ENDOCRINE SYSTEM

OVERVIEWBY

DR. SYED AFTAB OMAR (MBBS, MD)

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 moleculesUse 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 cellsAutocrine HoromnesSite of synthesis & effector (target) same cellRecurrent / 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 & Polypeptides2. Steroids3. Amino Acid tyrosine derivativeProteins & Polypeptides< 100 amino acids – peptide> 100 amino acids – proteinExamples:• Ant. & Post. Pituitary hormones• Insulin / Glucagon• Growth hormone• Parathyroid hormone etc.

Steroids: Are derived from cholesterolhave Cyclopentanoperhydrophenan-threne nucleusExample:• 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

C-Peptide

A-chain

B-chain

SS

SS

S S

SS

SS

SS

Connecting peptide

Insulin

HOOC

NH2

NH2

NH2

COOH

COOH

Proinsulin

A-chainB-chain

1

5

1015 20

25

30

1 5 10 15

20

1 5 10 15 20 25 30

1

5 1015

20

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 ofPeptide 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 HORMONESReleasing 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 – except1. THYROXINE –by combining with TYHYROGLOBULIN2. INSULIN – can be stored in β – cells of pancreas in complex form with Zinc3. 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 backi. Hormone – Hormone levelii. Substrate – Hormone leveliii.Mineral – Hormone level

(B) Neural Control i. Adrenergicii. Cholinergiciii.Dopaminergiciv.Serotinergicv. GABAergic

(C) Chronotropic Controli. Diurnal Rhythmii. Sleep – Wake Rhythmiii.Menstrual Rhythmiv.Seasonal Rhythmv. Developmental Rhythmvi.Circhoral Rhythmvii.Ultradian Rythm

(C) Chronotropic Control1. Diurnal Rhythm- ↑ Prolactin secretion during night2. Sleep Wake Rhythm- Infants / Children – ↑ GH during sleep- ↑ ACTH & ↑ Cortisol during sleep3. Menstrual Rhythm- reproductive life (15 – 45 yrs)♀- Ovarian steroids – Estrogen & Progesterone4. Seasonal Rhythm- Esp. in lower animals (Frogs – Hibernate)5. Developmental Rhythm- eg., Growth Rythm6. Circhorral Rhythm- change on hourly basis eg., insulin after food intake7. 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 tissuesii. Binding with tissuesiii. Excretion by LIVER into BILE- By conjugation with glucoronide etc.iv. Excretion by kidneys into urinev. 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.

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