Topic 1 Endocrine System
Topic 1 Endocrine System
Topic 1 Endocrine System
ENDOCRINE
SYSTEM
Section 1 Introduction
I. Organization of Endocrine System
The functions of the body are regulated by
• the nervous and
• the endocrine system.
.
Endocrine glands:
•Glands that do not use ducts to convey the
secretion (hormornes) to a neighboring target
(ductless glands as opposed to exocrine gld.).
•Hormones circulate all over the body in the
blood but may produce effects only in selected
sites.
•The target organ(s) may or may not be near
the site of production of the hormone.
A hormone –
--chemical substance
--is secreted into the internal body fluids by
one specialized cell or a group of cells and
--has a physiological control effect on other
cells of the body.
II. Endocrine vs. Nervous Syste
Major communication systems in the body
Integrate stimuli and responses to changes
in external and internal environment
Both are crucial to coordinated functions of
highly differentiated cells, tissues and
organs
Unlike the nervous system, the endocrine
system is anatomically discontinuous.
Nervous system
Prostaglandins
Gut hormones
cc
Autocrines
Secreted by cell, gets into interstitial fluid and
acts on receptors on same cells
Cytokines: act as
hormones
Paracrines
Autocines
IV. Classification of Hormones
1. Proteins and Polypeptides, including hormones
secreted by the anterior and posterior pituitary
gland, the pancreas (insulin and glucagon), the
parathyroid gland (parathyroid hormone), and many
others.
2. Steroids secreted by the adrenal cortex (cortisol
and aldosterone), the ovaries (estrogen and
progesterone), the testes (testosterone), and the
placenta (estrogen and progesterone)
E
R L
SO RO
UR TE
EC ES
PR OL
CH
3. Derivatives of the amino acid tyrosine,
secreted by the thyroid (thyroxine and
triiodothyronine) and the adrenal medullae
(epinephrine and norepinephrine)
V. Properties of the hormone effect
1. Specificity
The special feature of the the target cells is the
presence of receptors which can “attract” and
interact with the hormone.
The receptors may be present either on the
plasma membrane, or in the cytoplasm, or in the
nucleus.
These receptor molecules are protein in nature
and may contain carbohydrate or phospholipid
moieties.
2. Signal Transmission
The role of the hormones is to transit the
regulatory signals from the control (endocrine)
system to the target cells (organs or glands).
It could enhance or inhibit some function of the
target.
3. High Biological Efficiency
Low plasma concentration (nmol – pmol/L)
great regulatory function
Signal
amplification
during the
transmembrane
and
intracellular
transmission
4. Interaction Between the Hormones
(i) Synergistic effects. When two or more
hormones work together to produce particular
result their effect are said to be synergistic.
These effects may be additive or complementary.
Additive: Same effect of the hormones on one
target organ, for example, epinephrine and
norepinephrine on the heart rate
Complementary: Work on different stages of a
physiological procedure, for example, FSH
(initiation) and testosterone (maintenance) on
spermatogenesis
(ii) Permissive effect. A hormone is said to have a
permissive effect on the action of a second
hormone when it enhances the responsiveness of a
target organ to the second hormone or when it
increases the activity of the second hormone.
Estrogen – Expression of progesterone receptors on
uterus – progesterone effect on the uterus.
Glucocorticoids – effects of catecholamines on
cardiovascular system
(3) Antagonist Effects. In some situations the
actions of one hormone antagonize the effects of
another.
Lactation during pregnancy is prevented because the
high concentration of estrogen in the blood inhibits
the milk secretion and action of prolactin.
VI. Mechanisms of Hormonal Action
The first step of a hormone’s action is to bind to
specific receptors at the target cell.
Locations for the different types of hormones:
1) On the surface of the cell membrane.
protein, peptide, and catecholamine hormones
2) In the cell cytoplasm.
steroid hormones
3) In the cell nucleus.
1.Second Messenger Mechanisms for
Mediating Intracellular Hormonal Functions
(1) Steroid
hormones
increase protein
synthesis
(2) Thyroid
hormones
increase gene
transcription in
the cell nucleus
Section 2 The Pituitary Hormones and Their
Control by the Hypothalamus
I. Anatomical and
Functional
Connection
Between the
Hypothalamus
and Pituitary
(hypothalamo-
hypophyseal
portal system and
tract)
Location of the Pituitary
1. The Pituitary Gland
Anterior
pituitary,
also known
as the
adenohypop
hysis,
Important peptide hormones that secreted by
the anterior pituitary and the targets:
TSH, Thyroid
stimulating hormone
ACTH,
Adrenocorticotropin
hormone
FSH, Follicle-
stimulating hormone
LH, Luteinizing
hormone
MSH, Melanophore-
stimulating hormone
GH, Growth
Hormone;
PRL, Prolactin
The posterior pituitary, also known as the
neurohypophysis.
Two important peptide hormones that secreted
by the posterior pituitary,
ADH
(or vasopressin)
oxytocin
2. Relationship Between the Hypothalamus and
Anterior Pituitary
Neurons in
the
hypothalamus
secreted
releasing
hormones
into the blood
vessels of the
hypothalamo-
hypophyseal
portal system.
These releasing hormones regulate the anterior
pituitary to secrete its hormones in the general
circulation.
3. Hormones Secreted by the Hypothalamus and
Their Effects on Anterior Pituitary
Corticotropin-releasing hormone (CRH) – Stimulates
secretion of ACTH (adrenocorticotropic hormone)
Gonadotropin-releasing hormone (GnRH) Stimulates
secretion of FSH (follicle-stimulating hormone) and LH
(luteinizing hormone)
Thyrotropin-releasing hormone (TRH)-stimulates
secretion of TSH (thyroid-stimulation hormone)
Melanocyte-stimulating hormone release inhibiting
factor (MIF)-inhibits secretion of MSH ( Melanocyte-
stimulating hormone)
Melanocyte-stimulating hormone releasing factor
(MRF)-stimulate secretion of MSH
Growth hormone release inhibiting hormone (GHRIH)
or Somatostatin (SS) – inhibits secretion of growth
hormone
Growth hormone-releasing hormone (GHRH)–
stimulates growth hormone secretion
Prolactin-inhibiting factor (PIF)- inhibits prolactin
secretion
Prolactin-releasing factor (PRF)-stimulates prolactin
section
4. Hormones Secreted
from the Posterior
Pituitary
vasopressin and
oxytocin
produced in neuron
cell bodies within the
supraoptic and
paraventricular nuclei
of the hypothalamus
transported to the posterior pituitary by nerve fibers of
the hypothalamo-hypophyseal tract.
II. Physiological Function of Hormones Secreted
From Anterior and Posterior Pituitary
1.Growth Hormone
(1) Physiological functions of growth hormone.
i) Growth effect
Growth hormone stimulates cell division, especially in
muscle and epiphyseal cartilage of long bones.
The result is muscular growth as well as linear growth.
GH also stimulates growth in several other tissues,
e.g.
skeletal muscle, heart, skin, connective tissue,
liver, kidney, pancreas, intestines, adrenals and
parathyroids.
Hypersecretion of GH leads to cause gigantism in
children and acromegaly in adult.
Hyposection of GH results in dwarfism during
childhood.
Effect of
hypophysectomy
on growth of the
immature rhesus
monkey.
Both monkeys
were the same
size and weight 2
years previously,
when the one on
the left was
hypophysectomiz
ed.
Effect of growth hormone treatment for 4 days on
the proximal tibial epiphysis of the
hypophysectiomized rat.
Note that increased width of the unstained cartilage
plate in the tibia of the right, compared with the
control in the left.
Growth Hormone Excess
GRH + - SS
- -
Pituitary
GH
Liver
SM Target tissues
SECRETION
3. Synthesis and Release of Vasopressin (VP) and
Oxytocin (OXT)
Cells in neurohypophysis do not synthesize hormones
but act simply as supporting structure for nerve
fibers.
Vasopressin (VP), also called ADH, and oxytocin (OXT) are
initially synthesized in the cell bodies of the supraoptic and
paraventricuar nuclei of hypothalamus
and are transported down to the nerve endings in the
neurohypophysis by hypothalamic hypophyseal tract.
When nerve impulses are transmitted downward along the
fibers from nuclei, the hormone is immediately released from
secretary granules in the nerve endings by exocytosis and is
absorbed into adjacent capillaries.
(1) Roles of ADH
1) Antidiuretic effect (refer to chapter 8)
1) INCREASES WATER REABSOPTION FROM
DISTALTUBULE & COLLECTING DUCTS OF
KINEY
H2O2
Hydrogen Peroxide
Iodine attached to tyrosine within thyroglobulin
chain.
–Attachment of 1 iodine produces monoiodotyrosine
(MIT).
–Attachment of 2 iodines produces diiodotyrosine (DIT).
Within the colloid, enzymes modify the structure of
MIT and DIT and couple them together.
When two DIT molecules are coupled together, a
molecule of tetraiodothyronine, T4, or thyroxine, is
produced.
The combination of one MIT with one DIT forms
triiodythyronine, T3.
Thyroid Hormone Synthesis:
3’ 3
5’ 5
DIT
Hypothyroidism
2) On carbohydrate metabolism
A: Increase absorption of glucose from the
gastrointestinal tract
E: Enhance glycogenolysis, and even enhanced
diabetogenic effect of glucagon, cortisol and growth
hormone.
C: Enhancement of glucose utilization of peripheral
tissues.
3) On fat metabolism
Thyroid hormones accelerate the oxidation of free
fatty acids by cells and increase the effect of
catecholamine on decomposition of fat.
Thyroid hormones not only promote synthesis of
cholesterol but also increase decomposition of
cholesterol by liver cells.
The net effect of T3 and T4 is to decrease plasma
cholesterol concentration because the rate of synthesis
is less than that of decomposition.
2. Effect of Thyroid Hormones on Growth and
Development
Thyroid hormone is essential for normal growth and
development especially skeletal growth and development.
Thyroid hormones stimulate formation of dendrites,
axons, myelin and neuroglia.
A child without a thyroid gland will suffer from critinism,
which is characterized by growth and mental retardation.
Without specific thyroid therapy within three months after
birth, the child with cretinism will remain mentally
deficient throughout life.
3. Effects of Thyroid Hormone on Nervous System
Thyroid hormones increase excitability of central
nervous system.
The hypothyroid
individual is to have
fatigue, extreme
somnolence, poor
memory and slow
mentation.
4. Other Effects of Thyroid Hormone
(1) Effect on cardiovascular system
Thyroid hormones have a significant effect on cardiac
output because of increase in heart rate and stroke
volume, (may through enhance calcium release
from sarcoplasmic reticulum).
(2) Effect on gastrointestinal tract
Thyroid hormones increase the appetite and food
intake by metabolic rate increased.
Thyroid hormones increase both the rate of secretion
of the digestive juices and the motility of the
gastrointestinal tract.
Lack of thyroid hormone can cause constipation.
IV Regulation of Thyroid Hormone Secretion
1. Hypothalamic
Pituitary Thyroid Axis
(1)Effect of TSH
1)Increase secretion of T4 and
T3 by proteolysis of
thyroglobulin
2) Increase synthesis of thyroid
hormones
• zona glomerulosa
- secretes aldosterone
• zona fasciculata
- secretes glucocorticoids
• zona reticularis
- secretes androgens
Hormones of the Adrenal Cortex
C=O
OH
HO
testosterone cortisol
“moon face”
striae
CORTISOL
AND
FOODSTUFF
METABOLISM
4) Effects on water and electrolytes
Cortisol has a slight effect on enhancement of sodium
reabsorption and potassium excretion by distal tubules
and colleting ducts in kidney.
It increases the rate of renal blood flow and then
glomerular filtration rates, facilitating water
excretion.
In patients with adrenal insufficiency, excretion of
water is so slow that there is a danger of water
intoxication and only glococorticoids can repair this
deficit.
(2) On blood cells@@@
Cortisol increase the production of red cells and
platelets by stimulating bone marrow.
Cortisol decrease the number of lymphocytes and
eosinocytes because it causes atrophy of the all
lymphoid tissues and promotion of destruction of
lymphocytes and eosinocytes.
(3) On cardiovascular system
Glucocorticoids are necessary for maintenance of
normal blood pressure. There are three mechanisms
at least.
1) Cause permissive action, enhancing the response of
vascular muscle to catecholamines.
2) Inhibit synthesis of prostaglandins that have
vasodilator effect.
3) Reduces the permeability of capillaries, which is
useful to maintenance of blood volume.
(4) Effect on stress.
Almost any type of stress, whether physical or
neurogenic, will cause increase in ACTH secretion,
and consequent cortisol secretion. This increase is
essential for survival.
(5) Other effects.
Glucocorticoids also have many other effects such as:
increase in production of HCl and pepsin,
promotion of synthesis of fetal surfactant.
Glucocorticoids have pharmacological effects
including anti-inflammatory, antiallergic and
antishock effect.
2. Regulation of Secretion of Adrenocortical Hormone
Hypothalamus –
Anterior Pituitary
– Adrenocortical
Axis
(1) Action of ACTH:
Cortisol secretion
is almost entirely
controlled by
ACTH
(adrenocorticotro
pin hormone)
ACTH causes formation of
adrenocortical hormones by
increasing cAMP as a second
messenger and activates steps for
controlling adrenocortical
secretion.
Long-term stimulation of the
adrenal cortex by ACTH not only
increases secretory activity but also
causes hypertrophy and proliferation
of the adrenocorticol cells,
especially in the zona fasciculata
and zona reticularis, where cortisol
and androgens are secreted.
(2) CRH (corticotropin releasing
hormone)
A, Action of CRH
The action of CRH is to promote
synthesis and release of ACTH in
the cells of anterior pituitary
gland.
B, Regulation of CRH secretion
CRH is secreted in irregular bursts
throughout the day and plasma
ACTH and cortisol tends to rise
and fall in response to these
bursts.
Fluctuations in plasma ACTH and glucotorticoids
throughout the day in a normal girl (age 16).
The
circadian
rhythm is
driven by
impulses
from the
supra-
chiasmatic
nuclei
Any type of stress can
lead to enhance
secretion of CRH
through afferent nerve
pathways on
hypothalamus.
Consequently, ACTH
secretion increases and
cortisol concentration
becomes very high in
the blood.
CRH secretion is
inhibited by cortisol via
a feedback mechanism
(3) Feedback
mechanism
Cortisol has direct
negative feedbacks on
the hypothalamus to
decrease formation of
CRH
High circulating
levels of cortisol
inhibit secretion and
formation of ACTH,
decreasing response
of anterior pituitary
gland to CRH.
High levels of ACTH
also inhibit CRH
secretion by a negative
feedback mechanism.
These feedbacks help
regulate the plasma
concentration of cortisol
toward a normal control
level.
Clinical treatment of cortisol (large does and long time)
always cause the atrophy of the adrenal gland. Please describe
the mechanism.
Section 5 Parathyroid Gland, Vitamin D and Parafollicular Cells
Self-study