examples:
insulin stimulates maximum glucose oxidation in
adipocytes with only 2-3% of receptors bound
LH stimulates maximum testosterone production in
Leydig cells when only 1% of receptors are bound
Control Pathways and Feedback Loops
There are
three types of
hormonal
control pathays

Pathway Example
Stimulus
Low blood
glucose
Receptor
protein
Pancreas
secretes
glucagon ( )
Endocrine
cell
Blood
vessel
Liver
Target
effectors
Response
Pathway Example
Stimulus Suckling
Sensory
neuron
Hypothalamus/
posterior pituitary
Neurosecretory
cell
Blood
vessel
Posterior pituitary
secretes oxytocin
( )
Target
effectors
Smooth muscle
in breast
Response Milk release
Pathway Example
Stimulus
Hypothalamic
neurohormone
released in
response to
neural and
hormonal
signals
Sensory
neuron
Hypothalamus
secretes prolactin-
releasing
hormone ( )
Neurosecretory
cell
Blood
vessel
Anterior
pituitary
secretes
prolactin ( )
Endocrine
cell
Blood
vessel
Target
effectors
Response
Mammary glands
Milk production
(c) Simple neuroendocrine pathway
(b) Simple neurohormone pathway
(a) Simple endocrine pathway
Hypothalamus
Glycogen
breakdown,
glucose release
into blood
Figure 45.2ac
Figure 45.8-2
EXTRACELLULAR
FLUID
Hormone
(estradiol)
Estradiol
(estrogen)
receptor
Plasma
membrane
Hormone-receptor
complex
NUCLEUS
DNA
CYTOPLASM
Vitellogenin
mRNA
for vitellogenin
Figure 45.7-2
Epinephrine
G protein
Adenylyl
cyclase
G protein-coupled
receptor
GTP
ATP
cAMP
Second
messenger
Inhibition of
glycogen synthesis
Promotion of
glycogen breakdown
Protein
kinase A
Figure 45.6-2
Lipid-
soluble
hormone
SECRETORY
CELL
Water-
soluble
hormone
VIA
BLOOD
Signal receptor
TARGET
CELL
OR
Cytoplasmic
response
Gene
regulation
(a) (b)
Cytoplasmic
response
Gene
regulation
Signal
receptor
Transport
protein
NUCLEUS
Lipid-soluble (hydrophobic) Water-soluble (hydrophilic)
Polypeptides Steroids
0.8 nm
Insulin Cortisol
Amines
Epinephrine Thyroxine
3 Chemical
classes of
hormones
Because peptides are
impermeable, they must use
membrane receptors and
second messenger signal
transduction mechanisms to
produce the desired effects.

Most use g-protein coupled
receptors, but some use
tyrosine kinase type
receptors (i.e. insulin)
STIMULUS
Hypothalamus
Releasing Hormone
(Release-Inhibiting Hormone)

Pituitary
Stimulating Hormone

Gland
Hormone
Target
Characteristics of hypothalamic
releasing hormones
Secretion in pulses
Act on specific membrane receptors
Transduce signals via second messengers
Stimulate release of stored pituitary hormones
Stimulate synthesis of pituitary hormones
Stimulates hyperplasia and hypertophy of target
cells
Regulates its own receptor
Hypothalamic releasing hormones
Hypothalamic releasing hormone

Effect on pituitary

Corticotropin releasing hormone
(CRH)

Stimulates ACTH secretion

Thyrotropin releasing hormone
(TRH)

Stimulates TSH and Prolactin
secretion

Growth hormone releasing
hormone (GHRH)

Stimulates GH secretion

Somatostatin

Inhibits GH (and other hormone)
secretion

Gonadotropin releasing hormone
(GnRH) a.k.a LHRH

Stimulates LH and FSH
secretion

Prolactin releasing hormone (PRH)

Stimulates PRL secretion

Prolactin inhibiting hormone
(dopamine)

Inhibits PRL secretion

Hypothalamus and Pituitary
The hypothalamus-pituitary unit is the most dominant portion
of the entire endocrine system.
The output of the hypothalamus-pituitary unit regulates the
function of the thyroid, adrenal and reproductive glands and
also controls somatic growth, lactation, milk secretion and
water metabolism.

Three major groups
1. Posterior
pituitary/hypothalamus
Vasopressin (ADH)
Oxytocin
2. Anterior
pituitary/hypothalamus
3. Catecholamines of the
adrenal medulla
Tropic effects only:
FSH
LH
TSH
ACTH
Nontropic effects only:
Prolactin
MSH
Nontropic and tropic effects:
GH
Hypothalamic
releasing and
inhibiting
hormones
Posterior
pituitary
Neurosecretory
cells of the
hypothalamus
Portal vessels
Endocrine cells
of the anterior
pituitary
Pituitary
hormones
HORMONE FSH and LH TSH ACTH Prolactin MSH GH
TARGET Thyroid Melanocytes
Testes or
ovaries
Adrenal
cortex
Mammary
glands
Liver, bones,
other tissues
Figure 45.16
Pineal
gland
Cerebellum
Spinal cord
Cerebrum
Thalamus
Hypothalamus
Pituitary
gland
Posterior
pituitary
Anterior
pituitary
Hypothalamus
Figure 45.14
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
2. Anterior pituitary
hypothalamus
Prolactin
Thyroid stimulating
hormone (TSH)
Adrenocorticotropic
hormone (ACTH)
Growth hormone (GH)
Follicle stimulating hormone
(FSH)
Leutinizing hormone (LH)



Most target other
endocrine glands or cells
Example of Hormone Regulation Vasopressin (ADH)
Regulation of body water is a response to ECF volume changes (in particular, blood
volume)
When blood volume changes, volume receptors in the blood vessels and atria
respond
Carotid sinus and aortic baroreceptors
Afferent nerves from these receptors go to the cardiovascular center in the
brainstem
Increased pressure would signal the center to
Decreased pressure would signal the center to
When blood volume changes, stretch receptors in the atria also respond
Increased pressure also signals the cardiovascular center to
Increased pressure signals the hypothalamus (this is where ADH release is
controlled)


When blood volume
increases, filtration in the
kidney is adjusted so that
more fluid is filtered per
minute
Typically, under normal
situations, the kidneys are
not under the influence of
ADH and water follows ions
as they pass through the
kidney tubules
There are few aquaporin
molecules in the cell
membranes of the kidney
collecting ducts in the
absence of ADH. They are
stored inside the cells.

Influence of ADH on the Collecting Ducts
Feedback Loop for ADH
Negative feedback
What regulates NaCl?
Regulation of Na+
Increasing osmolarity of the blood stimulates thirst behaviors, and increases
ADH secretion. Drinking and preventing water loss from the kidneys,
decreases blood osmolarity
How would this graph
change if an individual
had hypertension (high
blood pressure)?
Long-term regulation of Na+
Under the control of aldosterone; it increases Na+ reabsorption into the
blood from the kidney filtrate
What will happen to plasma [K+]?
What will be the overall effect on plasma osmolarity?

Oxytocin
Stimulates uterine contractions during childbirth by
mobilizing Ca
2+
through a PIP
2
-Ca
2+
second-messenger
system
Also triggers milk ejection (letdown reflex) in women
producing milk
Plays a role in sexual arousal and orgasm in males and
females