IVMS Endocrine Secretion and Action II


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IVMS Endo-Endocrine Secretion and Action II

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IVMS Endocrine Secretion and Action II

  1. 1. ENDOCRINE SYSTEM BMS Part II Prepared and presented by: Marc Imhotep Cray, M.D. Drag/Drop Hormone Match ZeroBioSee: IVMS Endo-Endocrine Secretion and Action Part I
  2. 2. Target Cell Receptors at Three Locations Textbook in Medical Physiology And PathophysiologyEssentials and clinical problemshttp://www.zuniv.net/physiology/book/content.htm 2Section VII: Endocrine Glands
  3. 3. SIGNAL TRANSDUCTION See: G-protein Signal Transduction 3
  4. 4. EXAMPLE: subdivisions of the adrenal gland 4
  5. 5. Endocrine System Rapid Review See IVMS Endo-Endocrine Secretion and Action• Communication system – Allows for cells in distant parts of body to communicate – Communication generally slower in onset, but longer in duration, compared to nervous system communication• Consists of all the organs that secrete hormones (endocrine organs) 5
  6. 6. Hormones• Chemical Messengers• Produced by an endocrine gland• Released into and carried via bloodstream to target tissues – Target tissues = tissue bearing receptors that can bind and physiologically respond to the chemical messenger in question – Amount of chemical messenger produced and released into circulation is generally very small 6
  7. 7. Peptide Hormones• Majority of hormones are proteins/peptides• Preprohormones prohormones active• form• Bind to receptors located on the plasma membrane (surface receptors)• Responses generally occur very rapidly and are short-lived, compared to steroid hormone responses 7
  8. 8. Cell Surface Receptors1. G-protein coupled receptors2. Enzyme receptors3. Receptors associated with ion channels 8
  9. 9. G-Protein Coupled Receptors Animation: G-protein Signal Transduction at Texas A&M• Hormone binds to extracellular site on receptor• On cytoplasmic side, receptor is associated with inhibitory or stimulatory G-Proteins (guanine- binding)• Hormone binding on extracellular side activates intracellular G-proteins• Activated G-Proteins interacts with effector proteins (ion channels and enzymes) to elicit physiological response 9
  10. 10. G-Protein Coupled Receptors 10
  11. 11. Enzyme Receptors• Hormone binds to extracellular portion of receptor• Site on cytoplasmic portion of receptor has enzymatic activity that is activated by hormone binding on the extracellular side• Altered enzyme activity leads to chain of reactions that produce physiological response 11
  12. 12. Enzyme Receptors (animation) 12
  13. 13. Receptors Possessing Ion Channels• Hormone binds to site on extracellular part of receptor• Receptor itself also functions as ion channel• Binding of hormone to extracellular portion of the receptor causes change in shape of receptor that alters open/closed ion channel status 13
  14. 14. Receptors Possessing Ion Channels 14
  15. 15. Steroid Hormones• Modified Cholesterol Derivatives – Cholesterol = precursor for their production – Have fused ring structures• Are lipid soluble – Readily dissolve in and pass through plasma membrane – Bind to cytoplasmic or nuclear receptors• Alter gene transcription/protein production• Physiologic effects occur more slowly but last longer than peptide hormone responses 15
  16. 16. Steroid Hormone Production• Adrenal glands: aldosterone, cortisol, and androgens• Kidneys: 1,25-dihydroxyvitamin D3• Gonads – Ovaries: progesterone and estrogens – Testes: androgens (testosterone) See Animation: Biochemistry of Cholesterol by Rodney F. Boyer 16
  17. 17. Amine Hormones• Amino acid (tyrosine) derivatives• Includes: – T3 (triiodothyronine)and T4 (thyroxine) = thyroid hormones – Catecholamines • Epinephrine & norepinephrine = adrenal (medulla) hormones important in stress response • Dopamine (hypothalamic hormone)Animation: Adrenaline Action University of Washington 17
  18. 18. Neurons vs Endocrine Cells Neurons Endocrine Cells• Respond to environ- • Respond to environ- mental changes by mental changes by production and production of transmission of electrical hormones signals • Stimulate effector cells• stimulate effector cells via hormone release via NT release into the into the bloodstream synapse 18
  19. 19. Neuroendocrine Cells• Cells with properties of both neurons and endocrine cells• Specialized neurons that, when stimulated, produce chemical messengers (hormones) that are released into the circulatory system• Represent the site of functional overlap of the neural and endocrine system 19
  20. 20. Coitus-Induced Ovulation• Neuroendocrine Reflex• Occurs in rabbits, cats, ferrets, camel, llama• Ovulation is triggered by mating - does not occur in the absence of mating• Neural signals initiated by mating alter reproductive hormones to trigger ovulation 20
  21. 21. Prolactin and Oxytocin• Prolactin = hormone from the anterior pituitary that plays a role in milk formation• Oxytocin = hormone from the posterior pituitary that plays a role in milk release and uterine contraction 21
  22. 22. Milk Let-Down Reflex• Suckling of newborn produces neural signals that stimulate neurons in hypothalamus to secrete oxytocin• Oxytocin produces contraction of smooth muscle in the mammary glands the moves milk through ducts and expels it from the nipple, thus promotes milk release• Mental stimuli can also produce neural signals that cause same response – Lactating women can experience milk let-down in response to crying baby 22
  23. 23. Links to the individual hormones 23
  24. 24. Hypothalamic-Pituitary Axis• Hypothalamus – Region of brain (diencephalon) – Lies below third ventricle at base of brain – Important regulator of endocrine action• Pituitary Gland (hypophysis) – Endocrine gland connected to hypothalamus by infundibulum (stalk containing nerves and small blood vessels) 24
  25. 25. Animation :Thyroid Gland Functioning by Leif Saul 25
  26. 26. Hypothalamus • Contains neuroendocrine cells• Contains neuroendocrine whose cells that release – cell bodies lie within neurohormones which hypothalamus • Hypothalamus = site of hormone 1. enter the portal vessels production and are transported to – axons travel through anterior pituitary hypothalamic-pituitary stalk 2. regulate anterior and terminate in posterior pituitary hormone pituitary production • Posterior pituitary = site of hormone storage and release 26
  27. 27. Pituitary Gland• In humans has two lobes = distinct glands – Anterior (toward front of head) lobe = adenohypophysis – Posterior (toward back of head) lobe = neurohypophysis• Lobes connected to hypothalamus by different means – Anterior lobe connected by (portal) blood vessels – Posterior lobe connected by nerves (axons) 27
  28. 28. Textbook in Medical Physiology And PathophysiologyEssentials and clinical problemshttp://www.zuniv.net/physiology/book/content.htmSection VII: Endocrine Glands 28
  29. 29. Pituitary Gland 29
  30. 30. Posterior Pituitary• Outgrowth of the hypothalamus; composed of neural tissue• Specific neuroendocrine cells in hypothalamus have axons that project through the stalk and into the posterior pituitary• Secretes two important hormones – Oxytocin (OXY) – Antidiuretic hormone (ADH) 30
  31. 31. Oxytocin and ADH: Production and Release• Produced in cell bodies in hypothalamus• Stored in and released from axon terminals in the posterior pituitary• Both hormones are also produced in other brain areas and function in brain as neurotransmitters/neuromodulators 31
  32. 32. 32
  33. 33. OXY and ADH Action• Oxytocin – Acts on smooth muscle in the uterus and breast – Produces contractions that result in parturition and milk let-down• ADH – Acts in kidney to regulate water balance and control blood pressure 33
  35. 35. 35
  36. 36. Anterior Pituitary• Endocrine (hormone-secreting) gland containing several different cells types – Lactotrophs; secrete prolactin – Gonadotrophs; secrete LH and FSH – Somatotrophs; secrete Growth hormone – Thyrotrophs; secrete Thyroid stimulating hormone – Corticotrophs; secrete Adrenocorticotropic Hormone• Connected to hypothalamus by portal blood vessels 36
  37. 37. Hypothalamus Hypophysiotrophic HormonesInhibitory Hormones (Stimulatory ‘Releasing’ Hormones) Anterior Pituitary ACTH, GH, PRL, TSH, FSH, LH, Endocrine Gland 37
  38. 38. Hypothalamic Releasing Hormones• Produced in and released from hypothalamus• Enter portal blood vessels and are transported to ANTERIOR PITUITARY• Stimulate discrete cell types within anterior pituitary to secrete additional hormone(s) 38
  39. 39. Hypothalamic Releasing Hormones• Corticotropin Releasing Hormone (CRH) – Acts on corticotrophs – Stimulates AP production of adrenocorticotropic hormone (ACTH)• Thyrotropin Releasing Hormone (TRH) – Acts on thyrotrophs – Stimulates AP production of Thyroid Stimulating Hormone (TSH) 39
  40. 40. Hypothalamic ‘Releasing’ Hormones• Gonadotropin Releasing Hormone (GnRH) – Previously known as Luteinizing Hormone Releasing Hormone (LHRH) – Acts on lactotrophs to stimulate AP production of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) 40
  41. 41. Hypothalamic Releasing & Inhibitory Hormones• Growth Hormone Releasing Hormone (GHRH = somatotropin) – Acts on somatotrophs – Stimulates AP production of Growth Hormone (GH)• Growth Hormone Inhibitory Hormone (GIH = somatostatin) – Acts on somatotrophs – Inhibits AP production of Growth Hormone 41
  42. 42. Hypothalamic Dopamine Production/Release• Distinct dopamine-secreting neurons in hypothalamus• Dopamine enters portal vessels and is transported to Anterior Pituitary• Acts on lactotrophs to INHIBIT AP production of Prolactin 42
  43. 43. PRL vs Other AP Hormones• With the exception of PRL, other AP hormones are not secreted unless stimulated by ‘releasing’ hormones from hypothalamus• PRL is continuously produced/secreted unless inhibited by hypothalamic dopamine 43
  44. 44. HYPOTHALAMUS SUMMARY TRH GnRH DA OXY CRH GHRH/GHIH ADH + + + + - - TSH FSH/LH PRL OXY ADH ACTH GH + + + + Breast +Thyroid Ovary/Testes + Breast All Tissues + Adrenal Cortex 44
  45. 45. Thyroid Gland• Located in the neck; in front and on either side of trachea• Secretes two hormones – T3 = triiodothyronine – T4 = thyroxine Modified tyrosine• T4 secretion > T3 secretion molecules• T4 converted to T3 in most tissues, especially liver and kidney• T3 is more active hormone than T4 45
  46. 46. Thyroid Hormones• Require iodine for synthesis – Iodine absorbed in GI tract by active transport; converted to iodide in process – Iodide is taken up by thyroid gland, by active transport process, and converted back to iodine• Iodine is incorporated into T3 and T4 46
  47. 47. Thyroid Hormones• Stimulate growth and metabolism• Function in fetal/early postnatal brain development – Iodine deficiency that results in maternal or fetal thyroid hormone deficiency can result in severe mental retardation• Functions in adult brain function 47
  48. 48. Diseases of Thyroid Gland With eMedicine Article links:• Hypothyroidism = underactive thyroid – Slowed metabolic rate, fatigue, weight gain – Cretinism, if present and untreated at birth• Hyperthyroidism = overactive thyroid – Increased metabolic rate – Enlargement of thyroid gland (goiter) – Weight loss, nervousness, irritability – Intolerance to heat – Bulging eyeballs 48
  49. 49. Adrenal Glands With eMedicine Article links:• Paired glands; located on top of kidneys• Each adrenal gland has two parts – Medulla • Inner portion • Synthesizes/secretes epinephrine and norepinephrine (stress hormones) • Pheochromocytoma – Cortex • Outer portion • Secretes steroid hormones • Cushing Syndrome 49
  50. 50. Adrenal Cortex Steroid Hormones• Cortisol and Corticosterone – Regulate metabolism during fasting – Glucocorticoids• Aldosterone – Regulates Na+ and K+ balance; promotes Na+ reuptake in kidney – Mineralocorticoid – Hyperaldosteronism, Primary• Dehydroepiandrosterone – Androgen (testosterone precursor) 50
  51. 51. Diseases of Adrenal Glands With eMedicine article links:• Cushing’s Disease – hyperactive adrenal cortex – rounded face & obesity – Thin, frail skin poor wound healing – Hirtsuism (excess hair growth) in females• Addison’s Disease = adrenal cortex insufficiency – Decreased appetite, weight loss – Cold intolerance – Stress susceptibility 51
  52. 52. Parathyroid Glands• Located within thyroid gland• Secrete parathyroid hormone (PTH) – regulates plasma Ca++ and PO3++ levels – requires Vitamin D3 as cofactor• PTH excess bone demineralization• PTH insufficiency abnormal muscle contraction (tetany) eMedicine Articles: Hyperparathyroidism Hypoparathyroidism 52
  53. 53. Hormone Production Regulation1. Neural control – Hypothalamic releasing hormones2. Plasma Constituent – PTH; regulated by serum Ca++ levels – Insulin; regulated by serum glucose levels3. Hormonogen (hormone precursor) – Aldosterone; regulated by angiotensin levels 53
  54. 54. Hormone Production Regulation• Ingestion or biosynthesis of precursor• Hypothalamic-Pituitary Control 54
  55. 55. Plasma Constituent• PTH production by parathyroid glands• PTH regulates serum calcium and phosphate levels• PTH secretion is regulated by serum calcium levels – Increased serum calcium inhibitis PTH secretion – Decreased serum calcium stimulates PTH secretion 55
  56. 56. PTH Target Tissues• Bone – Increases bone resorption; moves calcium and phosphate from bones into extracellular fluid• Kidney – Stimulates activation of Vitamin D (converts 25(OH)vitamin D to 1,25-dihyrdoxyvitamin D – Increases tubular calcium reabsorption; decreases tubular phosphate reabsorption• Intestine – Activated Vit D increases intestinal absorption of calcium 56
  57. 57. PTH Regulation Intestine Kidney Bone + + + Serum Ca++Serum Ca++ + Parathyroid Glands 57
  58. 58. Hormonogen Regulation• Hormonogen = (inactive) hormone precursor participates in physiological response to environmental changes• Example: Aldosterone production by adrenal cortex• Hormone secreted into plasma acts on hormonogen and converts it to active hormone 58
  59. 59. Aldosterone• Steroid hormone from adrenal cortex• Regulates ion balance – Target tissue = collecting ducts in nephrons of kidney – Stimulates reabsorption of Na+ from ultrafiltrate back into bloodstream 59
  60. 60. Aldosterone Regulation• Angiotensinogen = hormonogen secreted into blood by liver• Angiotensinogen is converted to Angiotensin by Renin – Angiotensin = active form of hormone • Stimulates adrenal cortex to produce/release aldosterone – Renin = kidney hormone produced in response to drop in blood pressure or blood volume 60
  61. 61. + Kidney Liver Aldosterone Renin + AdrenalAngiotensinogen Angiotensin Cortex 61
  62. 62. Ingestion or Biosynthesis of Precursor• 1,25-dihydroxyvitamin D3 production – Vitamin D3 ingested in diet or synthesized in skin • in skin, ultraviolet radiation converts cholesterol derivative to Vit D3 • Subsequently modified by hydroxylations in liver and kidney – Main action of 1,25-dihydroxyvitamin D3 is to stimulate intestinal Ca++ absorption• Thyroid hormones – Tyrosine (amino acid) ingested or produced by interconversion of other amino acids – Modified by iodinations – T3 and T4 regulate metabolism and affect brain development/function 62
  63. 63. Hormone Production RegulationHypothalamic-Pituitary Control; negative feedback loops – Hormone produced by the terminal endocrine gland in an endocrine axis feeds back at the level of the hypothalamus and/or pituitary to ultimately inhibit its own production – Examples: • TH in thyroid • Cortisol in adrenal cortex 63
  64. 64. Endocrine System and Aging• Endocrine glands decrease in size with aging• Hormonal profile changes with aging – Generally hormone concentrations decrease with aging – Some hormone concentrations increase with aging • e.g. adrenal glucocorticoids (cortisol/corticosterone) which, in higher concentrations, over time, damage brain/neural tissues• Receptor numbers and/or receptor responsiveness are altered with aging• Collectively, these changes decrease organisms ability to respond to environmental changes and cope with stress 64
  65. 65. Anabolic Steroids• Synthetic testosterone• Clinically used to promote anabolic effects (growth) – Estrogen and Testosterone promote GH and IGF-I secretion that results in prepubertal growth spurt and induces closure of the bone growth plate at puberty – Testosterone (but not estrogen) has anabolic effect on protein synthesis that produces increased muscle mass• Abused by athletes in an attempt to gain muscle mass and increased strength 65
  66. 66. Negative Side Effects of Anabolic Steroids In men In women– Decreased plasma – Virilization testosterone • deepened voice– Sterility • hirsutism– Testicular atrophy – Alopecia (hair loss)– Gynecomastia – Acne Both sexes –Hypertension and cardiovascular disease –Liver tumors –AIDS (via sharing needles for injection) 66
  67. 67. End of SessionServices provided by Imhotep Virtual Medical SchoolIndividualized Webcam facilitated USMLE Step 1 Tutorials with Dr. Cray Starting at$50.00/hr., depending on pre-assessment. 1 BMS Unit is 4 hr. General Principles and someOrgan System require multiple units to complete in preparation for the USMLE Step 1A HIGH YIELD FOCUS in Biochemistry / Cell Biology, Microbiology / Immunology, the 4 P’s-Physiology, Pathophys., Path and Pharm and Intro to Clinical MedicineWebcam Facilitated USMLE Step 2 Clinical Knowledge and Clinical Skills didactic tutorialsstarting at $75.00 per hour /1 Unit is 4 hours, individualized one-on-one and group sessions,Including Introduction to Clinical Medicine and all Internal Medicine sub-specialities at theclerkship level. For questions or more information.. drcray@imhotepvirtualmedsch.comALL e-books and learning tools provided 67