ENDOCRINE SYSTEM
Dr. Othman Al-Shboul
Department of Physiology & Biochemistry
1
College of Medicine
OUTLINE

Introduction to Endocrine System

Pituitary Hormones – Growth Hormone

Thyroid Hormones

Adrenal Hormones

Pancreatic Hormones

Hormonal Regulation of Ca++ metabolism
2
INTRODUCTION TO
ENDOCRINE SYSTEM
3
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.
4
THE ENDOCRINE SYSTEM


The endocrine system consists of the
ductless glands and their hormones.
The endocrine system regulates
the internal milieu of an animal
(homeostasis ).
The “internal secretions” were
liberated by one part of the body,
traveled via the bloodstream to
distant targets cells. Claude
Bernard, Circa 1854


Target cells are specific for each
hormone as these cells have
receptors that uniquely bind to a
specific chemical messenger
5
NERVOUS VS. ENDOCRINE SYSTEM
6
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)
7
o Results in weaker response in target cell
CLASSES OF HORMONES
i.
Hydrophilic (peptide hormones and catecholamines)
o
o
ii.
Peptide hormones are chains of amino acids
 Include ADH, GH, insulin, oxytocin, glucagon, ACTH, PTH
Catecholamines include norepinephrine & epinephrine
Lipophilic (steroid hormones and thyroid hormone)
o
Steroid hormones are lipids derived from cholesterol
 Include testosterone, estrogen, progesterone, aldosterone
and cortisol
8
CLASSES OF HORMONES
i.
Hydrophilic
o
o
o
Water soluble
Surface membrane receptors
Activate 2nd -messenger systems (cAMP, Ca++)
Hydrophilic Hormone
9
2nd Messenger
ADENYLATE CYCLASE-CAMP SYSTEM

Hormone binds to receptor protein
causing dissociation of  subunit from Gprotein 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.
Protein Kinase A
10
CLASSES OF HORMONES
ii.
Lipophilic
o
o
o
Lipid soluble
Cytoplasmic/nuclear receptors
Affect gene transcription
Lipophilic
Hormone
Gene Transcription
11
MECHANISM OF ACTION OF LIPOPHILIC
HORMONES VIA ACTIVATION OF GENES
12
13
HORMONE PLASMA LEVELS

Balance between:
Rate of secretion
&
Rate of excretion
14
MECHANISMS CONTROLLING HORMONE
SECRETION
1.
Negative-feedback control
2.
Neuroendocrine reflexes
3.
Diurnal (circadian) rhythms
15
1.
NEGATIVE-FEEDBACK CONTROL
• After stimulus causes release of
the hormone , the hormone (or
its products) tends to suppress
its further release.
• To maintain the plasma
concentration of a hormone at a
given level.
16
2.
NEUROENDOCRINE REFLEXES
• Sensory stimulus
(e.g., suckling) evokes
a neural pathway
that leads to secretion
of a hormone

Hypothalamus
Pituitary
Prolactin &
Oxytocin
To produce a sudden
increase in hormone
secretion
Spinal cord
17
3.


DIURNAL (CIRCADIAN) RHYTHMS
Repetitive oscillations in hormone levels that are very regular
and cycle once every 24 hours
Example, cortisol secretion, high in the early morning and low
at evening
18
HORMONE EXCRETION
i.
Hydrophilic hormones
o
o
Dissolved in plasma, not bound to plasma proteins
Rapidly eliminated from circulation, short half life.
ii. Lipophilic hormones
o Circulate in the blood mainly bound to plasma proteins.
o Binding slows hormone clearance from plasma, long
half life
Half-life is the time required for blood level of a
hormone to be reduced by half
19
PITUITARY HORMONES
20
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
Two Distinct Parts:
* The Anterior lobe
(adenohypophysis)
* The Posterior lobe
(neurohypophysis)
21
glandular
epithelial
tissue
nervous
tissue
HYPOTHALAMIC-PITUITARY RELATIONSHIP
Hypothalamus-anterior
pituitary
Hypothalamus-posterior
pituitary
vascular link
neural link
Factors (or hormones) released
from hypothalamus reach
anterior pituitary via circulation
Axons from hypothalamus extend
into posterior pituitary
22
I. POSTERIOR PITUITARY HORMONES
23
HYPOTHALAMUS & POSTERIOR PITUITARY
Posterior pituitary gland does
not synthesize hormones
Posterior pituitary gland
stores & releases hormones
that are generated &
secreted from hypothalamus
24
POSTERIOR PITUITARY HORMONES
1.
VASOPRESSIN (antidiuretic hormone, ADH)
2.
OXYTOCIN
25
VASOPRESSIN (ANTIDIURETIC
HORMONE, ADH)
 It
enhances the retention of H2O by the
kidneys (an antidiuretic effect), more
important
 It
causes contraction of arteriolar smooth
muscle (a vessel pressor effect, increasing
resistance)
26
OXYTOCIN
 Stimulates
contraction of the uterine smooth
muscle to help expel the infant during childbirth
 Promotes
ejection of the milk from the mammary
glands (breasts) during breast-feeding
Oxytocin is concerned with releasing or ejection of
milk, while prolactin (from the anterior pituitary) is
concerned with synthesis & production of milk.
27
II. ANTERIOR PITUITARY HORMONES
28
ANTERIOR PITUITARY HORMONES


Many are tropic hormones
Different cell populations within the anterior pituitary secrete six major peptide
hormones:
1.
Growth hormone (GH, somatotropin)
2.
Thyroid-stimulating hormone (TSH, thyrotropin), stimulates the secretion and growth
of the thyroid gland
3.
Adrenocorticotropic hormone (ACTH, adrenocorticotropin), stimulates the growth
and secretion of hormones from the adrenal cortex.
4.
Follicle-stimulating hormone (FSH), stimulates growth and development of the ovarian
follicles in females and sperm production in males.
5.
Luteinizing hormone (LH), stimulates ovulation and luteinization (female) and stimulates
testosterone secretion in the male.
6.
Prolactin (PRL), enhances breast development in females, milk productipon
29
Functions of the anterior
pituitary hormones
30
HYPOTHALAMIC HORMONES OR FACTORS


Secretion by the anterior pituitary is controlled by hormones called hypothalamic
releasing and hypothalamic inhibitory hormones (or factors) transported through
hypothalamic-hypophysial portal vessels
Hypothalamus receives signals from many sources in the nervous system & in
turn controls the secretion the pituitary hormones
31
HYPOTHALAMIC-HYPOPHYSEAL PORTAL SYSTEM
Venous blood flows
directly from one
capillary bed through
a connecting vessel to
another capillary bed
(without passing
through the heart).

32
GROWTH HORMONE (GH)
33
ACTIONS OF GH
i.
Metabolic actions
ii.
Growth-promoting actions on:

Soft tissues

Skeleton
34
ACTIONS OF GH
i.
Metabolic actions:
 Breakdown
of triglyceride fat stored in
adipose tissue  increased blood f.a levels
 Decreases
glucose uptake by muscles 
increases blood glucose levels
 Muscles
use f.a for energy, reserving glucose
for nervous tissue
35
ACTIONS OF GH
ii.

Growth-promoting actions on soft tissues
Increasing the number of cells (hyperplasia)



stimulating cell division
preventing apoptosis
Increasing the size of cells (hypertrophy)



stimulates synthesis of proteins
inhibits protein degradation
promotes the uptake of amino acids by cells
36
ACTIONS OF GH
Growth-promoting actions on skeleton
(bone)
iii.
1.
2.
Growth in bone thickness (stimulates osteoblasts
under periosteum)
Growth in bone length (stimulates osteoblasts at
epiphyseal plate)
Hyaline cartilage in growing bone (before puberty)
Plate/line (bone) in adults (after puberty)
37
SOMATOMEDINS


Growth hormone exerts its growth-promoting effects indirectly by
stimulating somatomedins.
Somatomedins are referred to as insulin-like growth factors
(IGF)

The major source of circulating IGF is the liver

IGF synthesis is stimulated by GH

IGF is also produced locally by most other tissues.
Growth
38
Increases after
the onset of
deep sleep
CONTROL OF
GH
SECRETION
Weak
Strong
39
ABNORMAL GROWTH-HORMONE SECRETION

GH Hyposecretion (deficiency)

GH Hypersecretion (excess)
40
GROWTH HORMONE DEFICIENCY
 In
childhood; results in dwarfism:



 In
short stature
poorly developed muscles (reduced muscle-protein
synthesis)
excess subcutaneous fat (less fat mobilization).
adulthood; relatively few symptoms:


reduced skeletal muscle mass and strength (less
muscle protein)
decreased bone density (less osteoblast activity
during ongoing bone remodeling).
41
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

42
THYROID HORMONES
43
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)
44
THYROID HORMONES
1.
Triiodothyronine (T3)
2.
Tetraiodothyronine or thyroxine (T4)
3.
Calcitonin
Thyroid Hormone = Tyrosine + Iodine
45
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
46

SO, T3 is the major biologically active form of thyroid hormone at the cellular
level, even though the thyroid gland secretes mostly T4.
THYROID HORMONES
Calcitonin
 Important for calcium metabolism
reduces blood Ca2+ – increases Ca2+ deposition in bone
 Secreted from Parafollicular cells (or C-cells)
47
THYROID HORMONES EFFECTS (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
48
CONTROL OF
THYROID
HORMONE
SECRETION
49
ABNORMALITIES OF THYROID FUNCTION

Hypothyroidism

Hyperthyroidism

Goiter
50
ABNORMALITIES OF THYROID FUNCTION

1.
2.

Hypothyroidism: thyroid hormone deficiency
Cretinism : hypothyroidism from birth:

Growth retardation

Mental retardation
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.
51
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
52
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
53
ADRENAL HORMONES
54
ADRENAL GLANDS
Aldosterone
(Mineralocorticoid)
Cortisol
(Glucocorticoid)
Sex hormones
55
Catecholamines
(Epinephrine+Norepinephrine)
ALDOSTERONE
56
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
57
REGULATION OF ALDOSTERONE SECRETION
Na+ deprivation
Increase Plasma K+
Decreased ECF volume
Renin
Angiotensin II
Aldosterone

Aldosterone secretion is increased by:

Activation of the renin-angiotensin
system

Direct stimulation of the adrenal cortex by
a rise in plasma K+ concentration
58
CORTISOL
59
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

Useful in allergic disorders and organ transplant rejections
60
CONTROL OF
CORTISOL
SECRETION
highest in the
morning
lowest at night
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.
61
ABNORMALITIES OF THE HORMONES OF THE
ADRENAL CORTEX
62
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.
63
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”
64
ADRENOCORTICAL INSUFFICIENCY
o
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
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
65
THE ENDOCRINE PANCREAS
66
ISLETS OF LANGERHANS
Somatostatin
Exocrine portion
(acinar & duct cells)
Glucagon
67
Insulin
INSULIN


Energy-giving foods in the diet, especially excess amounts
of carbohydrates increases insulin secretion
Insulin affects carbohydrate, fat, and protein metabolism
68
INSULIN ACTIONS


Actions on carbohydrates
o
Facilitates glucose transport into most cells
o
Stimulates glycogenesis (Glucose  Glycogen)
o
Inhibits glycogenolysis (Glycogen  Glucose)
o
Inhibits gluconeogenesis (amino acids  Glucose)
Actions on fat
o
Enhances the entry of fatty acids from the blood into adipose tissue cells for
storage as triglycerides

Actions on protein
o
Promotes transport of amino acids from the blood into muscles and other
tissues for protein synthesis
69
Lack of Effect of Insulin on Glucose
Uptake and Usage by the Brain
o
o
o
Most of the brain cells are permeable to glucose and
can use glucose without insulin
Brain cells use only glucose for energy
Hypoglycemic shock; progressive nervous irritability
that leads to fainting, seizures, and even coma
70
GLUCOSE TRANSPORT BETWEEN THE BLOOD AND CELLS

Glucose transporter (GLUT), Six forms (GLUT1-GLUT6)

Most important GLUT4 (skeletal muscle and adipose tissue cells)

GLUT4 is present on cell membrane upon insulin secretion only

Although skeletal muscles have GLUT4:

Resting  depend on insulin

Exercising  free from insulin dependence, good for diabetes mellitus
71
DIABETES MELLITUS
72
DIABETES MELLITUS
 The
most common of all endocrine disorders
 Due
to inadequate insulin action
 Types
o
o
lack of insulin secretion (type I)
decreased sensitivity of the tissues to insulin
(type II)
73
DIABETES MELLITUS
 The
most prominent features of diabetes mellitus
is elevated blood-glucose levels, or hyperglycemia
 Symptoms:
•
•
•
Polyphagia, excessive hunger and food
consumption
Polydipsia, excessive thirst
Polyuria, increased urine output
74
TYPES OF DIABETES MELLITUS
75
CONSEQUENCES OF




LOW INSULIN ACTIVITY
Glucosuria. Excess urination also occurs. This can lead
to circulatory failure, renal failure, and dehydration.
Increased lipolysis. Fatty acids are mobilized from
triglycerides. Liver use of fatty acids leads to ketosis.
Acidosis develops and can depress brain function.
Increased protein catabolism. This can reduce growth
and lead to the wasting of skeletal muscles.
Long-term complications of diabetes mellitus include
degenerative disorders of the vascular and nervous
systems.
76
GLUCAGON



In general, glucagon actions are opposite to those
of insulin
Secretion increases during the postabsorptive
state
Pancreatic α cells increase glucagon secretion in
response to a fall in blood glucose.

Catabolic effects on energy stores

The major site of action of glucagon is the liver
77
GLUCAGON ACTIONS

Carbohydrates:
Decreasing glycogen synthesis, promoting glycogenolysis, and
stimulating gluconeogenesis

Fat:
Promoting fat breakdown and inhibiting triglyceride synthesis

Proteins:
Inhibiting hepatic protein synthesis and promotes degradation
of hepatic protein, not muscle proteins
The growth hormone, cortisol, epinephrine,
and glucagon are insulin antagonists. They
increase blood glucose.
78
ENDOCRINE CONTROL
OF CALCIUM METABOLISM
79
REGULATION OF CALCIUM METABOLISM

Plasma Ca++ levels are under the regulation of three hormones:
o
o
o

Parathyroid hormone (from parathyroid glands)
Calcitonin (from thyroid gland)
Vitamin D
Regulation of Ca ++ metabolism depends on hormonal control of
exchanges between the ECF and three other compartments:
o
o
o
Bone
Kidneys
Intestine
80
DISTRIBUTION OF CALCIUM IN THE BODY
% Ca++
bone & teeth
intracellularly
extracellularly
Half of the plasma Ca ++ is bound to plasma proteins the
other half is free to leave the plasma and participate in
chemical reactions
81
IMPORTANCE OF CALCIUM



Neuromuscular excitability
Hypocalcemia (decreased blood Ca++)
 overexcitability
Hypercalcemia (increased blood Ca++)
 depressed neuromuscular
excitability
Affect
Na+
permeability
82
BONE (THE LARGEST CALCIUM RESERVOIR)
 Bone
continuously undergoes remodeling;
bone deposition (formation) and bone resorption
(removal) normally go on concurrently
[Osteoblasts vs. Osteoclasts]
 Mechanical
stress favors bone deposition
83
REGULATION OF CALCIUM METABOLISM
1.
Parathyroid hormone (from
parathyroid glands)
2.
Calcitonin (from thyroid gland)
3.
Vitamin D
84
1. PARATHYROID HORMONE (PTH)

Increases plasma Ca++ levels via:
o
o
o
Increasing bone resorption
Increasing kidney reabsorption
Increasing intestinal absorption (via
Vitamin D)
Chief (principal) cells secrete PTH

PTH also lowers phosphate ions in the blood.
85
REGULATION OF CALCIUM METABOLISM
Calcitonin (from thyroid gland)
2.

Lowers plasma Ca++ levels via increasing Ca++ deposition
in bone
Vitamin D
3.




Its synthesis is stimulated by PTH in the kidney
It increases plasma Ca++ levels mainly via increasing
intestinal absorption
Stimulates bone reabsorption.
86
Stimulates reabsorption of Ca++ and P043- by the kidney
VITAMIN D (OR CHOLECALCIFEROL)

Hormone or vitamin ?

Activation of vitamin D
PTH
87
THE END
88