The Endocrine System

Ahmed Al-Dwairi, PhD

The Endocrine System
 The Endocrine System
• The endocrine system consists of the ductless glands and their hormones.

• The endocrine system is involved in all of the integrative aspects of life,

including growth, sex differentiation, metabolism, and adaptation to an ever-
changing environment.

• The endocrine system participates in the regulation of digestion and the usage
and storage of nutrients, growth and development, electrolyte and water
metabolism, and reproductive functions.

• The endocrine system regulates the internal milieu of an animal

(homeostasis ).

• Target cells are specific for each hormone as these cells have receptors that
uniquely bind to a specific chemical messenger

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 Classes of Chemical Messengers

• Neurotransmitters: released by axon terminals of neurons into the synaptic junctions and act locally to control nerve cell functions.

• Endocrine hormones: released by glands or specialized cells into the circulating blood and influence the function of cells at another
location.

• Neuroendocrine hormones: secreted by neurons into the circulating blood and influence the function of cells at another location in the
body.

• Paracrines: secreted by cells into the extracellular fluid and affect neighboring cells of different type.

• Autocrines: secreted by cells into the extracellular fluid and affect the function of the same cells that produced them.
ENDOCRINE VS. NERVOUS SYSTEM
 Mechanisms of Hormone Action
 The first step of a hormone’s action is to bind to specific receptors at the
target cell.
o Hormonal receptors: are large proteins, and each cell that is to be
stimulated usually has some 2000 to 100,000 receptors, also., each
receptor is usually highly specific for a single hormone.
o Target tissue: the target tissues that are affected by a hormone are those
that contain its specific receptors.

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 Hormone Levels & Tissue Responses

• Priming effect (up regulation)

o The cells of the body increase the number of receptors to a
certain hormone (when there is low concentration of this
hormone)
o Results in greater response in target cell

• Desensitization (down regulation)

o The cells of the body decrease the number of receptors to a
certain hormone (when there is high concentration of this
hormone)
o Results in weaker response in target cell
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 Hormone Plasma Levels
• The plasma concentrations of many hormones
fluctuate in response to various stimuli that occur
through out the day, and appeared to be closely
controlled .

• To ensure a proper level of hormone activity at the

target tissue.

• Balance between:
– Rate of secretion & Rate of excretion 9
 Hormone Clearance
1. Metabolic destruction by the tissues (enzymes).
2. Binding with the tissues.
3. Excretion by the liver into the bile (mainly steroid
hormones).
4. Excretion by the kidney into the urine (peptide
hormones & catecholamines).

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 HORMONE EXCRETION
1. Hydrophilic hormones
• Dissolved in plasma, not bound to plasma proteins
• Rapidly eliminated from circulation, short half life.

2. Lipophilic hormones
• Circulate in the blood mainly bound to plasma proteins.
• Binding slows hormone clearance from plasma, long half life

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Half-life is the time required for blood level of a hormone to be
reduced by half
 Mechanisms Controlling Hormone Secretion

1. Negative-feedback control
2. Positive-feedback control
3. Neuroendocrine reflexes
4. Diurnal (circadian) rhythms

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 Mechanisms Controlling Hormone Secretion
1- Negative feedback prevents over activity of hormones systems:

 After stimulus causes

release of the
hormone ,conditions
or products resulting
from the hormone
tend to suppress its
further release.

 In other words , the

hormone (or one of its
products ) has a
negative feedback
effect to prevent over
secretion of hormone
or over activity at the
target tissue

 Can occur at all levels;

gene transcription,
translation,
processing and 13
releasing steps.
 Mechanisms Controlling Hormone Secretion
2- Surges of hormones
can occur with positive
feedback :

The biological action of

hormone causes additional
secretion of the hormone.

 One example is the

surge of luteinizing
hormone(LH) that
occurs as a result of the
stimulatory effect of
estrogen on the
anterior pituitary
before ovulation.
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 Mechanisms Controlling Hormone Secretion

3 - Neuroendocrine reflexes:
 Sensory stimulus
(e.g., suckling)
evokes a neural
pathway that leads
to secretion of a
hormone

 To produce a
sudden increase in
hormone
secretion
 Mechanisms Controlling Hormone Secretion
4- Cyclical variations occur in hormone release :
 Seasonal changes (gonadal hormones)
 Various stages of development and aging (GH, gonadal hormones)
 The diurnal (daily) cycle and sleep (cortisol, GH)

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Mechanisms of hormone action

1. Change of membrane permeability

2. Activation of intracellular enzyme
3. Binding with intracellular receptors,
stimulation / inhibition of gene
transcription
 Adenylate Cyclase-cAMP System

 Hormone binds to receptor

protein causing dissociation of
 subunit from G-protein
complex.

 G-protein  subunit binds to

and activates adenylate cyclase.

 ATP  cAMP + PPi

 cAMP activates protein kinase.

 Protein kinase phosphorylates

enzymes within the cell to
produce hormone’s effects
(activates or inhibits other
enzymes).

 cAMP inactivated by
phosphodiesterase. 18
Hypothalamic-Pituitary
Relationship

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•
The Pituitary Gland (Hypophysis)
Lies in sella turcica, a bony cavity at the base of the brain.
• Connected to the hypothalamus by the pituitary stalk (or infundibulum).
• The master gland

adenohypophysis

neurohypophysis
 The Anterior Pituitary
Embryologically: Derived from a pouch of
epithelial tissue (Rathke’s pouch), which is
derived from pharyngeal epithelium (mouth).

Histologically: Contains many types of secretary

cells (Chromophils):

Acidophils (epsilon )
Somatotropes – (GH)  30-40%
Lactotropes – (PRL)  3-5%

Basophils (delta )

Corticotropes – (ACTH)  20%

Thyrotropes – (TSH)  3-5%
Gonadotropes – (LH, FSH)  3-5%

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Anterior Pituitary Hormones
• Many are tropins
• Tropins or tropic hormones: hormones
that regulate the hormone secretions of
target endocrine tissues.
 The Posterior Pituitary

• Embryologically; derived from a down growth

of the hypothalamus.

• The neural part of the pituitary gland;

composed of pituicytes which support terminal
nerve fibers and endings descending from the
hypothalamus.

• In contact with the infundibulum &

adenohypophysis.

• The bodies of the cells that secrete the

posterior pituitary hormones are not located in
the pituitary gland itself but are large neurons,
called magnocellular neurons, located in the
supraoptic and paraventricular nuclei of the
hypothalamus.

• The hormones are then transported

(neurophysin carrier) in the axoplasm of the
neurons' nerve fibers passing from the
hypothalamus to the posterior pituitary gland.
 The Hypothalamus
 The hypothalamus is a collecting center for
information

 Receives signals from many sources in the nervous system

 Temperature regulation
 Control of food and water intake
 Projections to autonomic nervous system “head ganglion”
 Control of emotional expressions, sexual behavior

 Hypothalamus in turn controls the secretion of the pituitary hormones

Almost all secretions by the pituitary are controlled by

either hormonal or neural signals from hypothalamus
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Hypothalamus Controls Anterior Pituitary Secretion
Hypothalamus Controls Anterior Pituitary Secretion
Schematic diagram to explain anatomical and functional
relationship between the hypothalamus and pituitary gland

Hypothalamic neurons
synthesize oxytocin or
antidiuretic hormone (ADH)

Oxytocin and ADH are

stored in the axon
terminals.
When hypothalamic
neurons fire, action
potentials causes
hormone release into
the blood.

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 Growth Hormone (GH)
• Also called somatotropic
hormone or
somatotropin.

• Small peptide hormone

that contains 191 amino
acids in a single chain,
MW 22,005Da.

• Has great effect in

growth & metabolism.

• In contrast to other
hormones, it does not
function through a target
gland but exerts its
effects directly on all or
almost all tissues of the
body.
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 Actions of GH
Increasing the number of cells
1. Growth-promoting (hyperplasia)
stimulating cell division
actions on: preventing apoptosis

Increasing the size of cells (hypertrophy)

 Soft tissues stimulates synthesis of proteins
inhibits protein degradation
promotes the uptake of amino acids by cells

 Skeleton

2. Metabolic actions

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 Somatomedins
 Growth Hormone Exerts Much of Its growth-promoting Effect indirectly Through Intermediate
Substances Called "Somatomedins“

 Somatomedins are referred to as insulin-like growth factors (IGF); peptide hormone homologous to
proinsulin, Effects on growth are similar to effects of insulin on growth (so called Insulin-like Growth
Factors or IGFs)

 At least four somatomedins have been isolated, most important

of these is somatomedin C (IGF-I), its concentration in the plasma
closely follows the rate of growth hormone secretion.

 The major source of circulating IGF is the liver, also produced

locally by most other tissues.

 IGF synthesis is stimulated by GH

Growth 31
 GH has short half life (≈20 min.) while somatomedins have long
half life (≈ 20 h), carrier protein in blood.
 Growth Hormone Deficiency

 In childhood; results in dwarfism:

 short stature
 poorly developed muscles (reduced muscle-protein
synthesis)
 excess subcutaneous fat (less fat mobilization).

 In adulthood; relatively few symptoms:

 reduced skeletal muscle mass and strength (less muscle
protein)
 decreased bone density (less osteoblast activity during
ongoing bone remodeling).

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 Growth Hormone Excess
 In childhood before the epiphyseal plates close,
gigantism :
 rapid growth in height without distortion of body
proportions.

 After adolescence after epiphyseal plates close,

acromegaly :
 person cannot grow taller, but the bones can become
thicker (hands, feet, lower jaw…) and the soft tissues can
continue to grow
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Pancreatic hormones and
glucose homeostasis
 The Endocrine Pancreas
Islets of Langerhans

Exocrine portion

The endocrine hormones of the pancreas are produced in the Islets of Langerhans,
small islands or clusters of cells first described by Paul Langerhans in 1869
Insulin Synthesis and Secretion

• Insulin is a small protein; MW of 5808 kd.

• It is composed of two amino acid chains; A
& B with disulfide linkages in between.

• Preproinsulin (ER) proinsulin (Golgi)

insulin + C peptide (Secretory granules)

• Insulin and C peptide are secreted in

equimolar amounts

• Level of insulin is assessed by the level of

C- peptide
• Insulin plasma half-life ~ 6 minutes;
insulinase
How does insulin promote glucose uptake?
Insulin
Glucose
α α

P β β P GLUT-4
P P

IRS P
GLUT-4 Vesicle

Fat synthesis
Protein synthesis 37

Glycogen synthesis
Growth and gene expression
 Insulin Receptor
 Enzyme-linked tyrosine kinase receptor

 Tetramer made up of two α and two β glycoprotein

subunits
 Insulin binds to α subunits 
Autophosphorylation of β subunits 
Phosphorylation of IRSs (Insulin receptor substrates)
  Glucose uptake
 Major Target Tissues of Insulin

Glycogen

Glucose Glucose-P Glucose

Amino Pyruvate Free fatty

Acids CO2 acids
AdiposeTissue
Liver Ketoacids
↑ Glucose entry via GLUT4
 Gluconeogenesis ↑ Fatty acid synthesis
 Ketogenesis ↑ Triglyceride deposition
↑ Lipoprotein lipase activity
↑ Protein synthesis
↑ K+ uptake
Muscle ↑ Lipid synthesis
↑ Glucose entry via GLUT4
↑ Glycogen synthesis
Plasma
↑ Amino acid uptake  Glucose
↑ Protein synthesis  Free fatty acids
 Protein catabolism  Ketoacids
↑ Ketone uptake
↑ K+ uptake
 Amino acids
 Glucagon
 Polypeptide hormone secreted by α cells of the islets of
Langerhans
 Glucagon opposes the actions of insulin.
 Site of action: liver and adipose tissue.

 Secreted in response to:

 Fall in blood glucose concentration (Hypoglycemia).
 Amino acids in the blood. (conversion of amino acids into glucose)
 Exercise
 Fasting

 Hyperglycemic hormone

 Works through cAMP/PKA second messenger system 40

Thyroid Hormones

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 Structure of the Thyroid Gland

 Formed of 2 lobes (Rt & Lt) in the neck just below

the larynx, on either side of & anterior to the
trachea.

 Composed of large numbers of closed follicles

(the functional units)

 Follicles are filled with colloid (secretory

substance) and lined with cuboidal epithelial cells
(secrete into the interior of the follicles)

 The major constituent of colloid is thyroglobulin

(glycoprotein containing the thyroid hormones)

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 Thyroid Hormones

1. Triiodothyronine (T3)
2. Tetraiodothyronine or thyroxine (T4)
3. Calcitonin

Thyroid Hormone = Tyrosine +

Iodine
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 Thyroid Hormones
T3 & T4

 50 milligrams of iodine are required each year for the formation of adequate quantities of
thyroid hormone.

 Both are secreted from the Follicular cells

 Both can be stored in thyroid gland for couple of months

 Secretion: T4 >>> T3
 Peripherally: most T4 is converted into T3
 Activity: T3 >>> T4

 SO, T3 is the major biologically active form of thyroid hormone at the cellular level, even 44
though the thyroid gland secretes mostly T4.
Control of
Thyroid
Hormone
Secretion
 Thyroid Hormones
Calcitonin

 Important for calcium metabolism

 reduces blood Ca2+ – increases Ca2+ deposition in bone

 Secreted from Parafollicular cells (or C-cells)

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Effects of Thyroid Hormones (T3 & T4)
 Effect on metabolic rate and heat production:
 Increased metabolic activity (O2 consumption)
 Increased heat production (calorigenic)

 Sympathomimetic effect:
 Increase target cell responsiveness to catecholamines
 increase heart rate and the force of heart contraction.

 Effect on growth:
 stimulate GH secretion
 promote the effects of GH on the synthesis of new structural proteins and on skeletal growth

 Large amounts of the secreted hormone convert glycogen into glucose and
stimulates protein degradation.

 Effect on nervous system:

 Necessary for normal development
 Normal CNS activity in adults 47
 Abnormalities of Thyroid Function

 Hypothyroidism
 Hyperthyroidism
 Goiter

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 Abnormalities of Thyroid Function

Hypothyroidism: thyroid hormone deficiency

1. Cretinism : hypothyroidism from birth:

 Growth retardation
 Mental retardation

2. Myxedema: In severe cases, development of edematous

appearance throughout the body

 Symptoms: lowered basal metabolic rate,

excessive weight gain, bradycardia, cold
intolerance and the quick onset of fatigue.

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 Abnormalities of Thyroid Function

 Hyperthyroidism: thyroid hormone excess

Most common cause; Graves’ disease, body produces

thyroid-stimulating immunoglobulin (TSI) which targets
TSH receptors on thyroid cells

Symptoms: exophthalmos (bulging eyes), elevated

metabolic rate, high heart rate, heat
intolerance

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 Abnormalities of Thyroid Function

 Goiter

 Enlarged thyroid gland

 Becomes palpable and usually highly visible

 Occurs whenever either TSH or TSI excessively stimulates the

thyroid gland

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Adrenal Hormones

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Adrenal glands

Aldosterone
(Mineralocorticoid)

Cortisol
(Glucocorticoid)

Sex hormones
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Catecholamines
(Epinephrine+Norepinephrine)
 Aldosterone Effects
 Site of aldosterone action is on the distal and
collecting tubules of the kidney

 Promotes Na+ retention  osmotic H2O

retention  increased ECF volumes 
increased blood pressure

 Enhances K+ elimination
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REGULATION OF ALDOSTERONE SECRETION

Na+ deprivation

Decreased ECF volume Increase Plasma K+

Renin Angiotensin II

Aldosterone
 Aldosterone secretion is increased by:
 Activation of the renin-angiotensin system
 Direct stimulation of the adrenal cortex by a rise
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in plasma K+ concentration
 Cortisol Effects
 Metabolic effects
 stimulates hepatic gluconeogenesis
 inhibits glucose uptake and use by many tissues
 stimulates protein degradation in many tissues, especially muscle
 facilitates lipolysis
 Permissive actions
 permits the catecholamines to induce vasoconstriction
 Adaptation to stress

 Stress is one of the major stimuli for increased cortisol secretion

 Increased pool of glucose, amino acids, and fatty acids is available for use in stressful
situations
 Anti-inflammatory and immunosuppressive effects

 Pharmacological effect (at higher than normal concentrations)

 Suppresses the body’s response to the disease

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 Useful in allergic disorders and organ transplant rejections
 Highest in the
morning lowest at

Control of cortisol
night

secretion

o ACTH from the anterior

pituitary stimulates the
secretion of cortisol from the
adrenal cortex.

o ACTH secretion is triggered

by CRH from the
hypothalamus.

o Negative feedback from

cortisol in the blood to the
hypothalamus and the
anterior pituitary regulates
the level of cortisol in the
blood.
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Abnormalities of the Hormones of the
Adrenal Cortex

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 Aldosterone hypersecretion

• Causes:

E.g., Conn’s syndrome  hypersecreting adrenal tumor made

up of aldosterone-secreting cells (primary hyperaldosteronism )

The secondary hyperaldosteronism is due to the high activity of

the renin-angiotensin mechanism.
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 Cortisol hypersecretion
(Cushing’s syndrome)

• Due to increased amounts of CRH or ACTH, adrenal tumors, or

ACTH-secreting tumors. The main symptom of this condition is
excessive gluconeogenesis.

• mobilization of fat from the lower part of the body, with concomitant extra
deposition of fat in the thoracic and upper abdominal regions “buffalo hump”

• “moon face”

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 Adrenocortical insufficiency
o E.g., addison’s disease: autoimmune destruction of the cortex
by production of cortex–attacking antibodies, affect all layers
and so all cortical hormones

o Symptoms: hypotension, hypoglycemia, potassium retention

and sodium depletion. There is poor response of the subject to
stress and hypoglycemia

pituitary or hypothalamic abnormality

affects cortisol only
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