ENDOCRINE SYSTEM

2. ENDOCRINE SYSTEM OVERVIEW BY DR. SYED AFTAB OMAR (MBBS, MD)

3. 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)

5. 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

6. 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

7. 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

8. Exocrine Glands- Pour secretion through duct system Dual Glands- Endocrine/ Exocrine functions – both are present e.g., Pancreas

9. 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

10. 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

11. ParacrineHoromones • Site of synthesis & site of action close together• Act on adjacent cells AutocrineHoromnes Site of synthesis & effector (target) same cell Recurrent / Periodic Glands • Appear & disappear according to physiological demand• e.g., Corpus Luteum & Placenta

13. 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

14. 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

15. CLASSIFICATION OF HORMONES Classification of Hormones: 1. Proteins & Polypeptides2. Steroids3. Amino Acid tyrosine derivative Proteins & Polypeptides < 100 amino acids – peptide> 100 amino acids – proteinExamples: • Ant. & Post. Pituitary hormones• Insulin / Glucagon• Growth hormone• Parathyroid hormone etc.

16. Steroids: Are derived from cholesterol have Cyclopentanoperhydrophenan- threne nucleus Example: • Cortisol• Aldosterone• Testosterone• Estrogen etc. Amino Acid – tyrosine Derivatives • Thyroid Hormones• Epinephrine / Norepinephrine

17. 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

18. 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

19. 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

20. Processing of Proinsulin Connecting peptide HOOC NH2 20 1 S S 1 15 5 A-chain 10 S B-chain 30 S S S 5 25 Proinsulin 10 20 15 C-Peptide S S 20 COOH NH2 1 5 10 15 S Insulin S A-chain S S COOH NH2 30 10 15 20 25 1 5 B-chain

21. 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

22. Synthesis & Secretion of Peptide Hormones

23. 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

24. 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.

25. 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 TYHYROGLOBULIN2. INSULIN – can be stored in β – cells of pancreas in complex form with Zinc3. ADH – by combining with; - Neurophysin – I - Neurophysin – II

26. 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

27. - 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

29. 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

30. 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

31. 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

32. 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

33. NEGATIVE FEED BACK CONTROL

38. HORMONAL REGULATION CONTD. Modes of Hormonal Regulation (A) Feed back system(B) Neural Control(C) Chronotropic Control

40. (A) Feed back system (Mainly)- Negative Feed back - Positive Feed backi. Hormone – Hormone levelii. Substrate – Hormone leveliii.Mineral – Hormone level

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

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

43. (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 & 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

44. 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

45. 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

46. Circadian Rhythm of Cortisol

47. 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

49. 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

50. OVER ALL FUNCTIONS CONTD. • Regulating RBC production (erythropoiesis) • Along with autonomic nervous system(ANS) regulate and integrate activities of CVS and digestive system