The Endocrine System

1. Chapter 18 The Endocrine System

2. Endocrine system Endo = inside crine = secrete hormon = to excite to get ~ 1# of endocrine tissue you would need to collect ALL the endocrine tissue from ~4-5 adults Exocrine cells secrete their product into a duct

3. Homeostasis Works in conjunction w/ nervous system slower to react/effects last longer endocrine glands include: pituitary, thyroid, parathyroid, adrenal, pineal, thymus, ORGANS - pancreas, gonads, hypothalamus (neuroendocrine organ), MINOR ORGANS - sm int., stomach, kidneys, heart, adipose cells

4. Paracrines locally acting chemicals that transfer information from cell to cell within single tissue These are not considered hormones since hormones are long-distance chemical signals

5. Hormone-target cell specificity A cell can only react to a H if it has a receptor on its plasma membrane or in its interior example: radio tuned to only pick up specific signals although there are many signals in the air concurrently

6. 3 factors effecting target cell activation 1. Blood levels of the H 2. # of receptors for that H on or in target cells 3. affinity (strength) of bond b/t H & receptor up-regulation - target cells form more receptors in response to decreased blood H levels down-regulation - prolonged exposure to high H [ ] desensitizes the target cell by losing receptors so they respond less vigorously to H stimulation

7. Mechanism of Hormone action Hormones have their effect by altering cell activity, not causing the activity alters plasma membrane permeability alters membrane potential thru open/closing ion channels (+) synthesis of proteins/enzymes w/in cell activates/deactivates enzymes induces secretory activity stimulates mitosis

8. Hormones Can be divided into 3 groups: amino acid derivatives peptide hormones lipid derivatives

9. Amino Acid Derivatives Small molecules structurally related to amino acids Synthesized from the amino acids tyrosine and tryptophan

10. Peptide Hormones Chains of amino acids Synthesized as prohormones: inactive molecules converted to active hormones before or after secretion

11. 2 Groups of Peptide Hormones Group 1: glycoproteins: more than 200 amino acids long, with carbohydrate side chains: TSH, LH, FSH Group 2: all hormones secreted by: hypothalamus hypophysis heart thymus digestive tract pancreas

12. 2 Classes of Lipid Derivatives Eicosanoids: derived from arachidonic acid Steroid hormones: derived from cholesterol

13. Eicosanoids act locally so are not always thought of as Hs b/c they are not circulating in the blood examples: leukotrienes - signaling chemicals that mediate inflammation & some allergic reactions prostaglandins - multiple functions including raising of BP, enhancement of uterine contractions, blood clotting, & inflammation

14. Steroid Hormones Are lipids structurally similar to cholesterol Released by: reproductive organs adrenal cortex (corticosteroids) kidneys (calcitriol) Remain in circulation longer than peptide hormones Are converted to soluble form, are absorbed gradually by liver, & may be excreted in bile or urine

15. Hormones circulate in the blood in two forms – free or bound Steroids and thyroid hormone are attached to plasma proteins and remain in circulation much longer All others are unencumbered and remain functional for less than one hour These are either absorbed & broken down by liver or kidneys, are broken down by enzymes, or diffuse out of the bloodstream to bind on target cells Hormone Concentrations in the Blood

16. Mechanism of Hormone action A hormone must bind to a receptor to exert its effect There are two ways in which this happens Second messenger mechanism Using intracellular receptor

17. Catecholamines and Peptide Hormones Are not lipid soluble so unable to penetrate cell membrane Bind to receptor proteins at outer surface of cell membrane (extracellular receptors) Uses intracellular intermediary (second messenger) to exert effects

18. cAMP as a second messenger

19. Intracellular Intermediaries First messenger: leads to second messenger may act as enzyme activator, inhibitor, or cofactor results in change in rates of metabolic reactions Important Second Messengers Cyclic-AMP (cAMP): derivative of ATP Cyclic-GMP (cGMP): derivative of GTP Calcium ions

20. Cascade Effect When the binding of a small number of hormone molecules to membrane receptors leads to thousands of second messengers in cell Magnifies effect of hormone on target cell

21. G Protein Enzyme complex coupled to membrane receptor Involved in link between first messenger and second messenger Binds GTP Activated when hormone binds to receptor at membrane surface Changes concentration of second messenger cyclic-AMP (cAMP) within cell Increased cAMP level accelerates metabolic activity within cell

22. Lower cAMP Levels Adenylate cyclase activity is inhibited Levels of cAMP decline cAMP breakdown accelerates & cAMP synthesis is prevented

23. Eicosanoids & Steroid Hormones Are lipid soluble Diffuse across membrane to bind to receptors in cytoplasm or nucleus, activating or inactivating specific genes Alter rate of DNA transcription in nucleus: change patterns of protein synthesis Directly affect metabolic activity and structure of target cell

24. Endocrine reflex Triggers NEGATIVE FEEDBACK SYSTEM humoral - PTH raises blood Ca, insulin, aldosterone neural - SNS to adrenals, oxytocin/ADH release from post. pituitary due to hypothalamic (+) hormonal - “tropic” Hs from Ant. Pit. As a result of the target gland raising H levels in blood

25. Hypothalamus - a neuroendocrine organ 1. Secretes regulatory hormones: Special hormones control endocrine cells in pituitary gland Contains autonomic centers: Exert direct neural control over endocrine cells of adrenal medullae

26. Pituitary gland aka Hypophysis Found in sella turcica pea sized & connected to hypothalamus via infundibulum secretes at least 9 Hs Master gland anterior (glandular) & posterior (neural)lobes

27. Neurohypophysis Derived from hypothalamic tissue Connected to the hypothalamus via the infundibulum Does not synthesize its own hormones Stores those made in the hypothalamus Oxytocin & ADH Formed from epithelial tissue originating from Rathke’s pouch (oral mucosa) No neural connection to hypothalamus Synthesizes its own hormones Communicates via a vascular connection Primary capillary plexus in hypothalamus Secondary capillary plexus in ant. pituitary

28. Hypophyseal secretory effectors

29. Activity of the Adenophypophysis The hypothalamus sends a chemical stimulus to the anterior pituitary Releasing hormones stimulate the synthesis and release of hormones Inhibiting hormones shut off the synthesis and release of hormones

30. Adenohypophyseal Hormones Tropic hormones 4 out of 6 are tropic (turn on/stimulatory) TSH, ACTH, FSH, LH All adenohypophyseal Hs affect their target cells via a second messenger system

31. Thyroid stimulating hormone TSH…thyrotropin Release triggered by thyrotropin-releasing hormone (TRH) Somatostatin is released by hypothalamus w/ increasing TSH levels to block release

32. Adrenocorticotropic hormone ACTH…corticotropin Release triggered by corticotropin-releasing hormone (CRH) (+) adrenal cortex to release corticosteroid Hs; specifically those that help the body resist stressors

33. Gonadotropins Follicle stimulating hormone (FSH) AKA follitropin Stimulates gamete production (sperm & egg) Luteinizing hormone (LH) AKA lutotropin Promotes production of gonadal hormones Stimulates maturation of the ovarian follicle and then triggers ovulation Stimulates interstitial cells of testes to produce testosterone…AKA interstitial cell stimulating hormone (ICSH) Virtually non-existant in prepubescents Release regulated by gonadotropin-releasing hormone (GnRH) & suppressed by rising levels of gonadal Hs

34. Prolactin (PRL) AKA mammotropin Some people consider it a gonadotropin but structurally similar to GH Well documented to (+) milk production in breasts May enhance testosterone production in males Release controlled by both prolactin-releasing hormone (PRH)…thought to be serotonin & prolactin-inhibiting hormone (PIH)…thought to be dopamine PIH dominates in males In women PRL levels rise & fall w/ estrogen levels (low estrogen…(+) PIH release/high estrogen…(+) PRH…when just prior to menstruation accounts for breast swelling & tenderness

35. Growth hormone (GH) AKA Somatotropin (STH) Major targets are bone & sk mm cells (+) most body cells to grow & divide Encourages protein synthesis & use of fat for fuel Secretion is regulated by 2 hypothalamic Hs Growth hormone-releasing hormone (GHRH) Growth hormone-inhibiting hormone (GHIH) Aka somatostatin (also (-) other ant.pit. Hs, GI, & pancreatic secretions—both endo & exocrine)

36. Melanocyte Stimulating Hormone Also called melanotropin (MSH) Stimulates melanocytes to produce melanin Inhibited by dopamine Secreted during: fetal development early childhood pregnancy certain diseases

37. Summary: The Hormones of the Pituitary Gland

38. Neurohypophyseal Hormones ADH & Oxytocin Both composed of 9 Aas & are almost identical Differ in only 2 of 9 AAs

39. Antidiuretic hormone (ADH) Inhibits or prevents urine formation Hypothalamus has osmoreceptors to monitor blood solute [ ] If too [ ] ADH is released which causes kidneys to resorb more water Other (+) include: pain, hypotension, nicotine, morphine (-) by alcohol & caffeine At high blood [ ] ADH has a vasoconstrictive effect…conditions such as severe blood loss cause ADH release which causes a rise in BP Aka Vasopressin

40. Diabetes insipidus Deficiency of ADH Leads to huge amounts of urine production Insipidus = tasteless…no glucosuria OK if thirst centers intact Dangerous in unconscious patients & w/head injury Head trauma victims must be carefully monitored

41. Oxytocin A strong stimulant of uterine contraction Amounts higher during childbirth & w/nursing Stretching of the uterus & cervix sends afferent signals to the hypothalamus…release of more oxytocin Triggers milk “letdown” or ejection in lactating breasts ) from PRL Both are positive feedback mechanisms

42. Oxytocin, cont. Natural & synthetic drugs (pitocin) are used to induce labor & speed it up Sometimes used to stop postpartum bleeding (compressing of ruptures blood vessels) May play role in sexual satisfaction & orgasm in males & non-lacting females May promote nurturing/affectionate behavior in non-sexual relationships…cuddling hormone

43. Thyroid gland Butterfly shaped w/2 lobes connected by an isthmus Made up of 2 types of cells Follicle cells (simple cuboidal or squamous epithelium) make up the follicle & produce a glycoprotein called thyroglobulin The lumen of the follicle contains thyroglobulin w/ attached Iodine molecules Thyroid hormone (TH) is produced from the iodinated thyroglobulin Parafollicular cells are interspersed b/t follicular epithelium & the CT separating the follicles Calcitonin is produced here

44. Thyroid Gland

45. Thyroid Hormone (TH) The body’s major metabolic hormone Actually 2 different Hs: T4 or thyroxin (major H secreted by follicle cells) T3 or triiodothyronine (most formed at target tissues by converting T4 to T3) Affects virtually every body cell except adult brain, spleen, testes, uterus, & the thyroid gland itself

46. TH, cont. Stimulates enzymes concerned w/glucose oxidation…increases BMR Increases body heat production (calorigenic effect) Increases # of adrenergic receptors in BVs so it is important in maintaining BP Regulator of tissue growth & development (esp skeletal, nervous, & reproductive system)also affects CV system, mm system, GI system, & hydration of skin

47. Synthesis of Thyroid Hormone

48. TH regulation Falling thyroxin blood levels trigger release of TSH…thyroxin TSH levels are usually lower during the day, peak just b/f sleep, & remain high during the night Conditions that increase the body’s energy requirements (pregnancy, prolonged cold) cause hypothalamus to release thyrotropin-releasing hormone (TRH)…TSH release from ant. pit. TRH overcomes the (-) feedback controls Somatostatin, rising levels of glucocorticoids & sex Hs (estrogens & testosterone), & excessively high blood iodide [ ] all (-) TSH release

49. Thyroid disorders Hypothyroid Myxedema – low BMR, feel cold, constipation, thick/dry skin, puffy eyes, edema, lethargy, mental sluggishness if it is a result of iodine insufficiency the thyroid gland enlarges to form a colloidal goiter (follicle cells produce colloid & store it but cannot iodinate it…TSH secretion increases…more colloid produced but no TH…after a while thyroid cells ‘burn out’ & gland atrophies) Cretinism – severe hypothyroid in infants; usually mentally retarded, short, disproportioned body, thick tongue; may be a genetic defect in thyroid or inadequate maternal dietary iodine intake Hyperthyroid Grave’s disease – believed to be autoimmune; increased BMR, sweating, rapid heart rate, nervousness, weight loss, exophthalmos (from edematous accumulation b/h eyes)

50. Exophthalmos

51. Calcitonin Produced by the parafollicular (C-clear) cells Antagonist to PTH by lowering blood calcium levels (+) Ca uptake & incorporation into bone matrix (-) osteoclast activity…bone resorption Excessive blood Ca levels (~20% above normal) (+) calcitonin release Declining blood Ca levels (-) release Seems more important in childhood w/rapidly growing bones & rapidly changing blood Ca levels In adults it is a weak hypocalcemic agent

52. Parathyroid glands Usually 4 BB sized glands found on the posterior aspect of the thyroid gland Secretion of PTH is by chief cells As many as 8 glands have already been found and some have even been found in other areas of the neck & thorax

53. Parathyroid hormone (PTH) AKA parathormone Single most important H controlling Ca balance in the blood (+) from falling blood Ca levels (-) from hypercalcemia PTH release (+) 3 target organs…

54. PTH, cont. PTH release (+) Osteoclasts – to digest bony matrix & release Ca & phosphates to the blood Kidneys – to enhance reabsorption of Ca (& excretion of phosphates) Intestine – increases absorption of Ca by intestinal mucosa cells… PTH causes conversion of vitamin D from the inactive form absorbed in the skin into its active form, calcitriol Vit D is needed to absorb Ca from ingested food

55. Adrenal glands AKA suprarenal glands Dual glands Adrenal medulla – nervous tissue (SNS) Adrenal cortex – glandular tissue derived from embryonic mesoderm; majority of gland All adrenal hormones help us cope with extreme (stressful) situations

56. Adrenal cortex Produce over 2 dozen steroid Hs called corticosteroids 3 distinct layers or zones of cells Zona glomerulosa – produce mineralocorticoids Balance of water & minerals in body Zona fasciculata – produce glucocorticoids Metabolism of body cells, gluconeogenesis, anti-inflammatory Zona reticularis – produce gonadocorticoids Insignificant in adults, female libido? All corticosteroids are produced by some degree in all 3 layers

57. Mineralocorticoids Aldosterone is the most potent (95% of total); (+) distal tubules in kidneys to reabsorb Na ions from the forming urine & return them to bloodstream (same result of Na reabsorption from perspiration, saliva, & gastric juices) Remember…where Na goes, water will follow (+) of aldosterone secretion: hyperkalemia, hyponatremia, decreasing blood volume & decreasing BP (-) of secretion is due to the reverse factors ACTH has little to no effect on aldosterone release

58. Glucocorticoids Cortisol is the most important; help keep blood glucose levels constant w/sporadic meal patterns, very active responding to stress, anti-inflammatory Secretion promoted by ACTH Any stress will cause override of (-) feedback that normally would reduce cortisol levels Cortisol also enhances epinephrine’s vasoconstrictive effects to increase BP…ensuring circulatory efficiency to help distribute nutrients

59. Glucocorticoids, cont. Excessive levels of cortisone: Depress cartilage & bone formation (-) inflammation by preventing vasodilation Depresses the immune system Promotes changes in cardiovascular, neural, & GI function Frequently are the drug of choice for chronic inflammatory diseases

60. Cortisone diseases Hypersecretion Cushing’s disease (syndrome) – most often results from overmedication; also adrenal cortex tumors or tumors of pituitary causing release of ACTH Hyperglycemia, loss of mm/bone protein, salt/water retention…”moon face”, “buffalo hump” from fat redistribution, easy bruising, poor wound healing…tx w/ discontinuing drugs or removal of tumor Hyposecretion Addison’s disease – usually deficits of both glucocorticoids (cortisone) & mineralocorticoids (aldosterone) Weight loss, drop of plasma glucose & Na levels, rise in K levels…dehydration, hypotension…tx w/corticosteroid replacement

61. Cushing Syndrome

62. Gonadocorticoids AKA sex hormones Most are androgens; testosterone is most important Minimal amounts of estrogen production Not much function in the adult…adrenal androgens seem to be related to the female sex drive (libido) May convert to estrogens after menopause when ovarian estrogens are no longer produced

63. Adrenal medulla Chromaffin cells are modified ganglionic sympathetic neurons that secrete the catecholamines Epinephrine Norepinephrine

64. Catecholamines SNS fibers w/ fight or flight Blood sugar levels rise, vasoconstriction, tachycardia, diversion of blood from nonessential organs to brain, heart, & skeletal mm Catecholamines released after SNS (+) prolong response; response is brief in relation to effects of adrenocortical Hs 80% of Hs released are epi, 20% are norepi Epi is more potent for (+) heart & metabolic activities Norepi is more potent for (+)vasoconstriction & BP Epi is often used clinically as a heart stimulant and a bronchioldilator during asthma attacks

65. Small gland hanging from the roof of the third ventricle of the brain Secretory product is melatonin Melatonin is involved with: Inhibits reproductive functions Protects against free radical formation Day/night cycles & physiological processes that show rhythmic variations (body temperature, sleep, appetite) Pineal Gland

66. A triangular gland, which has both exocrine and endocrine cells, located behind the stomach Acinar cells produce an enzyme-rich juice used for digestion (exocrine product) Pancreatic islets (islets of Langerhans) produce hormones (endocrine products) The islets contain four cell types: Alpha (?) cells that produce glucagon Beta (?) cells that produce insulin Delta ( ) cells that produce somatostatin F-cells secrete pancreatic polypeptide (PP) – (-) g. bladder Pancreas

67. Insulin Produced by beta cells (islets of Langerhans) Major effect is lowering of blood sugar; also affects protein & fat metabolism Insulin enhances membrane transport of glucose into body cells like mm & fat cells…not liver, brain, & kidney tissue--these have easy access to glucose regardless of insulin levels Main (+) is hyperglycemia Any hyperglycemic H can also (+) release: glucagon, epi, GH, thyroxine, or glucocorticoids—all are called into action as blood glucose levels drop

68. Glucagon Produced by alpha cells (islets of Langerhans) Major target is the liver Promotes glycogenolysis; gluconeogenesis from lactic acid, fats & AAs 1 molecule of glucagon can cause the release 100 million molecules of glucose in to the blood Secretion (+) by falling blood sugar levels Secretion (-) by rise in blood sugar & somatostatin

69. Diabetes mellitus (DM) Hyposecretion or inactivity of insulin 3 cardinal signs Polyuria – decreased blood volume & dehydration Polydipsia – thirst centers (+) from dehydration Polyphagia – b/c present glucose cannot be used & body starts breaking down fat & protein stores for energy metabolism

70. Gonads: Male Testes located in an extra-abdominal sac (scrotum) produce testosterone & Inhibin (sperm maturation) Testosterone: Initiates maturation of male reproductive organs Causes appearance of secondary sexual characteristics and sex drive Is necessary for sperm production Maintains sex organs in their functional state Paired ovaries in the abdominopelvic cavity produce estrogens and progesterone They are responsible for: Maturation of the reproductive organs Appearance of secondary sexual characteristics Breast development and cyclic changes in the uterine mucosa

71. Lobulated gland located deep to the sternum in the thorax Major hormonal product is thymosin This hormone is essential for the development of the T lymphocytes (T cells) of the immune system Thymus

72. Heart – produces atrial natriuretic peptide (ANP), which reduces blood pressure, blood volume, and blood sodium concentration Gastrointestinal tract – enteroendocrine cells release local-acting digestive hormones Placenta – releases hormones that influence the course of pregnancy Kidneys – secrete erythropoietin, which signals the production of red blood cells; & renin which is a powerful vasoconstrictor Skin – produces cholecalciferol, the precursor of vitamin D Adipose tissue – releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditure; resistin – reduces insulin sensitivity Other Hormone-Producing Structures

73. Four types of hormone interaction Permissiveness – one hormone cannot exert its effects without another hormone being present Synergism – more than one hormone produces the same effects on a target cell Antagonism – one or more hormones opposes the action of another hormone Integration – hormones produce different & complementary effects Interaction of Hormones at Target Cells

74. General Adaptation Syndrome (GAS) AKA stress response How bodies respond to stress-causing factors Divided into 3 phases: alarm phase resistance phase exhaustion phase

75. Alarm Phase Is an immediate response to stress directed by ANS Energy reserves mobilized (glucose) “Fight or flight” responses Dominant hormone is epinephrine

76. 7 Characteristics of Alarm Phase Increased mental alertness Increased energy consumption Mobilization of energy reserves (glycogen and lipids) Circulation changes: increased blood flow to skeletal muscles decreased blood flow to skin, kidneys, and digestive organs Drastic reduction in digestion and urine production Increased sweat gland secretion Increases in blood pressure, heart rate, and respiratory rate

77. Resistance Phase Entered if stress lasts longer than few hours Dominant hormones are glucocorticoids Energy demands remain high Glycogen reserves nearly exhausted after several hours of stress

78. Effects of Resistance Phase Mobilize remaining lipid and protein reserves Conserve glucose for neural tissues Elevate and stabilize blood glucose concentrations Conserve salts, water, and loss of K+, H+

79. Exhaustion Phase Begins when homeostatic regulation breaks down Failure of 1 or more organ systems will prove fatal Mineral imbalance

80. Interactions between Endocrine and Other Systems