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ENDOCRINE SYSTEM
OVERVIEW
BY
DR. SYED AFTAB OMAR
(MBBS, MD)
LEARNING OBJECTIVES
• Identify various aspects of neural & endocrine
regulation
• Describe the chemical nature of hormones and define
the terms preprohormone & prohormone
• Enlist overall hormonal functions
• Describe the different types of hormone interactions
and significance of hormone concentrations
• Explain the factors influencing the plasma
concentrations of hormones
• Identify the most common causes of endocrine
dysfunction
REGULATING SYSTEMS OF THE BODY
• Two major regulatory systems in the body,
• 1) Nervous system- coordinates rapid &
precise response and adjusts the body’s
interaction to external environment.
• 2)Endocrine system- controls activities
needing time rather than speed. Regulates,
coordinates & integrates cellular functions at a
distance.
Maintains homeostasis (internal environment)
ENDOCRINOLOGY
• Is the study of homeostatic chemical adjustments and
other activities of the body,
mediated by chemical substances known as
HORMONES.
-Term Hormone, derived from Greek phrase meaning,
(to set in motion)
- describes the dynamic actions of hormone
as they elicit cellular responses & regulate
physiologic processes by feedback mechanism
GENERAL PRINCIPLES
• Endocrine system:
• Is made up of ductless glands present
throughout the body
• Not connected with each other, but
functionally make a system
• Their function is carried out by hormones
secreted by each gland into the blood
• Hormones act on distant target cells
regulating or directing a particular function
ENDOCRINE GLANDS
Clumps or cords of secretary cells
surrounded by network of small
blood vessels
Hormones are poured directly into
blood
The signal chemicals are
• made in endocrine cells
• transported via blood
• receptors are on target cells
Exocrine Glands- Pour secretion
through duct system
Dual Glands- Endocrine/ Exocrine
functions – both are present e.g.,
Pancreas
Hormones – inter-cellular
communication molecules
Use chemical signals for cell to cell
communication
Coordinate the function of cells
Response to an endocrine signal
occur within minutes to hours
Neurotransmitters are chemicals
secreted by neurons that diffuse
across a small gap (synapse) to the
target cell. Neurons use electrical
signals as well.
Hormones secreted by neurons are
known as neurohormones. Thus
they have a neural origin. For
example (e.g.)
- Anti Diuretic Hormone (ADH)
- Oxytocin
Paracrine Horomones
• Site of synthesis & site of action
close together
• Act on adjacent cells
Autocrine Horomnes
Site of synthesis & effector (target)
same cell
Recurrent / Periodic Glands
• Appear & disappear according to
physiological demand
• e.g., Corpus Luteum & Placenta
Summary of endocrine system
• Endocrine system is made up of ductless glands
present in different part of the body
• Act by secreting hormones directly into blood
• Hormones reach target cells/organs by blood and
regulate and perform a particular function
• Hormones only act on specific target cells due to
presence of receptors
• Binding of hormones with receptors initiate a chain of
intracellular reactions
• Action of hormones depends whether it is hydrophilic
or lipophilic
Basic types of hormones
• Hormones are of two types;
1) Hydrophilic (water soluble)
-Peptide hormones
- Catecholamines
- Indoleamines
2) Lipophilic (fat soluble)
-Steroid hormones
-Thyroid hormones
CLASSIFICATION OF HORMONES
Classification of Hormones:
1. Proteins & Polypeptides
2. Steroids
3. Amino Acid tyrosine derivative
Proteins & Polypeptides
< 100 amino acids – peptide
> 100 amino acids – protein
Examples:
• Ant. & Post. Pituitary hormones
• Insulin / Glucagon
• Growth hormone
• Parathyroid hormone etc.
Steroids:
Are derived from cholesterol
have
Cyclopentanoperhydrophenanthrene nucleus
Example:
• Cortisol
• Aldosterone
• Testosterone
• Estrogen etc.
Amino Acid – tyrosine Derivatives
• Thyroid Hormones
• Epinephrine / Norepinephrine
HYDROPHILIC HORMONES
• A) Peptides: numerous, having a variable
chain of amino acids, secreted
from pituitary, pancreas
B) Catecholamine: derived from amino acid
tyrosine, secreted from
adrenal medulla
C) Indoleamine: derived from amino acid
tryptophan, produced from
pineal gland
LIPOPHILIC HORMONES
• 1)Steroid hormone: neutral lipids derived
from cholesterol,
produced by adrenal cortex
testis and ovaries
2) Thyroid hormone: is an iodinated tyrosine
derivative, secreted by
thyroid gland
HORMONE SYNTHESIS
• General principles of hormone synthesis:
A) peptide hormones:
In the cells of the endocrine glands, the
peptide molecule prepared first is usually
a larger precursor called as Preprohormone;
It is cleaved to form Prohormone;
Further cleavage of prohormone, forms the final
mature Hormone. e.g.
Preproinsulin → Proinsulin → Insulin
This hormone is stored in vesicles of endocrine cells and released on
demand.
B) Steroid hormones are synthesised from cholesterol: Once formed,
they are immediately released into circulation; they are not stored
Processing of Proinsulin
Connecting peptide
HOOC
NH2
20
1
1
S S
5
A-chain
B-chain
15
10
S
SS
5
30
S
25
10
20
15
Proinsulin
C-Peptide
S S
NH2
NH2
20
COOH
1
5
1
5
S
S
10
15
S
S
15
20
A-chain
Insulin
COOH
10
B-chain
25
30
Synthesis of peptide (hydrophilic)
hormones
Peptide hormones:
-produced & processed by endoplasmic
reticulum & Golgi complex
- stored in secretary vesicles
- release by exocytosis by special signals
- produce physiological response by binding
with membrane receptors of target cells
- act primarily by second messenger system
altering the activity of preexisting enzymes.
Catecholamine & Indoleamine: act similar to
peptide hormones
Synthesis & Secretion of
Peptide Hormones
LIPOPHILIC STEROID HORMONES
•
•
•
•
STEROID HORMONES:
Synthesis : is intracellular by step wise
modification from cholesterol
Steroid producing organs produce only
specefic hormone not all hormones due to
specefic enzymes needed for the steps
Act by combining intracellular receptors
THYROID HORMONES:
Thyroid hormones are produced by thyroid
Gland by a unique pathway
RELEASING & TROPIC HORMONES
Releasing hormones/ factors:
-is secreted by hypothalamus, acts on ant. pituitary to produce tropic
hormones e.g. GHRH, TRH,CRH,GNRH, PRH, SOMATOSTATIN
DOPAMINE
Tropic hormones:
- is produced by ant. Pituitary, regulate secretion and production of
another hormone by other endocrine gland e.g. TSH, ACTH, GH,
FSH, LH
-Thyroid stimulating hormone(TSH) from ant. Pituitary stimulates
thyroid gland to secrete thyroid hormones ie. thyroxin(T4) and
triiodothyronine(T3)
-Maintains the structure of thyroid gland.
- In absence of TSH , thyroid gland atrophies and produce low levels of
thyroid hormones.
TRANSPOT & STORAGE OF HORMONES
Transport: in combination with
- Globulin
- Albumin
-only 2 – 3% is in FREE FORM (biologically
active)
Storage
• Not usually stored – except
1. THYROXINE –by combining with
TYHYROGLOBULIN
2. INSULIN – can be stored in β – cells of
pancreas in complex form with Zinc
3. ADH – by combining with;
- Neurophysin – I
- Neurophysin – II
COMPLEXITY OF ENDOCRINE
FUNCTION
- Single endocrine gland produces many hormones e.g. Ant.
Pituitary ( 6 hormones)
- Single hormone may be secreted by more than one gland eg.
Somatostatin is secreted by hypothalamus and pancreas
- Single hormone may produce more than one effect e.g.
Vasopressin (ADH)
i)water reabsorption by DCT&CD by V2receptors
ii) Vasoconstriction of arterioles by V1 receptors
- Some hormone secretion varies over course of time in cyclic
pattern e.g. Control of menstrual cycle by sex hormones
- Single target cell (liver cells) may be influenced by more than one
hormone by activating different enzymes e.g.
Insulin; converts glucose into glycogen
Glucagon; converts glycogen into glucose
- Some chemical messenger may be hormone /neurotransmitter e.g.
Norepinephrine
- Some organs have exclusively endocrine function e.g.
Ant. Pituitary
- Some organs have both endocrine and non endocrine function e.g.
Testis produces testosterone and sperms
PLASMA CONCENTRATION OF
HORMONES
• Effective conc. of Hormone is influenced by:
- Hormone secretion
- Peripheral conversion e.g. T4 to T3
- Transported in free or in combined form
- Inactivation by enzymes
- Excretion by kidneys
• Effective plasma conc. of free, biologically active
hormone depends upon;
- Rate of secretion
- Rate of metabolic activation & conversion
in peripheral tissues e.g.
i) Thyroxin(T4) is converted to Triiodothyronine
(T3) which is more more potent
ii) Testosterone is converted to Estrogen by
enzyme aromatase
- Lipophilic hormones are bound to plasma proteins so free
hormone available is less to the tissues
- Rate of removal of Hormone;
-Hydrophilic hormones are easily inactivated by blood
& tissue enzyme. Remains in blood for (few
minutes to few hours)
-Lipophilic hormones are in bound form so less
vulnerable by enzymatic inactivation, remains
in blood for larger time few hours(steroids)
Weeks (thyroid hormone)
- Hormones are mainly eliminated by liver and kidneys.
Patients with liver & kidney disease may suffer from
excess of hormone activity
• Effective plasma conc. of hormone is
regulated by its rate of secretion
• Rate of secretion of hormone is not constant
by all the endocrine gland but depends on;
• i) Negative feed back control
• ii) Neuroendocrine reflexes
• iii) Diurnal (Circadian) rhythm
NEGATIVE FEED BACK CONTROL
HORMONAL REGULATION CONTD.
Modes of Hormonal
Regulation
(A) Feed back system
(B) Neural Control
(C) Chronotropic Control
(A) Feed back system
(Mainly)
- Negative Feed back
- Positive Feed back
i. Hormone – Hormone level
ii. Substrate – Hormone level
iii.Mineral – Hormone level
(B) Neural Control
i. Adrenergic
ii. Cholinergic
iii.Dopaminergic
iv.Serotinergic
v. GABAergic
(C) Chronotropic Control
i. Diurnal Rhythm
ii. Sleep – Wake Rhythm
iii.Menstrual Rhythm
iv.Seasonal Rhythm
v. Developmental Rhythm
vi.Circhoral Rhythm
vii.Ultradian Rythm
(C) Chronotropic Control
1. Diurnal Rhythm
- ↑ Prolactin secretion during night
2. Sleep Wake Rhythm
- Infants / Children – ↑ GH during sleep
- ↑ ACTH & ↑ Cortisol during sleep
3. Menstrual Rhythm
- ♀ reproductive life (15 – 45 yrs)
- Ovarian steroids – Estrogen & Progesterone
4. Seasonal Rhythm
- Esp. in lower animals (Frogs – Hibernate)
5. Developmental Rhythm
- eg., Growth Rythm
6. Circhorral Rhythm
- change on hourly basis eg., insulin after food
intake
7. Ultradian Rhythm
- moment to moment change eg., epinephrine
NEUROENDOCRINE REFLEXES
• Control system involve both neural &
endocrine factor eg.
• Secretion of epinephrine is controlled by
sympathetic nervous system
• Cortisol secretion is controlled both by
negative feedback and stress response
DIURNAL (CIRCADIAN) RHYTHM
• Secretion of hormone is not constant through
out the day e.g.
• Cortisol secretion rises during night, peak
secretion in early morning then falls during
the day
Some endocrine cycle work on time scale
e.g. monthly menstrual cycle not daily
Circadian Rhythm of Cortisol
INACTIVATION/CLEARANCE FROM
PLASMA
Inactivation / Clearance from
Plasma:
i. Metabolic destruction by tissues
ii. Binding with tissues
iii. Excretion by LIVER into BILE
- By conjugation with glucoronide
etc.
iv. Excretion by kidneys into urine
v. Skin
OVERALL FUNCTIONS OF ENDOCRINE
SYSTEM
• Wide ranging effects throughout the body:
• Regulating organic metabolism and water &
electrolyte balance thus maintaining
homeostasis
• Adaptive changes of body during stress
• Promoting growth & development of body
• Controlling reproduction
OVER ALL FUNCTIONS CONTD.
• Regulating RBC production (erythropoiesis)
• Along with autonomic nervous system(ANS)
regulate and integrate activities of CVS and
digestive system
ENDOCRINE DISORDERS
• Endocrine disorders result due to deficient
secretion (hypo secretion) or
• excess secretion (hyper secretion) or
• decreased target cell responsiveness
,
HYPOSECRETION
• Primary: due to defect in gland , less secretion
of hormone;
-Genetic
-Dietary deficiency (iodine)
-Toxic or chemical
-Autoimmune (thyroid)
-Diseases (carcinoma, tuberculosis)
-Iatrogenic(physician induced surgical removal)
-Idiopathic
HYPOSECRETION CONTD.
• Secondary:
Gland is normal but secreting less hormone
due to deficiency of it’s tropic hormone
• Treatment of hormone hypo secretion is to
replace the same hormone e.g. Insulin
injections
HYPERSECRETION
• By a particular gland may be:
• Primary ; defect in gland or
• Secondary; excessive stimulation from outside
Hyper secretion may be caused by;
1) Tumors
2)Immunological e.g .excessive stimulation of
thyroid by abnormal anti-body
3)Excessive use of steroids to build muscle mass
by athletes/body builders
• Treatment of hormonal hyper secretion;
-Surgical removal of tumor or destruction by
radiation
-Drugs which inhibit the synthesis or
secretion of hormone e.g. (anti-thyroid
drugs)
-Drugs inhibiting the action of hormones
ABNORMAL TARGET-CELL
RESPONSIVENESS
Endocrine dysfunction may be due to:
• non responsiveness of target cells , though
conc. of hormone in plasma may be normal
e.g.
-may be due to inborn lack of receptors for
hormone (testosterone) in testicular feminization
syndrome
or
-abnormal response may also occur due lack
of an enzyme essential for hormonal response
TARGET CELL RESPONSE
Can be varied by changing the number of
hormone-specific receptors (decreasing
the no. of receptors)i.e. down regulation
DOWN REGULATION:
The total no. of target cell receptors is reduced
e.g.
Sustained increase in insulin level
will gradually decrease the no. of receptors,
blunting the effect of insulin hyper secretion
HORMONAL INTERACTIONS
• The effects of hormone depends not only on
the conc. of hormone but also by the conc. of
other hormones.
• The effect of a hormone can be influenced by
the other hormone by 3 following ways;
1)Permissiveness
2)Synergism
3)Antagonism
PERMISSIVENESS
• One hormone must be present in adequate
amounts for the full effect of other hormone
• First hormone increases the target’s cell response
to other hormone (permissive action) e.g.
• Thyroid hormone increases the no. of receptors
in epinephrine target cells, thus increasing the
effectiveness of epinephrine.
• Cortisol also increases the effectiveness of
epinephrine.
SYNERGISM
• Occurs when actions of several hormones are
complementary (added) & their combined
effects is more than their individual effect. e.g.
• Synergistic action of follicle stimulating
hormone (FSH) and testosterone in sperm
production (spermatogenesis).
• This is due to influence on each other
receptors
ANTAGONISM
• Occurs when one hormone causes the loss of
other hormone’s receptors, thus decreasing the
effectiveness of other hormone. e.g.
• Progesterone which relaxes the uterus during
pregnancy inhibits the action of Estrogen (causing
contraction of uterus) during pregnancy by
causing loss of estrogen receptors of uterine
smooth muscles.
• Thus uterus is in a relaxed state, suitable for
developing fetus.
GOOD LUCK
&
WITH BEST WISHES