The Endocrine System

1. The Endocrine System

2. The Endocrine System • Second messenger system of the body • Uses chemical messages (hormones) that are released into the blood • Hormones control several major processes • Reproduction • Growth and development • Mobilization of body defenses • Maintenance of much of homeostasis • Regulation of metabolism

3. Hormone Overview • Hormones are produced by specialized cells • Cells secrete hormones into extracellular fluids • Blood transfers hormones to target sites • These hormones regulate the activity of other cells

5. Mechanisms of Hormone Action • Hormones affect only certain tissues or organs (target cells or organs) • Target cells must have specific protein receptors • Hormone binding influences the working of the cells

7. Effects Caused by Hormones • Changes in plasma membrane permeability or electrical state • Synthesis of proteins, such as enzymes • Activation or inactivation of enzymes • Stimulation of mitosis

8. The Chemistry of Hormones • Amino acid-based hormones • Proteins • Peptides • Amines • Steroids – made from cholesterol • Prostaglandins – made from highly active lipids

9. Steroid Hormone Action • Diffuse through the plasma membrane of target cells • Enter the nucleus • Bind to a specific protein within the nucleus • Bind to specific sites on the cell’s DNA • Activate genes that result in synthesis of new proteins

10. Steroid Hormone Action PRESS TO PLAY STEROID HORMONE ANIMATION Figure 9.1a

11. Nonsteroid Hormone Action • Hormone binds to a membrane receptor • Hormone does not enter the cell • Sets off a series of reactions that activates an enzyme • Catalyzes a reaction that produces a second messenger molecule • Oversees additional intracellular changes to promote a specific response

12. Nonsteroid Hormone Action PRESS TO PLAY NONSTEROID HORMONE ANIMATION Figure 9.1b

13. 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 • Humoral stimuli • Neural stimuli • Hormonal stimuli

14. Humoral Stimuli • Changing blood levels of ions and nutrients directly stimulates secretion of hormones • Examples:

15. Humoral Stimuli (a) Humoral Stimulus Capillary blood contains low concentration of Ca2+, which stimulates… 1 • Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) • PTH causes Ca2+ concentrations to rise and the stimulus is removed Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroidglands PTH …secretion of parathyroid hormone (PTH) by parathyroid glands* 2 Figure 16.4a

16. Neural Stimuli • Nerve fibers stimulate hormone release • Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines Figure 16.4b (b) Neural Stimulus Preganglionic sympathetic fibers stimulate adrenal medulla cells… 1 CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary …to secrete catechola- mines (epinephrine and norepinephrine) 2

17. 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 Figure 16.4c (c) Hormonal Stimulus The hypothalamus secretes hormones that… 1 Hypothalamus …stimulate the anterior pituitary gland to secrete hormones that… 2 Pituitary gland Thyroid gland Adrenal cortex Gonad (Testis) …stimulate other endocrine glands to secrete hormones 3

18. Location of Major Endrocrine Organs Figure 9.3

19. Pituitary Gland • Size of a grape • Hangs by a stalk from the hypothalamus • Protected by the sphenoid bone • Has two functional lobes • Anterior pituitary – glandular tissue • Posterior pituitary – nervous tissue

20. The Pituitary Gland and Hypothalamus • “Master gland”, hypophysis, 600 mg (!) • In hypophyseal fossa, above sella turcica of sphenoid bone • Posterior pituitary (neurohypophysis) • Anterior pituitary (adenohypophysis)

21. Pituitary-Hypothalamic Relationships • Posterior lobe (neurohypophysis) • 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

22. Paraventricular nucleus Hypothalamus 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). Posterior lobe of pituitary Optic chiasma Supraoptic nucleus Infundibulum (connecting stalk) 2 Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary. Inferior hypophyseal artery Hypothalamic- hypophyseal tract Axon terminals 3 Oxytocin and ADH are stored in axon terminals in the posterior pituitary. Posterior lobe of pituitary 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. Oxytocin ADH

23. Pituitary-Hypothalamic Relationships • Anterior Lobe (adenohypophysis): • 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

24. Hormones of the Posterior Pituitary • Oxytocin • Stimulates contractions of the uterus during labor • Causes milk ejection • Antidiuretic hormone (ADH) • Can inhibit urine production • In large amounts, causes vasoconstriction leading to increased blood pressure (vasopressin)

25. 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) • Growth hormone (GH) • Thyroid-stimulating hormone (TSH) or thyrotropin • Adrenocorticotropic hormone (ACTH) • Follicle-stimulating hormone (FSH) • Luteinizing hormone (LH) • Prolactin (PRL)

26. Hypothalamus Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. Anterior lobe of pituitary Superior hypophyseal artery 1 When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus. 2 Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary. Hypophyseal portal system • Primary capillary plexus A portal system is two capillary plexuses (beds) connected by veins. 3 In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation. • Hypophyseal portal veins • Secondary capillary plexus GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary

27. Hormones of the Anterior Pituitary Figure 9.4

28. Growth Hormone (GH) • General metabolic hormone • Major effects are directed to growth of skeletal muscles and long bones • Causes amino acids to be built into proteins • Causes fats to be broken down for a source of energy

29. Growth Hormone (GH or Somatotropin) Hypothalamus secretes growth hormone—releasing hormone (GHRH), and somatostatin (GHIH) Inhibits GHRH release Stimulates GHIH release Feedback Anterior pituitary • 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 (especially IGF-1) Inhibits GH synthesis and release Growth hormone Direct actions (metabolic, anti-insulin) Indirect actions (growth- promoting) Liver and other tissues Produce Insulin-like growth factors (IGF-1) Effects Effects Carbohydrate metabolism Extraskeletal Skeletal Fat Increases, stimulates Reduces, inhibits Increased protein synthesis, and cell growth and proliferation Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Increased cartilage formation and skeletal growth Initial stimulus Physiological response Result Figure 16.6

30. Thyroid Gland Figure 16.8

31. Thyroid Gland • Found at the base of the throat • Consists of two lobes and a connecting isthmus • Produces two hormones • Thyroid hormone • Calcitonin

32. Thyroid Hormone (TH) • Major metabolic hormone • Increases metabolic rate and heat production (calorigenic effect) • Plays a role in • Regulation of tissue growth • Development of skeletal and nervous systems • Reproductive capabilities • Actually two related compounds • T4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms • T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms Affects virtually every cell in body

33. Thyroid Hormone • Major metabolic hormone • Composed of two active iodine-containing hormones • Thyroxine (T4) – secreted by thyroid follicles • Triiodothyronine (T3) – conversion of T4 at target tissues

34. Transport and Regulation of TH • T4 and T3 are transported by thyroxine-binding globulins (TBGs) • Both bind to target receptors, but T3 is ten times more active than T4 • Peripheral tissues convert T4 to T3

35. Regulation of TH • Negative feedback regulation of TH release • Rising TH levels provide negative feedback inhibition on release of TSH • Hypothalamic thyrotropin-releasing hormone (TRH) can overcome the negative feedback during pregnancy or exposure to cold Hypothalamus TRH Anterior pituitary TSH Thyroid gland Thyroid hormones Stimulates Target cells Inhibits Figure 16.7

36. Homeostatic Imbalances of TH • Hyposecretion in adults—myxedema; endemic goiter if due to lack of iodine • Hyposecretion in infants—cretinism • Hypersecretion—Graves’ disease • Autoimmune disease: body produces antibodies that activate TH-secreting cells by mimicking TSH • Exophthalmos Figure 16.10

37. Calcitonin • Decreases blood calcium levels by causing its deposition on bone • Antagonistic to parathyroid hormone Figure 9.9

38. Parathyroid Glands • Tiny masses on the posterior of the thyroid • Secrete parathyroid hormone • Stimulate osterclasts to remove calcium from bone • Stimulate the kidneys and intestine to absorb more calcium • Raise calcium levels in the blood

39. Parathyroid Glands Usually four (up to eight) tiny glands embedded in the posterior aspect of the thyroid Pharynx (posterior aspect) Chief cells (secrete parathyroid hormone) Thyroid gland Parathyroid glands Oxyphil cells Esophagus Trachea Capillary (a) (b) Figure 16.11

40. Parathyroid Glands • Four to eight tiny glands embedded in the posterior aspect of the thyroid • Contain oxyphil cells (function unknown) and chief cells that secrete parathyroid hormone (PTH) or parathormone • PTH—most important hormone in Ca2+ homeostasis

41. Hypocalcemia (low blood Ca2+) PTH is most important hormone for calcium homeostasis PTH release from parathyroid gland Increases blood calcium levels 3 ways Activation of vitamin D by kidney Ca2+ reabsorption in kidney tubule Osteoclast activity in bone causes Ca2+ and PO43- release into blood Ca2+ absorption from food in small intestine Ca2+ in blood Initial stimulus Physiological response Result

42. Prolactin (PRL) • Secreted by lactotrophs of the anterior pituitary • Stimulates milk production, slowly and long term • Regulation of PRL release • Primarily controlled by prolactin-inhibiting hormone (PIH) (now known to be dopamine) • Blood levels rise toward the end of pregnancy • Suckling stimulates PRH release and promotes continued milk production

43. Adrenal (Suprarenal) Glands Capsule • Paired, pyramid-shaped organs atop the kidneys • Structurally and functionally, they are two glands in one • Adrenal medulla—nervous tissue; part of the sympathetic nervous system • Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids Zona glomerulosa Zona fasciculata Adrenal gland Cortex • Medulla • Cortex Zona reticularis Kidney Adrenal medulla Medulla (a) Drawing of the histology of the adrenal cortex and a portion of the adrenal medulla

44. Adrenal Glands • Two glands • Cortex – outer glandular region in three layers • Medulla – inner neural tissue region • Sits on top of the kidneys

45. Adrenal Cortex Capsule Zona glomerulosa mineralocorticoids Zona fasciculata Adrenal gland glucocorticoids Cortex • Medulla • Cortex Zona reticularis Kidney sex hormones, or glucocorticoids Adrenal medulla Medulla (a) Drawing of the histology of the adrenal cortex and a portion of the adrenal medulla Figure 16.13a

46. Mineralocorticoids • Regulate electrolytes (primarily Na+ and K+) in ECF • Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions • Importance of K+: sets RMP of cells • Aldosterone is the most potent mineralocorticoid • Stimulates Na+ reabsorption and water retention by the kidneys; elimination of K+

47. Mechanisms of Aldosterone Secretion • Renin-angiotensin mechanism: decreased blood pressure stimulates kidneys to release renin, triggers formation of angiotensin II, a potent stimulator of aldosterone release • Plasma concentration of K+: Increased K+ directly influences the zona glomerulosa cells to release aldosterone • ACTH: causes small increases of aldosterone during stress • Atrial natriuretic peptide (ANP): inhibits renin and aldosterone secretion, to decrease blood pressure

48. Aldosteronism—hypersecretion due to adrenal tumors • Hypertension and edema due to excessive Na+ • Excretion of K+ leading to abnormal function of neurons and muscle Primary regulators Other factors Blood volume and/or blood pressure K+in blood Stress Blood pressure and/or blood volume Hypo- thalamus Heart Kidney CRH Direct stimulating effect Anterior pituitary Renin Initiates cascade that produces Atrial natriuretic peptide (ANP) ACTH Angiotensin II Inhibitory effect Zona glomerulosa of adrenal cortex Enhanced secretion of aldosterone Targets kidney tubules Absorption of Na+ and water; increased K+ excretion Blood volume and/or blood pressure Figure 16.14

49. Glucocorticoids (Cortisol) • Keep blood sugar levels relatively constant • Maintain blood pressure by increasing the action of vasoconstrictors • Cortisol(hydrocortisone) is the only significant glucocorticoid in humans • Released in response to ACTH, patterns of eating and activity, and stress • Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins • Promotes rises in blood glucose, fatty acids, and amino acids – saves glucose for brain

50. Homeostatic Imbalances of Glucocorticoids • Hypersecretion—Cushing’s syndrome • Depresses cartilage and bone formation • Inhibits inflammation • Depresses the immune system • Promotes changes in cardiovascular, neural, and gastrointestinal function • Hyposecretion—Addison’s disease • Also involves deficits in mineralocorticoids • Decrease in glucose and Na+ levels • Weight loss, severe dehydration, and hypotension