The Endocrine System

Dr.Abu-zaiton
 Introduction
• The major communication systems in the body‫׳‬s
are:
Endocrine system.
Nervous system.
• The endocrine system consists of endocrine glands
(or ductless glands) that secrete hormones into the
extra cellular fluid, from which they diffuse into the
blood.
 Introduction
• Hormones are chemical messengers that enter the
blood, which carries them from endocrine glands to
the cells upon which they act.

• The cells influenced by a particular hormone are the

target cells for that hormone.
 Principles of Hormonal Control Mechanisms
Hormone Structures

• Hormones fall into three chemical classes:

1. Amines.
2. Peptides and proteins.
3. Steroids.
 1. Amine Hormones
• The amine hormones are all derivatives of the amino acid
tyrosine.
• e.g. Thyroid hormones that secreted from thyroid gland.

The two molecules differ

by only one iodine atom.

Theses hormones
control metabolic rate,
growth, and brain
development and function.
 1. Amine Hormones
• Adrenal medulla secretes two amine hormones, epinephrine
(E) and norepinephrine (NE).
• These molecules refer to chemical family of catecholamines.
 2. Peptide and protein hormones
• Most hormones are either peptides or proteins (all these
hormones are refers to as peptide hormones).

• During their synthesis; many protein hormones undergo

modifications during packaging and after they have been
secreted, e.g.,

pre-pro-insulin  pro-insulin  insulin

 3. Steroid Hormones:
• Steroid hormones are primarily produced by the adrenal cortex
and gonads (testes and ovaries) as well as by the placenta
during pregnancy.

• Cholesterol is the precursor of all steroid hormones.

• Steroids are highly lipid-soluble, once they are synthesized they

simply diffuse across the plasma membrane of the steroid-
producing cell.
 Hormone Transport in the Blood
i. Most peptide and all catecholamine hormones are water-
soluble.
 These hormones are transported simply dissolved in plasma.
ii. The poorly soluble steroid hormones and thyroid hormones
circulate in the blood largely bound to plasma proteins.
 Small concentrations of these hormones do exist dissolved in the
plasma.
 The dissolved, or free, hormone is in equilibrium with the bound
hormone:
Free hormone + Binding protein  Hormone-protein
complex
 Hormone Transport in the Blood

• Thus, the total hormone concentration in plasma is the sum of

the free and bound hormone.

• Only free hormone can diffuse across capillary walls and

encounter its target cells.
Therefore, the concentration of the free hormone is
physiologically important.
 Mechanisms of Hormone Action
Hormone Receptors:

• Because hormones are transported in the blood, hormones can

reach virtually all tissues.

• The response to a hormone is highly specific, involving only the

target cells for that hormone.

• The ability to respond depends upon the presence on (or in) the
target cells of specific receptors for those hormones.
 Mechanisms of Hormone Action
Hormone Receptors:
• Peptide hormones and catecholamines receptors are proteins
located in the plasma membrane of the target cells.
 Since these hormones are too large and hydrophilic to diffuse through
the plasma membrane.
 When the receptors are activated by hormone binding, the receptors
trigger one or more of the signal transduction pathways that lead to
generate second messengers.
 The second messenger alters some aspects of cell‫׳‬s functions, such as
change in enzymes activity (The effect of hormone in this case is rapid
action).
 Also, it may activate or inhibit genes causing a change in the rate of
synthesis of the proteins coded for by these genes (The effect of
hormone in this case is delayed action).
Hormone + Receptor
 Mechanisms of Hormone Action
Hormone Receptors:
• Steroid hormones and the thyroid hormones receptors are
proteins located mainly inside the target cells.
 Binding of hormone to one of these receptors leads to the activation (or
in some cases, inhibition) of the transcription of particular genes,
causing a change in the rate of synthesis of the proteins coded for by
those genes.
 Some target cells also have plasma-membrane receptors in addition to
having intracellular receptors.
 In such cases, the signal transduction pathways initiated by the plasma-
membrane receptors elicit rapid responses.
 The intracellular receptors mediate a delayed response.
 Mechanisms of Hormone Action
Hormone Receptors:
• Hormones can influence the ability of target cells to respond
by regulating hormone receptors.
i. Up-regulating: is an increase in the number of hormone‫׳‬s receptors,
often resulting from a prolonged exposure to a low concentration of
the hormone.
 This has the effect of increasing target cell responsiveness to
the hormone.
ii. Down-regulation: is a decrease in receptor number, often from
exposure to high concentrations of the hormone.
 This decreases target cell responsiveness to hormone, thus
preventing over-stimulation.
 Mechanisms of Hormone Action
Hormone Receptors:
• Permissiveness: the facilitation of the action of one hormone by another.
• e.g. The effects of epinephrine are exacerbated by thyroid hormone.

Thyroid hormones have a “permissive role” in the fat-mobilization response to

epinephrine.
 Inputs That Control Hormone Secretion
• Most hormones are secreted in short bursts, with little or no
release occurring between bursts.

• Therefore, plasma concentrations of hormones may fluctuate

rapidly over brief time periods.

• Hormones may also manifest 24-hour cyclical variations in their

secretory rates.
e.g. The secretion of growth hormone is increased
during the early period of sleep and is low during the
rest of the day and night.
 Inputs That Control Hormone Secretion
• Hormone secretion is controlled mainly by three types of inputs
to endocrine cells:
 Changes in the plasma concentrations of mineral ions or organic
nutrients.
 Neurotransmitters released from neurons impinging on the endocrine
cell.
 Another hormone or neurohormone (or, in some cases, a paracrine /
autocrine agent) acting on the endocrine cell.
 1. Mineral Ions or Organic Nutrients
• A major function of the hormone is to regulate, in a negative-feedback manner,
the plasma concentration of the ion or nutrient controlling its secretion.
• e.g. Insulin secretion

Increased glucose levels in the

pancreas directly stimulate
secretion of insulin.

“Insulin targets” are cells that

have insulin-receptors.
 2. Control by Neurons:
• The autonomic nervous system has influences on endocrine
glands.

• Some are inhibitory and some stimulatory.

• e.g. Secretion of insulin and the gastrointestinal hormones.

• Hormones that secreted by the hypothalamus and posterior

pituitary are under direct control of neurons in the brain.
(a) Certain neurons in the hypothalamus, some of which terminate
in the posterior pituitary, secrete hormones.

(b) The autonomic nervous system controls hormone secretion by

the adrenal medulla and many other endocrine glands.
 3. Control by Other Hormones:
• The secretion of a particular hormone is directly controlled by
the blood concentration of another hormone.

• A hormone that stimulates the secretion of another hormone is

often referred to as a tropic hormone.

• The tropic hormones usually stimulate not only secretion but

also the growth of the stimulated gland.
e.g. TSH (Anterior pituitary)  Thyroid hormones (Thyroid)
 Inputs That Control Hormone Secretion
• Hormone secretion may be influenced by more
than one input.
• E.g. Insulin secretion is controlled by the
extracellular concentrations of glucose and also by
neurons acting on insulin-secreting endocrine cells.
• Thus, endocrine cells may be subject to multiple,
simultaneous, often opposing inputs, and the
resulting output- the rate of hormone secretion –
reflects the integration of all these inputs.
The Endocrine System
“Hormonal Control
Mechanisms”
Part II
Where are Hormones Made ?
 1. The Hypothalamus and Pituitary Gland

• The pituitary gland lies in the base of the brain, below the
brain area called the hypothalamus.
• The pituitary is connected to the hypothalamus by the
infundibulum.
• In human beings, the pituitary gland is composed of two
adjacent lobes:
– The anterior pituitary (toward the front of the
head; also called the adenohypophysis).
– The posterior pituitary (toward the back of the
head; also called the neurohypophysis).
 Posterior Pituitary
• The posterior pituitary is an outgrowth of the hypothalamus
and is neural tissue.
• The axons of two clusters of hypothalamic neurons pass down
the infundibulum and end within the posterior pituitary in close
proximity to capillaries and their terminals end directly on
capillaries.
• The hormones are not synthesized in the posterior pituitary
itself but in the hypothalamus, specifically in the cell bodies of
the hypothalamic neurons whose axon pass down the
infundibulum and end in the posterior pituitary.
• Stimuli (either hormones or neurotransmitters) act to generate
action potentials in the neurons; these action potentials trigger
the release the hormone by exocytosis.
• The hormone then enters the capillaries to be carried away by
the blood, thus, the posterior pituitary can modify the function
of far distant organs.
 Posterior Pituitary

The two posterior pituitary hormones are:

1. Oxytocin:
 Acts on smooth muscle cells in the breast to stimulate
milk secretion during lactation, and on uterine smooth
muscle to stimulate uterine contractions during labor.
 Its function in males are uncertain.
 Posterior Pituitary

2. Vasopressin (antidiuretic hormone (ADH)):

 Acts on smooth muscle cells around blood vessels to
cause muscle contraction, which results in constriction
of blood vessels and an increase in blood pressure.
 Also acts within the kidney to decrease water excretion
in the urine, thus retaining fluid in the body and helping
to maintain blood volume.
 Anterior Pituitary Hormones and the
Hypothalamus
• The hypothalamus connected with
anterior pituitary by an unusual
blood vessels connection.
• The capillaries at the base of the
hypothalamus recombine to form
the hypothalamo-pituitary portal
vessels.
• The hypothalamo-pituitary portal
vessels pass down the stalk
connecting the hypothalamus and
pituitary and enter the anterior
pituitary.
 Anterior Pituitary Hormones and the
Hypothalamus
Thus, the hypothalamo-pituitary portal vessels offer a
local route for blood flow directly from the
hypothalamus to the anterior pituitary.
This offers the advantage of a rapid response, and
minimizes the amount of hypothalamic hormone that
must by synthesized to reach an effective blood
concentration.

• Hypothalamic neurons secrete hormones that control the

secretion of all the anterior pituitary hormones.
• These hypothalamic hormones are collectively termed
hypophysiotropic hormones.
 Anterior Pituitary Hormones and the
Hypothalamus
• With one exception (Prolactin), each of the
hypophysiotropic hormones is the first in a
three-hormone sequence:
1. A hypophysiotropic hormone controls the
secretion of
2. an anterior pituitary hormone, which
controls the secretion of
3. a hormone from some other endocrine
glands, the last hormone then acts on its
target cells.

• This sequence of hormones offers:

1. They permit a variety of important
hormonal feedbacks.
2. They also allow amplification of a response
of a small number of hypothalamic neurons
into a large peripheral hormonal signals.
 Hypophysiotropic Hormones:

• The neurons in the hypothalamus secrete

the hypophysiotropic hormones around the
hypothalamo-pituitary portal vessels.
• Hypothalamic hormones enter the capillaries
and are carried by the hypothalamo-
pituitary portal vessels to the anterior
pituitary.
• If a cell has an appropriate receptor for a
given hypophysiotropic hormone, that cell
will respond by increasing or decreasing the
secretion of its pituitary hormone.
• The pituitary hormone then diffuse into the
same capillaries that delivered the
hypophysiotropic hormone.
 Hypophysiotropic Hormones:
• Each hypophysiotropic hormone is named for the anterior pituitary
hormone whose secretion it controls.
• e.g. secretion of growth hormone is stimulated by growth hormone-
releasing hormone (GHRH).
Somatostatine Dopamine
Overview of Anterior Pituitary Hormones:
 Overview of Anterior Pituitary Hormones:
• Six of the well-characterized hormones secreted by the
• anterior pituitary gland and their targets are represented;
• all six hormones are proteins.
• Relationships between hypothalamic, pituitary, and
• third-gland hormones or other targets are shown.
Neural Control of Hypophysiotropic Hormones

• Neurons of the hypothalamus receive synaptic

input, both stimulatory and inhibitory, from
virtually all areas of the central nervous system, and
specific neural pathways influence the secretion of
the individual hypophysiotropic hormones.
 Hormonal Feedback Control of the Hypothalamus
and Anterior Pituitary

• A prominent feature of each of the

hormonal sequences initiated by a
hypophysiotropic hormone is
negative feedback exerted upon the
hyopthalamo-pituitary system by
one or more of the hormones in its
sequence.
• Long-loop negative feedback: The
hormone secreted by the third
endocrine gland in a sequence
exerts a negative feedback effect
over the anterior pituitary and/or
hypothalamus.
 e.g. The CRH-ACTH-cortisol
sequence.
 Hormonal Feedback Control of the Hypothalamus
and Anterior Pituitary

• Short-loop negative feedback:

influence of hypothalamus by an
anterior pituitary hormone.
 e.g. Negative feedback in the
prolactin system, for this hormone
itself acts upon the hypothalamus to
stimulate the secretion of
dopamine, which then inhibits the
secretion of prolactin.
 e.g. Growth hormone.
How Does Hypersecretion of GH
Happen?
 2. The Thyroid Gland

• The thyroid gland is a

bilobed structure that
sites within the neck
straddling the trachea.

• It first becomes
functional early in fetal
life, consistent within its
important actions on the
development of brain
cells.
 Actions of Thyroid Hormones:
• Thyroid hormones are made by attaching iodine (I -) molecules
to the amino acid tyrosine
• T3 and T4 are lipid soluble and diffuse out of the follicles into
the blood where another protein thyroxine-binding globulin
(TBG) picks them up and transports them to where they are
needed.
• Thyroid hormones (TH) receptors are present in the nuclei of
most of the cells of the body.
 Thus, the actions of T3 and T4 are widespread and affect many
organs and tissues.
• T3 and T4 act by inducing gene transcription and protein
synthesis.
• Although both T3 and T4 enter the blood stream, most of the
T4 is converted to the more active form T3 by the time it
reaches target cells.
Thyroid Gland Hormones
 Function of Thyroid Hormones

1. Metabolic Action:
• Thyroid hormones have several effects on carbohydrate and lipids metabolism.
 TH stimulates carbohydrate absorption from the small intestine.
 TH increases fatty acid release from adipocytes.
2. Growth and Development:
• TH are essential for normal growth because they are required
for both the synthesis of growth hormone and the growth-
promoting effects of that hormone.
• Therefore, in the absence of TH, growth in children is
decreased.
 Clinical Problems
Hypothyroidism:
• Any condition characterized by plasma levels of TH that are
chronically below normal.
• One form of this condition that exists around the world is due
to iodine deficiency.
• In adults, it causes decreased metabolic rate that can lead to a
condition called myxedema. Symptoms include slow heart beat,
low body temperature, dry skin, tiredness, and edema.
Hyperthyroidism
• Abnormally high secretion of thyroid hormones
• symptoms include increased body metabolism, increased food
consumption, heat intolerance, insomnia, nervousness, and
sweating.
 Clinical Problems
Cretinism:
• During the fetal life, TH exerts many effects on central nervous
development, including the formation of nerve terminals and the
production of synapses, the growth of dendrites and dendritic
extensions, and the formation of myelin.
• Absence of TH during fetal life results in a poorly developed nervous
system and a form of mental retardation called cretinism.
• The most common cause of cretinism around the world is dietary
iodine deficiency in the mother.
• If the condition is discovered and corrected with iodine and TH
administration shortly after birth, the mental and physical
retardation can be prevented.
Hypersecretion of TSH or TH
Goiter
Hyposecretion of TH
 Other hormone secreted by Thyroid
Gland
• Scattered among the follicular cells of the
thyroid follicles are parafollicular cells that
secrete a hormone, called calcitonin.
• Lowers serum calcium levels in the blood by
inhibiting bone breakdown by osteoclasts and
stimulating the movement of calcium into
bones
 3. The Adrenal Glands

• They are two adrenal

gland, one on the top
of each kidneys.
• Each adrenal gland
comprises two distinct
endocrine glands:
 An inner adrenal medulla,
which secrets amine
hormones.
 A surrounding adrenal
cortex, which secrets
steroid hormones.
Adrenal Gland Hormones
 The Adrenal Glands and the Response to
Stress
1. Physiological functions of cortisol:
• Cortisol is released from the adrenal cortex upon stimulation
with ACTH, which in turn, is stimulated by the release of
corticotrophin-releasing hormone (CRH) from the
hypothalamus.
• The physiological functions of cortisol are:
 Cortisol maintains the responsiveness of target cells (e.g. muscle cells
that surround blood vessels) to epinephrine and norepinephrine. Thus,
cortisol maintains normal blood pressure.
 Anti-inflammatory.
 Anti-immune functions to provide a "check" on the immune system.
 To promote normal differentiation of tissues during fetal life.
 The Adrenal Glands and the Response to
Stress
Functions of Cortisol in Stress:
 Cortisol secretions increase in response to stress.
 Clinical Problems

• The increased blood levels of cortisol in the nonstressed individual

tend to promote uncontrolled catabolism of bone, muscle, skin,
and other organs.
 Combined with an increased appetite, which is often triggered by
high concentrations of cortisol, this results in obesity and a
characteristics facial appearance in many patients.
 Hypertension.
 Epinephrine
• Cells of the adrenal medulla produce, store and release large amounts of
catecholamines: epinephrine and norepinephrine.
• Both hormones are synthesized from tyrosine (amino acid) with epinephrine
present in higher concentration. Epinephrine is also called adrenaline, and
norepinephrine is also called noradrenaline.
– Stressful events are perceived by the hypothalamus and the sympathetic nerve
impulses carry the "message" directly to the adrenal medulla
– Epinephrine prepares the body for "flight or fight"
– Blood glucose rises
– Blood flow is directed to skeletal muscle and away from digestive area
– Heart rate increases
– Blood pressure rises
– Rate of respiration increases
– Bronchioles dilate
 Norepinephrine
• Norepinephrine or noradrenaline is a catecholamine with dual
roles as a hormone and a neurotransmitter.
• As a stress hormone, norepinephrine affects parts of the brain
where attention and responding actions are controlled.
• Along with epinephrine, norepinephrine also underlies the
fight-or-flight response, directly increasing heart rate, triggering
the release of glucose from energy stores, and increasing blood
flow to skeletal muscle
• Serotonin-norepinephrine reuptake inhibitors are
antidepressants that treat depression by increasing the amount
of serotonin and norepinephrine available to postsynaptic cells
in the brain
Endocrine Control of Growth
Summary Of The Hormones
Summary Of The Hormones
Summary Of The
Hormones