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Endocrinology

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Endocrinology

  1. 1. The EndocrineThe Endocrine SystemSystem
  2. 2. Endocrine History Claude Bernard (mid 1800s) pancreas, liver brain, smooth ms. internal environ A.A. Berthold (1849) reproductive hormones and behavior
  3. 3. Endocrine History Charles Brown-Sequard (1889) Harvard 1864-1868 M.D. in NY 1873-1878 bull testis extracts
  4. 4. Important Physiologists Walter Cannon homeostasis sympathetic nervous system Bodily Changes in Hunger, Fear, and Rage
  5. 5. Overview of the Endocrine System  System of ductless glands that secrete hormones  Hormones are “messenger molecules”  Circulate in the blood  Act on distant target cells  Target cells respond to the hormones for which they have receptors  The effects are dependent on the programmed response of the target cells  Hormones are just molecular triggers
  6. 6. Hormone Types: •peptide or protein = at least 3 amino acids • peptides (short chains of amino acids), and proteins (long chains of amino acids) •steroid = derived from cholesterol •amine = derived from single amino acids (tryptophan, tyrosine)
  7. 7. 7 Endocrine Organs  Purely endocrine organs  Pituitary gland  Pineal gland  Thyroid gland  Parathyroid glands  Adrenal: 2 glands  Cortex  Medulla  Endocrine cells in other organs  Pancreas  Thymus  Gonads  Hypothalamus
  8. 8. Mechanisms of hormone release (a) Humoral: in response to changing levels of ions or nutrients in the blood (b) Neural: stimulation by nerves (c) Hormonal: stimulation received from other hormones
  9. 9. Control of Endocrine Function A. Positive B. or Negative Feedback mechanisms Self-regulating system
  10. 10. STIMULUS Hypothalamus Releasing Hormone (Release-Inhibiting Hormone) Pituitary Stimulating Hormone Gland Hormone Target
  11. 11. Positive Feedback • Not common • Classic example: • Action of OXYTOCIN on uterine muscle during birth.
  12. 12. Positive Feedback • Baby pushes on cervix • Nervous signal to Hypothalamus • Hypothal. manufactures OXY • OXY transported to POSTERIOR PITUITARY & released • OXY stimulates uterine contraction • Loop stops when baby leaves birth canal
  13. 13. Negative Feedback • Most common control mechanism • Level of hormone in blood or body’s return to homeostasis shuts off loop at hypothalamus and pituitary
  14. 14. Negative Feedback: Thyroid
  15. 15. Basic Structure of Feedback Loop • Environmental Stimulus • Stimulates Control Center (Brain-hypothal.) • Hypothalamic hormones stim. Pituitary • Pituitary hormone stim. Target area • Target area produces change • Change acts negatively or positively on the cycle.
  16. 16. 16 Hypothalamic Hormomes • Release Inhibiting Hormones • Somatostatin • Prolactin release inhibiting hormone-PIH • Releasing Hormones • Thyrotropin releasing hormone-TRH • Growth hormone releasing hormone- GHRH
  17. 17. 17 Number of Receptors • Down-regulation: is the decrease of hormone receptors which decreases the sensitivity to that hormone • Up-regulation: is the increase in the number of receptors which causes the cell to be more sensitive to a particular hormone
  18. 18. Pituitary__________ (hypophysis) Hypothalamus___________ Hypothalamus__ Anterior pituitary__ (adenohypophysis) _____________Posterior pituitary (neurohypophysis) Learn the 3 endocrine organs on this slide: Hypothalamus Pituitary (hyophysis) Pineal
  19. 19. Hypothalamus (general) Connection to pituitary Neuronal to POSTERIOR PITUITARY Endocrine to ANTERIOR PITUITARY RH = Pituitary releasing hormones RIH = Pituitary release inhibiting hormones
  20. 20. Two divisions:  Anterior pituitary (adenohypophysis)  Posterior pituitary (neurohypophysis) Sits in hypophyseal fossa: depression in sella turcica of sphenoid bone Pituitary secretes 9 hormones The Pituitary 1. TSH 2. ACTH 3. FSH 4. LH 5. GH 6. PRL 7. MSH 8. ADH (antidiuretic hormone), or vasopressin 9. Oxytocin _________________________________________________________________ The first four are “tropic” hormones, they regulate the function of other hormones ________
  21. 21. What the letters stand for…  TSH: thyroid-stimulating hormone  ACTH: adrenocorticotropic hormone  FSH: follicle-stimulating hormone  LH: luteinizing hormone  GH: growth hormone  PRL: prolactin  MSH: melanocyte-stimulating hormone  ADH: antidiuretic hormone  Oxytocin
  22. 22. Hypothalamus controls anterior pituitary hormone release  Releasing hormones (releasing factors) Secreted like neurotransmitters from neuronal axons into capillaries and veins to anterior pituitary (adenohypophysis) TRH-----turns on TSH CRH-----turns on ACTH GnRH (=LHRH)---turns on FSH and LH PRF-----turns on PRL GHRH----turns on GH  Inhibiting hormones PIF-----turns off PRL GH inhibiting hormone ---turns off GH
  23. 23. What the letters mean…  Releasing hormones (releasing factors) of hypothalamus TRH (thyroid releasing hormone) -----turns on* TSH CRH (corticotropin releasing hormone) -----turns on ACTH GnRH (gonadotropin releasing hormone) ---turns on FSH and LH PRF (prolactin releasing hormone) -----turns on PRL GHRH (growth hormone releasing hormone) ----turns on GH  Inhibiting hormones of hypothalmus PIF (prolactin inhibiting factor) -----turns off PRL GH (growth hormone) inhibiting hormone ---turns off GH
  24. 24. So what do the pituitary hormones do?  TSH stimulates the thyroid to produce thyroid hormone  ACTH stimulates the adrenal cortex to produce corticosteroids: aldosterone and cortisol  FSH stimulates follicle growth and ovarian estrogen production; stimulates sperm production and androgen-binding protein  LH has a role in ovulation and the growth of the corpus luteum; stimulates androgen secretion by interstitial cells in testes The four tropic ones regulate the function of other hormones:
  25. 25. The others from the anterior pituitary…  GH (aka somatrotropic hormone) stimulates growth of skeletal epiphyseal plates and body to synthesize protein  PRL stimulates mammary glands in breast to make milk  MSH stimulates melanocytes; may increase mental alertness
  26. 26. 26 From the posterior pituitary (neurohypophysis) structurally part of the brain  ADH (antidiuretic hormone AKA vasopressin) stimulates the kidneys to reclaim more water from the urine, raises blood pressure  Oxytocin prompts contraction of smooth muscle in reproductive tracts, in females initiating labor and ejection of milk from breasts
  27. 27. Anterior Pituitary Hormones HORMONE TARGET FUNCTION Thyroid (TSH) Stimulating Thyroid gland TH synthesis & release Growth (GH) Many tissues growth Adrenocortico- Tropin (ACTH) Adrenal cortex Cortisol release (androgens) Prolactin (Prl) Breast Milk production Follicle (FSH) Gonads Egg/sperm prod. Luteinizing (LH) Gonads Sex hormones
  28. 28. 28 Pituitary__________ (hypophysis) Hypothalamus___________ Now try and remember the anatomy
  29. 29. 29 The Thyroid Gland  Anterior neck on trachea just inferior to larynx  Two lateral lobes and an isthmus  Produces two hormones  Thyroid hormone: tyrosine based with 3 or 4 iodine molecules  T4 (thyroxine) and T3  Calcitonin involved with calcium and phosphorus metabolism
  30. 30. 30  Thyroid is composed of spherical follicles  Follicle cells: produce thyroglobulin, the precursor of thryoid hormone (thyroxin)  Colloid lumen is of thyroglobulin  Parafollicular “C” cells: produce calcitonin
  31. 31. Transportation of T.hormones  Thyroxine binding globuline  Thyroxine binding prealbumine  Albumine (one tenth) 31
  32. 32. 32 Some Effects of Thyroid Hormone (Thyroxine)  Increases the basal metabolic rate  The rate at which the body uses oxygen to transform nutrients (carbohydrates, fats and proteins) into energy  Affects many target cells throughout the body; some effects are  Protein synthesis  Bone growth  Decrease blood ca+ levels  Neuronal maturation  Cell differentiation
  33. 33.  Increases RBC production  Promotes growth  Increases heart rate  Increases rate and force of respiration  Increases the appetite  Increases secretion of digestive hormones  Essential for normal sexual function  Increases the demand of other hormones 33
  34. 34. Regulation Increases  Low basal metabolic rate  Leptin  Alfa melanocyte stimulating hormone Decreases  Excessive iodide intake  Stress  Somatostatin  Glucocorticoids  Dopamine 34
  35. 35. 35 The Effects of Calcitonin  Secreted from thyroid parafollicular (C) cells when blood calcium levels are high  Calcitonin lowers Ca++ by slowing the calcium-releasing activity of osteoclasts in bone and increasing calcium secretion by the kidney  Acts mostly during childhood
  36. 36. 36 The Parathyroid Glands  Most people have four  On posterior surface of thyroid gland (sometimes embedded)
  37. 37. 37 Parathyroids (two types of cells)  Rare chief cells  Abundant oxyphil cells (unknown function)  Chief cells produce PTH  Parathyroid hormone, or parathormone  A small protein hormone
  38. 38. 38 Function of PTH (parathyroid hormone or “parathormone”)  Increases blood Ca++ (calcium) concentration when it gets too low  Mechanism of raising blood calcium 1. Stimulates osteoclasts to release more Ca++ from bone 2. Decreases secretion of Ca++ by kidney 3. Activates Vitamin D, which stimulates the uptake of Ca++ from the intestine  Has opposite effect on calcium as calcitonin (which lowers Ca++ levels)
  39. 39. Regulation  Increase in blood ca+ levels decreases PTH secretion  Excessive ca+ in diet  Increases vit D synthesis  Increases reabsorption of ca+ from bones 39
  40. 40. Importance of ca+  Bone and teeth formation  Neuronal activity  Skeletal muscle activity  Cardiac activity  Smooth muscle activity  Secretary activity of glands  Cell division and growth  Coagulation of blood 40
  41. 41. 41 Adrenal (suprarenal) glands (“suprarenal” means on top of the kidney)  Each is really two endocrine glands  Adrenal cortex (outer)  Adrenal medulla (inner)  Unrelated chemicals but all help with extreme situations
  42. 42. 42 Adrenal Gland  Adrenal cortex  Secretes lipid-based steroid hormones, called “corticosteroids” – “cortico” as in “cortex”  MINERALOCORTICOIDS – Aldosterone is the main one  GLUCOCORTICOIDS – Cortisol (hydrocortisone) is the main one  Sex hormones  Adrenal medulla  Secretes epinephrine, norepinephrine and dopamine
  43. 43. Transport  Mineralocorticoids-globuline  Glucocorticoids-Glucocorticoids binding globuline  Around 6% flows freely in plasma  Sex hormones-Sex hormones binding globuline 43
  44. 44. Fate of corticosteroids  Degraded in liver  25% 0f corticosteroids are excreted in bile and feces  Remaining 75% in urin 44
  45. 45. Mineralocorticoids  Act on minerals particularly sodium and potassium  Those are  Aldosteron  11-deoxycorticosterone  Secreted from zona glomerulosa  Half life – 20mins  Life saving hormone 45
  46. 46. 46 Aldosterone, the main mineralocorticoid  Secreted by adrenal cortex in response to a decline in either blood volume or blood pressure (e.g. severe hemorrhage)  Is terminal hormone in renin-angiotensin mechanism  Prompts distal and collecting tubules in kidney to reabsorb more sodium  Water passively follows  Blood volume thus increases
  47. 47. Function  Increases reabsorption of sodium (renal tebules & sweat gland)  Increases in ECF volume  Increases potassium excreation 47
  48. 48. Regulation  Increase potassium conc. In ECF  Decrease sodium conc. In ECF  Decreases in ECF volume  Adrenocorticotropic hormone 48
  49. 49. Glucocorticoids  Mainly work on glucose metabolism  Secreted from zona faciculata  Three of them  Cortisol  Corticosterone  cortisone 49
  50. 50. 50 Cortisol, the most important glucocorticoid (Glucocorticoid receptors are found in the cells of most vertebrate tissues)  It is essential for life (life protecting hormone)  Helps the body deal with stressful situations within minutes  Physical: trauma, surgery, exercise  Psychological: anxiety, depression, crowding  Physiological: fasting, hypoglycemia, fever, infection  Regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions including water balance
  51. 51. Cont…  Mobilization of fatty acid from adipose tissue  Increases the utilization of fat as energy  Blood ca++ levels decreases  Stimulates osteoclastic activity  Causes destruction of eosinophils in reticuloendothelial cells  Increases the RBCs,platelats,neotrophils 51
  52. 52. Cont…  Needed for normal functioning of CNS  Increases the resistance to stress  It has a anti-inflamatory effect  Prevents the various reaction in allargic condition  Causes decrease in number of circulating T lymphocytes 52
  53. 53. 53 Cortisol, continued  Keeps blood glucose levels high enough to support brain’s activity  Forces other body cells to switch to fats and amino acids as energy sources  Catabolic: break down protein  Redirects circulating lymphocytes to lymphoid and peripheral tissues where pathogens usually are  In large quantities, depresses immune and inflammatory response  Used therapeutically  Responsible for some of its side effects
  54. 54. 54 Hormonal stimulation of glucocorticoids HPA axis (hypothalamic/pituitary/adrenal axis)  With stress, limbic system is stimulated , and sends impulses to hypothalamus  Hypothalamus sends CRH to anterior pituitary (adenohypophysis)  Through hypothalamo-hypophysis portal circulation  Pituitary secretes ACTH  ACTH goes to adrenal cortex where stimulates glucocorticoid secretion  Sympathetic nervous system can also stimulate it
  55. 55. 55  Steroid-secreting cells have abundant smooth ER  As opposed to rough ER in protein-secreting cells  Steroids directly diffuse across plasma membrane  Abundant lipid droplets  Raw material from which steroids made In general:
  56. 56. Sex hormones  Secreted from Zona Reticularis  Androgens (male sex hormones)  Dehydroepiandrosterone (most activated)  Androsterone  Testosterone  Small quantity of estrogen and progesterone also secreted by it 56
  57. 57. 57 Adrenal medulla  Part of autonomic nervous system  Spherical chromaffin cells are modified postganglionic sympathetic neurons  Secrete epinephrine and norepinephrine  Amine hormones  Fight/flight  Vesicles store the hormones
  58. 58. Adrenaline & Noradrenaline  Two types of receptor  Alpha adrenargic hormone  Beta adrenargic hormone  Increases oxygen consumption  Increases BMR  Increases blood glucose levels  Mobilizes the free fatty acid from adipose tissue  Decreases the blood coagulation time 58
  59. 59. Cont…  Increases heart rate  Increases force of contraction of the heart  Increases conductivity of cardiac muscle  Causes vasoconstriction  Increases systolic blood pressure  Increases  rate and force of respiration  Increases sweating 59
  60. 60. Cont…  Increases glycogenolysis  Causes vasodilatation in skeletal muscle  Enhances cortical arousal  Increases salivary secretion  Increases ACTH secretion  Decreases latency of nerve cells  Increases renin secrection 60
  61. 61. Dopamine  Secrated by adrenal medula  Also secretion by dopaminargic neurons of basal ganglia  Almost same action as noradrenaline 61
  62. 62. 62 The Pancreas Exocrine and endocrine cells  Acinar cells (forming most of the pancreas)  Head and body  Exocrine function  Secrete digestive enzymes  Islet cells (of Langerhans)  Tail of the pancreas  Endocrine function
  63. 63. 63 Pancreatic islet endocrine cells Alpha cells: secrete glucagon raises blood sugar mostly in periphery Beta cells: secrete insulin lowers blood sugar central part (are more abundant) Also rare Delta cells:secrete somatostatin inhibits glucagon/insuline
  64. 64. Insuline  Antidiabetic hormone  Increases transport and uptake of glucose  Promote peripheral utilization of glucose  Promote glycogenesis  Inhibits glycogenolysis  Increases the permeability for the amino acids of the cell membrane 64
  65. 65. Regulation  When blood sugar levels goes up  Excess amino acid in blood  By secretion of gastric hormones like gastrin,secratin,cholecystokinin  Parasympathetic stimulation to pancrease 65
  66. 66. Glucagon  Increases glycogenolysis in liver  Increases blood sugar levels  Inhibits secretion of gastric juices  Increases secretion of bile 66
  67. 67. Regulation Increases  Exercise  stress  Gastrin  Cortisol  cholicystokinin decreases  Somatostatin  Insuline  Free fatty acid  ketones 67
  68. 68. 68 The Gonads (testes and ovaries) main source of the steroid sex hormones  Testes  Interstitial cells secrete androgens  Primary androgen is testosterone  Maintains secondary sex characteristics  Helps promote sperm formation  Ovaries  Androgens secreted by thecal folliculi  Directly converted to estrogens by follicular granulosa cells  Granulosa cells also produce progesterone  Corpus luteum also secretes estrogen and progesterone
  69. 69. 69 The Pineal Gland  At the end of a short stalk on the roof of the diencephalon  Pinealocytes with dense calcium particles  Can be seen on x-ray (because of Ca++)  Melatonin helps regulate the circadium rhythm  The biological clock  Complicated feedback via retina’s visual input
  70. 70. 70 Endocrine cells in various organs  The heart: atrial natriuretic peptide (ANP)  Stimulates kidney to secrete more salt  Thereby decreases excess blood volume, high BP and high blood sodium concentration  GI tract & derivatives: Diffuse neuroendocrine system (DNES)
  71. 71. 71 Endocrine cells in various organs continued  The placenta secretes steroid and protein hormones  Estrogens, progesterone  CRH  HCG  The kidneys  Juxtaglomerular cells secrete renin  Renin indirectly signals adrenal cortex to secrete aldosterone  Erythropoietin: signals bone marrow to increase RBC production  The skin  Modified cholesterol with uv exposure becomes Vitamin D precursor  Vitamin D necessary for calcium metabolism: signals intestine to absorb CA++
  72. 72. Thank you… 72

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