1. PowerPoint ® Lecture Slides prepared by Janice Meeking, Mount Royal College C H A P T E R Copyright © 2010 Pearson Education, Inc. 16 The Endocrine System: Part A

2. Copyright © 2010 Pearson Education, Inc. Endocrine System: Overview Acts with the nervous system to coordinate and integrate the activity of body cells Influences metabolic activities by means of hormones transported in the blood Responses occur more slowly but tend to last longer than those of the nervous system Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands

3. Copyright 2009, John Wiley & Sons, Inc. Nervous and Endocrine Systems Act together to coordinate functions of all body systems Nervous system  Nerve impulses/ Neurotransmitters  Faster responses, briefer effects, acts on specific target Endocrine system  Hormone – mediator molecule released in 1 part of the body but regulates activity of cells in other parts  Slower responses, effects last longer, broader influence

4. Copyright © 2010 Pearson Education, Inc. Endocrine System: Overview Some organs produce both hormones and exocrine products (e.g., pancreas and gonads) The hypothalamus has both neural and endocrine functions Other tissues and organs that produce hormones include adipose cells, thymus, cells in the walls of the small intestine, stomach, kidneys, and heart

5. Copyright © 2010 Pearson Education, Inc. Figure 16.1 Pineal gland Hypothalamus Pituitary gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Thyroid gland Adrenal glands Pancreas Ovary (female) Testis (male)

6. Copyright © 2010 Pearson Education, Inc. Chemical Messengers Hormones: long-distance chemical signals that travel in the blood or lymph Autocrines: chemicals that exert effects on the same cells that secrete them Paracrines: locally acting chemicals that affect cells other than those that secrete them Autocrines and paracrines are local chemical messengers and will not be considered part of the endocrine system

7. Eicosanoids Two families  prostaglandins  leukotrienes found in all body cells except red blood cells act as local hormones (paracrine and/or autocrine) in response to mechanical and chemical stimuli synthesized by clipping 20 carbon arachidonic acid from membrane phospholipids

8. Eicosanoids thromboxane is modified PG that constricts blood vessels and activates platelets rapid, short acting bind receptors on target cells stimulate or inhibit second messenger LTs stimulate chemotaxis and mediate inflammation

9. Eicosanoids PGs alter:  smooth muscle contraction  glandular secretion  blood flow  reproductive processes  platelet function  respiration  nerve impulses  lipid metabolism  immune response

10. Eicosanoids PGs promote:  inflammation  fever  pain intensity

11. Copyright © 2010 Pearson Education, Inc. Chemistry of Hormones Two main classes 1.Amino acid-based hormones Amines, thyroxine, peptides, and proteins NO Prostaglandins 2.Steroids Synthesized from cholesterol Gonadal and adrenocortical hormones

12. Copyright © 2010 Pearson Education, Inc. Mechanisms of Hormone Action Hormone action on target cells 1.Alter plasma membrane permeability of membrane potential by opening or closing ion channels 2.Stimulate synthesis of proteins or regulatory molecules 3.Activate or deactivate enzyme systems 4.Induce secretory activity 5.Stimulate mitosis

13. Copyright © 2010 Pearson Education, Inc. Mechanisms of Hormone Action Two mechanisms, depending on their chemical nature 1.Water-soluble hormones (all amino acid–based hormones except thyroid hormone) Cannot enter the target cells Act on plasma membrane receptors Coupled by G proteins to intracellular second messengers that mediate the target cell’s response

14. Copyright © 2010 Pearson Education, Inc. Mechanisms of Hormone Action 2.Lipid-soluble hormones (steroid and thyroid hormones) Act on intracellular receptors that directly activate genes

15. Copyright © 2010 Pearson Education, Inc. Plasma Membrane Receptors and Second- Messenger Systems cAMP signaling mechanism 1.Hormone (first messenger) binds to receptor 2.Receptor activates G protein 3.G protein activates adenylate cyclase 4.Adenylate cyclase converts ATP to cAMP (second messenger) 5.cAMP activates protein kinases

16. Copyright © 2010 Pearson Education, Inc. Plasma Membrane Receptors and Second- Messenger Systems cAMP signaling mechanism Activated kinases phosphorylate various proteins, activating some and inactivating others cAMP is rapidly degraded by the enzyme phosphodiesterase Intracellular enzymatic cascades have a huge amplification effect

17. Copyright © 2010 Pearson Education, Inc. Figure 16.2 Hormone (1st messenger) binds receptor. Receptor activates G protein (G S ). G protein activates adenylate cyclase. cAMP acti- vates protein kinases. Adenylate cyclase converts ATP to cAMP (2nd messenger). Receptor G protein (G S ) Adenylate cyclase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Hormones that act via cAMP mechanisms: Epinephrine ACTH FSH LH Inactive protein kinase Extracellular fluid Cytoplasm Active protein kinase GDP Glucagon PTH TSH Calcitonin 1 234 5

18. Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 1 Hormone (1st messenger) binds receptor. Receptor Hormones that act via cAMP mechanisms: Epinephrine ACTH FSH LH Extracellular fluid Cytoplasm Glucagon PTH TSH Calcitonin 1

19. Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 2 Hormone (1st messenger) binds receptor. Receptor activates G protein (G S ). Receptor G protein (G S ) Hormones that act via cAMP mechanisms: Epinephrine ACTH FSH LH Extracellular fluid Cytoplasm GDP Glucagon PTH TSH Calcitonin 1 2

20. Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 3 Hormone (1st messenger) binds receptor. Receptor activates G protein (G S ). G protein activates adenylate cyclase. Receptor G protein (G S ) Adenylate cyclase Hormones that act via cAMP mechanisms: Epinephrine ACTH FSH LH Extracellular fluid Cytoplasm GDP Glucagon PTH TSH Calcitonin 1 23

21. Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 4 Hormone (1st messenger) binds receptor. Receptor activates G protein (G S ). G protein activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP (2nd messenger). Receptor G protein (G S ) Adenylate cyclase Hormones that act via cAMP mechanisms: Epinephrine ACTH FSH LH Extracellular fluid Cytoplasm GDP Glucagon PTH TSH Calcitonin 1 234

22. Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 5 Hormone (1st messenger) binds receptor. Receptor activates G protein (G S ). G protein activates adenylate cyclase. cAMP acti- vates protein kinases. Adenylate cyclase converts ATP to cAMP (2nd messenger). Receptor G protein (G S ) Adenylate cyclase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Hormones that act via cAMP mechanisms: Epinephrine ACTH FSH LH Inactive protein kinase Extracellular fluid Cytoplasm Active protein kinase GDP Glucagon PTH TSH Calcitonin 1 234 5

23. Copyright © 2010 Pearson Education, Inc. Plasma Membrane Receptors and Second- Messenger Systems PIP 2 -calcium signaling mechanism Used by some amino acid–based hormones in some tissues Involves a G protein G protein activates phospholipase C enzyme

24. Copyright © 2010 Pearson Education, Inc. Plasma Membrane Receptors and Second- Messenger Systems Phospholipase splits membrane phospholipid PIP 2 into two second messengers: diacylglycerol (DAG) and IP 3 DAG activates protein kinases; IP 3 triggers release of Ca 2+ Ca 2+ alters enzymes or channels or binds to the regulatory protein calmodulin

25. Copyright © 2010 Pearson Education, Inc. Intracellular Receptors and Direct Gene Activation Steroid hormones and thyroid hormone 1.Diffuse into their target cells and bind with intracellular receptors 2.Receptor-hormone complex enters the nucleus 3.Receptor-hormone complex binds to a specific region of DNA 4.This prompts DNA transcription to produce mRNA 5.The mRNA directs protein synthesis

26. Copyright © 2010 Pearson Education, Inc. Figure 16.3 mRNA New protein DNA Hormone response elements Receptor- hormone complex Receptor protein Cytoplasm Nucleus Extracellular fluid Steroid hormone The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. The receptor- hormone complex enters the nucleus. The receptor- hormone complex binds a hormone response element (a specific DNA sequence). Binding initiates transcription of the gene to mRNA. The mRNA directs protein synthesis. Plasma membrane 1 2 3 4 5

27. Copyright © 2010 Pearson Education, Inc. Figure 16.3, step 1 Receptor- hormone complex Receptor protein Cytoplasm Nucleus Extracellular fluid Steroid hormone The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Plasma membrane 1

28. Copyright © 2010 Pearson Education, Inc. Figure 16.3, step 2 Receptor- hormone complex Receptor protein Cytoplasm Nucleus Extracellular fluid Steroid hormone The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. The receptor- hormone complex enters the nucleus. Plasma membrane 1 2

29. Copyright © 2010 Pearson Education, Inc. Figure 16.3, step 3 DNA Hormone response elements Receptor- hormone complex Receptor protein Cytoplasm Nucleus Extracellular fluid Steroid hormone The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. The receptor- hormone complex enters the nucleus. The receptor- hormone complex binds a hormone response element (a specific DNA sequence). Plasma membrane 1 2 3

30. Copyright © 2010 Pearson Education, Inc. Figure 16.3, step 4 mRNA DNA Hormone response elements Receptor- hormone complex Receptor protein Cytoplasm Nucleus Extracellular fluid Steroid hormone The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. The receptor- hormone complex enters the nucleus. The receptor- hormone complex binds a hormone response element (a specific DNA sequence). Binding initiates transcription of the gene to mRNA. Plasma membrane 1 2 3 4

31. Copyright © 2010 Pearson Education, Inc. Figure 16.3, step 5 mRNA New protein DNA Hormone response elements Receptor- hormone complex Receptor protein Cytoplasm Nucleus Extracellular fluid Steroid hormone The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. The receptor- hormone complex enters the nucleus. The receptor- hormone complex binds a hormone response element (a specific DNA sequence). Binding initiates transcription of the gene to mRNA. The mRNA directs protein synthesis. Plasma membrane 1 2 3 4 5

32. Copyright © 2010 Pearson Education, Inc. Target Cell Specificity Target cells must have specific receptors to which the hormone binds ACTH receptors are only found on certain cells of the adrenal cortex Thyroxin receptors are found on nearly all cells of the body

33. Copyright © 2010 Pearson Education, Inc. Target Cell Activation Target cell activation depends on three factors 1.Blood levels of the hormone 2.Relative number of receptors on or in the target cell 3.Affinity of binding between receptor and hormone

34. Copyright © 2010 Pearson Education, Inc. Target Cell Activation Hormones influence the number of their receptors Up-regulation—target cells form more receptors in response to the hormone Down-regulation—target cells lose receptors in response to the hormone

35. Copyright © 2010 Pearson Education, Inc. Hormones in the Blood Hormones circulate in the blood either free or bound Steroids and thyroid hormone are attached to plasma proteins All others circulate without carriers The concentration of a circulating hormone reflects: Rate of release Speed of inactivation and removal from the body

36. Copyright © 2010 Pearson Education, Inc. Hormones in the Blood Hormones are removed from the blood by Degrading enzymes Kidneys Liver Half-life—the time required for a hormone’s blood level to decrease by half

37. Copyright © 2010 Pearson Education, Inc. Interaction of Hormones at Target Cells Multiple hormones may interact in several ways 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

38. Copyright © 2010 Pearson Education, Inc. Control of Hormone Release Blood levels of hormones Are controlled by negative feedback systems Vary only within a narrow desirable range Hormones are synthesized and released in response to 1.Humoral stimuli 2.Neural stimuli 3.Hormonal stimuli

39. Copyright © 2010 Pearson Education, Inc. Humoral Stimuli Changing blood levels of ions and nutrients directly stimulates secretion of hormones Example: Ca 2+ in the blood Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca 2+ concentrations to rise and the stimulus is removed

40. Copyright © 2010 Pearson Education, Inc. Figure 16.4a (a) Humoral Stimulus Capillary (low Ca 2+ in blood) Parathyroid glands Thyroid gland (posterior view) PTH Parathyroid glands 1 Capillary blood contains low concentration of Ca 2+, which stimulates… 2 …secretion of parathyroid hormone (PTH) by parathyroid glands*

41. Copyright © 2010 Pearson Education, Inc. Neural Stimuli Nerve fibers stimulate hormone release Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines

42. Copyright © 2010 Pearson Education, Inc. Figure 16.4b (b) Neural Stimulus CNS (spinal cord) Medulla of adrenal gland Preganglionic sympathetic fibers Capillary 1 Preganglionic sympathetic fibers stimulate adrenal medulla cells… 2 …to secrete catechola- mines (epinephrine and norepinephrine)

43. Copyright © 2010 Pearson Education, Inc. Hormonal Stimuli Hormones stimulate other endocrine organs to release their hormones Hypothalamic hormones stimulate the release of most anterior pituitary hormones Anterior pituitary hormones stimulate targets to secrete still more hormones Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from the final target organs inhibit the release of the anterior pituitary hormones

44. Copyright © 2010 Pearson Education, Inc. Figure 16.4c (c) Hormonal Stimulus Hypothalamus Thyroid gland Adrenal cortex Gonad (Testis) Pituitary gland 1 The hypothalamus secretes hormones that… 2 …stimulate the anterior pituitary gland to secrete hormones that… 3 …stimulate other endocrine glands to secrete hormones

45. Copyright © 2010 Pearson Education, Inc. Nervous System Modulation The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms Example: under severe stress, the hypothalamus and the sympathetic nervous system are activated As a result, body glucose levels rise

46. Copyright © 2010 Pearson Education, Inc. The Pituitary Gland and Hypothalamus The pituitary gland (hypophysis) has two major lobes 1.Posterior pituitary (lobe): Pituicytes (glial-like supporting cells) and nerve fibers 2.Anterior pituitary (lobe) (adenohypophysis) Glandular tissue

47. Copyright © 2010 Pearson Education, Inc. Pituitary-Hypothalamic Relationships Posterior lobe A downgrowth of hypothalamic neural tissue Neural connection to the hypothalamus (hypothalamic-hypophyseal tract) Nuclei of the hypothalamus synthesize the neurohormones oxytocin and antidiuretic hormone (ADH) Neurohormones are transported to the posterior pituitary

48. Copyright © 2010 Pearson Education, Inc. Figure 16.5a 1 2 3 4 Hypothalamic neurons synthesize oxytocin and ADH. Oxytocin and ADH are transported along the hypothalamic-hypophyseal tract to the posterior pituitary. Oxytocin and ADH are stored in axon terminals in the posterior pituitary. Oxytocin and ADH are released into the blood when hypothalamic neurons fire. Paraventricular nucleus Supraoptic nucleus Optic chiasma Hypothalamus Inferior hypophyseal artery Oxytocin ADH Infundibulum (connecting stalk) Hypothalamic- hypophyseal tract Axon terminals Posterior lobe of pituitary (a) Relationship between the posterior pituitary and the hypothalamus

49. Copyright © 2010 Pearson Education, Inc. Pituitary-Hypothalamic Relationships Anterior Lobe: Originates as an out-pocketing of the oral mucosa Hypophyseal portal system Primary capillary plexus Hypophyseal portal veins Secondary capillary plexus Carries releasing and inhibiting hormones to the anterior pituitary to regulate hormone secretion

50. Copyright © 2010 Pearson Education, Inc. Figure 16.5b 1 2 3 When appropriately stimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus. Hypothalamic hormones travel through the portal veins to the anterior pituitary where they stimulate or inhibit release of hormones from the anterior pituitary. Anterior pituitary hormones are secreted into the secondary capillary plexus. Hypothalamus Hypothalamic neuron cell bodies Hypophyseal portal system Superior hypophyseal artery (b) Relationship between the anterior pituitary and the hypothalamus Anterior lobe of pituitary TSH, FSH, LH, ACTH, GH, PRL Primary capillary plexus Hypophyseal portal veins Secondary capillary plexus

51. Copyright © 2010 Pearson Education, Inc. Anterior Pituitary Hormones Growth hormone (GH) Thyroid-stimulating hormone (TSH) or thyrotropin Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL)

52. Copyright © 2010 Pearson Education, Inc. Anterior Pituitary Hormones All are proteins All except GH activate cyclic AMP second- messenger systems at their targets TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)

53. Copyright © 2010 Pearson Education, Inc. Growth Hormone (GH) Produced by somatotrophs Stimulates most cells, but targets bone and skeletal muscle Promotes protein synthesis and encourages use of fats for fuel Most effects are mediated indirectly by insulin- like growth factors (IGFs)

54. Copyright © 2010 Pearson Education, Inc. Growth Hormone (GH) GH release is regulated by Growth hormone–releasing hormone (GHRH) Growth hormone–inhibiting hormone (GHIH) (somatostatin)

55. Copyright © 2010 Pearson Education, Inc. Actions of Growth Hormone Direct action of GH Stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors Mobilizes fats, elevates blood glucose by decreasing glucose uptake and encouraging glycogen breakdown (anti-insulin effect of GH)

56. Copyright © 2010 Pearson Education, Inc. Homeostatic Imbalances of Growth Hormone Hypersecretion In children results in gigantism In adults results in acromegaly Hyposecretion In children results in pituitary dwarfism

57. Copyright © 2010 Pearson Education, Inc. Figure 16.6 Growth hormone Feedback Inhibits GHRH release Stimulates GHIH release Inhibits GH synthesis and release Anterior pituitary Liver and other tissues Indirect actions (growth- promoting) Direct actions (metabolic, anti-insulin) Insulin-like growth factors (IGFs) Extraskeletal SkeletalFat Carbohydrate metabolism Increased cartilage formation and skeletal growth Increased protein synthesis, and cell growth and proliferation Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Effects Produce Hypothalamus secretes growth hormone—releasing hormone (GHRH), and somatostatin (GHIH) Initial stimulus Physiological response Result Increases, stimulates Reduces, inhibits

58. Copyright © 2010 Pearson Education, Inc. Thyroid-Stimulating Hormone (Thyrotropin) Produced by thyrotrophs of the anterior pituitary Stimulates the normal development and secretory activity of the thyroid

59. Copyright © 2010 Pearson Education, Inc. Thyroid-Stimulating Hormone (Thyrotropin) Regulation of TSH release Stimulated by thyrotropin-releasing hormone (TRH) Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus

60. Copyright © 2010 Pearson Education, Inc. Figure 16.7 Hypothalamus Anterior pituitary Thyroid gland Thyroid hormones TSH TRH Target cells Stimulates Inhibits

61. Copyright © 2010 Pearson Education, Inc. Adrenocorticotropic Hormone (Corticotropin) Secreted by corticotrophs of the anterior pituitary Stimulates the adrenal cortex to release corticosteroids

62. Copyright © 2010 Pearson Education, Inc. Adrenocorticotropic Hormone (Corticotropin) Regulation of ACTH release Triggered by hypothalamic corticotropin- releasing hormone (CRH) in a daily rhythm Internal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRH

63. Copyright © 2010 Pearson Education, Inc. Gonadotropins Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Secreted by gonadotrophs of the anterior pituitary FSH stimulates gamete (egg or sperm) production LH promotes production of gonadal hormones Absent from the blood in prepubertal boys and girls

64. Copyright © 2010 Pearson Education, Inc. Gonadotropins Regulation of gonadotropin release Triggered by the gonadotropin-releasing hormone (GnRH) during and after puberty Suppressed by gonadal hormones (feedback)

65. Copyright © 2010 Pearson Education, Inc. Prolactin (PRL) Secreted by lactotrophs of the anterior pituitary Stimulates milk production

66. Copyright © 2010 Pearson Education, Inc. Prolactin (PRL) Regulation of PRL release Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine) Blood levels rise toward the end of pregnancy Suckling stimulates PRH release and promotes continued milk production