Chapter 18

1. Chapter 18 The Endocrine System Lecture Outline

2. Chapter 18The Endocrine System • The nervous and endocrine systems act as a coordinated interlocking supersystem, the neuroendocrine system. • The endocrine system controls body activities by releasing mediator molecules called hormones. • hormones released into the bloodstream travel throughout the body • results may take hours, but last longer • The nervous system controls body actions through nerve impulses. • certain parts release hormones into blood • rest releases neurotransmitters excite or inhibit nerve, muscle & gland cells • results in milliseconds, brief duration of effects Principles of Human Anatomy and Physiology, 11e

3. NERVOUS and ENDOCRINE SYSTEM • The nervous system causes muscles to contract or glands to secrete. The endocrine system affects virtually all body tissues by altering metabolism, regulating growth and development, and influencing reproductive processes. • Parts of the nervous system stimulate or inhibit the release of hormones. • Hormones may promote or inhibit the generation of nerve impulses. • Table 18.1 compares the characteristics of the nervous and endocrine systems. Principles of Human Anatomy and Physiology, 11e

4. General Functions of Hormones • Help regulate: • extracellular fluid • metabolism • biological clock • contraction of cardiac & smooth muscle • glandular secretion • some immune functions • Growth & development • Reproduction • Hormones have powerful effects when present in very low concentrations. Principles of Human Anatomy and Physiology, 11e

5. Endocrine Glands Defined • Exocrine glands • secrete products into ducts which empty into body cavities or body surface • sweat, oil, mucous, & digestive glands • Endocrine glands • secrete products (hormones) into bloodstream • pituitary, thyroid, parathyroid, adrenal, pineal • other organs secrete hormones as a 2nd function • hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach, liver, small intestine, skin, heart & placenta Principles of Human Anatomy and Physiology, 11e

6. Hormone Receptors • Hormones only affect target cells with specific membrane proteins called receptors Principles of Human Anatomy and Physiology, 11e

7. Hormone Receptors • Although hormones travel in blood throughout the body, they affect only specific target cells. • Target cells have specific protein or glycoprotein receptors to which hormones bind. • Receptors are constantly being synthesized and broken down. • Synthetic hormones that block the receptors for particular naturally occurring hormones are available as drugs. (Clinical Application) Principles of Human Anatomy and Physiology, 11e

8. Regulation of Hormone Receptors • Receptors are constantly being synthesized & broken down • range of 2000-100,000 receptors / target cell • Down-regulation • excess hormone leads to a decrease in number of receptors • receptors undergo endocytosis and are degraded • decreases sensitivity of target cell to hormone • Up-regulation • deficiency of hormone leads to an increase in the number of receptors • target tissue becomes more sensitive to the hormone Principles of Human Anatomy and Physiology, 11e

9. Blocking Hormone Receptors • Synthetic drugs may block receptors for naturally occurring hormones • Normally, progesterone levels drop once/month leading to menstruation. Progesterone levels are maintained when a woman becomes pregnant. • RU486 (mifepristone) binds to the receptors for progesterone preventing progesterone from sustaining the endometrium in a pregnant woman • brings on menstrual cycle • used to induce abortion Principles of Human Anatomy and Physiology, 11e

10. Circulating and Local Hormones • Hormones that travel in blood and act on distant target cells are called circulating hormones or endocrines. • Hormones that act locally without first entering the blood stream are called local hormones. • Those that act on neighboring cells are called paracrines. • Those that act on the same cell that secreted them are termed autocrines. • Figure 18.2 compares the site of action of circulating and local hormones. Principles of Human Anatomy and Physiology, 11e

11. Circulating & Local Hormones • Circulating hormones • Local hormones • paracrines • autocrines Principles of Human Anatomy and Physiology, 11e

12. Chemical Classes of Hormones - Overview • Table 18.2 provides a summary of the hormones. • Lipid-soluble hormones include the steroids, thyroid hormones, and nitric oxide, which acts as a local hormone in several tissues. • Water-soluble hormones include the amines; peptides, proteins, and glycoproteins; and eicosanoids. Principles of Human Anatomy and Physiology, 11e

13. Lipid-soluble Hormones • Steroids • lipids derived from cholesterol on SER • different functional groups attached to core of structure provide uniqueness • Thyroid hormones • tyrosine ring plus attached iodines are lipid-soluble • Nitric oxide is gas Principles of Human Anatomy and Physiology, 11e

14. Water-soluble Hormones • Amine, peptide and protein hormones • modified amino acids or amino acids put together • serotonin, melatonin, histamine, epinephrine • some glycoproteins • Eicosanoids • derived from arachidonic acid (fatty acid) • prostaglandins or leukotrienes Principles of Human Anatomy and Physiology, 11e

15. Hormone Transport in Blood • Protein hormones circulate in free form in blood • Steroid (lipid) & thyroid hormones must attach to transport proteins synthesized by liver • improve transport by making them water-soluble • slow loss of hormone by filtration within kidney • create reserve of hormone • only 0.1% to 10% of hormone is not bound to transport protein = free fraction Principles of Human Anatomy and Physiology, 11e

16. General Mechanisms of Hormone Action • Hormone binds to cell surface or receptor inside target cell • Cell may then • synthesize new molecules • change permeability of membrane • alter rates of reactions • Each target cell responds to hormone differently At liver cells---insulin stimulates glycogen synthesis At adipocytes---insulin stimulates triglyceride synthesis Principles of Human Anatomy and Physiology, 11e

17. Action of Lipid-Soluble Hormone • Lipid-soluble hormones bind to and activate receptors within cells. • The activated receptors then alter gene expression which results in the formation of new proteins. • The new proteins alter the cells activity and result in the physiological responses of those hormones. • Figure 18.3 shows this mechanism of action. Principles of Human Anatomy and Physiology, 11e

18. Hormone diffuses through phospholipid bilayer & into cell Binds to receptor turning on/off specific genes New mRNA is formed & directs synthesis of new proteins New protein alters cell’s activity Action of Lipid-Soluble Hormones Principles of Human Anatomy and Physiology, 11e

19. Action of Water-Soluble Hormones • Water-soluble hormones alter cell functions by activating plasma membrane receptors, which set off a cascade of events inside the cell. • The water-soluble hormone that binds to the cell membrane receptor is the first messenger. • A second messenger is released inside the cell where hormone stimulated response takes place. • A typical mechanism of action of a water-soluble hormone using cyclic AMP as the second messenger is seen in Figure 18.4. Principles of Human Anatomy and Physiology, 11e

20. Action of Water-Soluble Hormones • The hormone binds to the membrane receptor. • The activated receptor activates a membrane G-protein which turns on adenylate cyclase. • Adenylate cyclase converts ATP into cyclic AMP which activates protein kinases. • Protein kinases phosphorylate enzymes which catalyze reactions that produce the physiological response. • Since hormones that bond to plasma membrane receptors initiate a cascade of events, they can induce their effects at very low concentrations. Principles of Human Anatomy and Physiology, 11e

21. Action of Water-Soluble Hormones • Can not diffuse through plasma membrane • Hormone receptors are integral membrane proteins • act as first messenger • The hormone binds to the membrane receptor. • The activated receptor activates a membrane G-protein which turns on adenylate cyclase. • Adenylate cyclase converts ATP into cyclic AMP which activates protein kinases. • Protein kinases phosphorylate enzymes which catalyze reactions that produce the physiological response. Principles of Human Anatomy and Physiology, 11e

22. Water-soluble Hormones • Cyclic AMP is the 2nd messenger • kinases in the cytosol speed up/slow down physiological responses • Phosphodiesterase inactivates cAMP quickly • Cell response is turned off unless new hormone molecules arrive Principles of Human Anatomy and Physiology, 11e

23. Second Messengers • Some hormones exert their influence by increasing the synthesis of cAMP • ADH, TSH, ACTH, glucagon and epinephrine • Some exert their influence by decreasing the level of cAMP • growth hormone inhibiting hormone • Other substances can act as 2nd messengers • calcium ions • cGMP • A hormone may use different 2nd messengers in different target cells Principles of Human Anatomy and Physiology, 11e

24. Amplification of Hormone Effects • Single molecule of hormone binds to receptor • Activates 100 G-proteins • Each activates an adenylate cyclase molecule which then produces 1000 cAMP • Each cAMP activates a protein kinase, which may act upon 1000’s of substrate molecules • One molecule of epinephrine may result in breakdown of millions of glycogen molecules into glucose molecules Principles of Human Anatomy and Physiology, 11e

25. Cholera Toxin and G Proteins • Toxin is deadly because it produces massive watery diarrhea and person dies from dehydration • Toxin of cholera bacteria causes G-protein to lock in activated state in intestinal epithelium • Cyclic AMP causes intestinal cells to actively transport chloride (Na+ and water follow) into the lumen • Person die unless ions and fluids are replaced & receive antibiotic treatment Principles of Human Anatomy and Physiology, 11e

26. Hormonal Interactions • The responsiveness of a target cell to a hormone depends on the hormone’s concentration, the abundance of the target cell’s hormone receptors, and influences exerted by other hormones. • Three hormonal interactions are the • permissive effect • synergisticeffect • antagonist effect Principles of Human Anatomy and Physiology, 11e

27. Hormonal Interactions • Permissive effect • a second hormone, strengthens the effects of the first • thyroid strengthens epinephrine’s effect upon lipolysis • Synergistic effect • two hormones acting together for greater effect • estrogen & LH are both needed for oocyte production • Antagonistic effects • two hormones with opposite effects • insulin promotes glycogen formation & glucagon stimulates glycogen breakdown Principles of Human Anatomy and Physiology, 11e

28. Control of Hormone Secretion • Regulated by signals from nervous system, chemical changes in the blood or by other hormones • Negative feedback control (most common) • decrease/increase in blood level is reversed • Positive feedback control • the change produced by the hormone causes more hormone to be released • Disorders involve either hyposecretion or hypersecretion of a hormone Principles of Human Anatomy and Physiology, 11e

29. HYPOTHALAMUS AND PITUITARY GLAND • The hypothalamus is the major integrating link between the nervous and endocrine systems. • Hypothalamus receives input from cortex, thalamus, limbic system & internal organs • Hypothalamus controls pituitary gland with 9 different releasing & inhibiting hormones • The hypothalamus and the pituitary gland (hypophysis) regulate virtually all aspects of growth, development, metabolism, and homeostasis. Principles of Human Anatomy and Physiology, 11e

30. Anatomy of Pituitary Gland • The pituitary gland is located in the sella turcica of the sphenoid bone and is differentiated into the anterior pituitary (adenohypophysis), the posteriorpituitary (neurohypophysis), and pars intermedia (avascular zone in between (Figures 18.5 and 18.21b). • Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid • Infundibulum attaches it to brain • Anterior lobe = 75% • develops from roof of mouth • Posterior lobe = 25% • ends of axons of 10,000 neurons found in hypothalamus • neuroglial cells called pituicytes Principles of Human Anatomy and Physiology, 11e

31. Anterior Pituitary Gland (Adenohypophysis) • The blood supply to the anterior pituitary is from the superiorhypophyseal arteries. • Hormones of the anterior pituitary and the cells that produce the: • Human growth hormone (hGH) is secreted by somatotrophs. • Thyroid-stimulating hormone (TSH) is secreted by thyrotrophs. • Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotrophs. • Prolactin (PRL) is secreted by lactrotrophs. • Adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH) are secreted by corticotrophs. Principles of Human Anatomy and Physiology, 11e

32. Flow of Blood to Anterior Pituitary • Controlling hormones enter blood • Travel through portal veins • Enter anterior pituitary at capillaries Principles of Human Anatomy and Physiology, 11e

33. Anterior Pituitary Principles of Human Anatomy and Physiology, 11e

34. Feedback • Secretion of anterior pituitary gland hormones is regulated by hypothalamic regulating hormones and by negative feedback mechanisms (Figure 18.6, Table 18.3). Principles of Human Anatomy and Physiology, 11e

35. Negative Feedback Systems • Decrease in blood levels • Receptors in hypothalamus & thyroid • Cells activated to secrete more TSH or more T3 & T4 • Blood levels increase Principles of Human Anatomy and Physiology, 11e

36. Positive Feedback • Oxytocin stimulates uterine contractions • Uterine contractions stimulate oxytocin release Principles of Human Anatomy and Physiology, 11e

37. Human Growth Hormone and Insulin-like Growth Factors • Human growth hormone (hGH) is the most plentiful anterior pituitary hormone. • It acts indirectly on tissues by promoting the synthesis and secretion of small protein hormones called insulin-like growth factors (IGFs). • IGFs stimulate general body growth and regulate various aspects of metabolism. • Various stimuli promote and inhibit hGH production (Figure 18.7). • One symptom of excess hGH is hyperglycemia. (Clinical Application) Principles of Human Anatomy and Physiology, 11e

38. Human Growth Hormone • Produced by somatotrophs • target cells synthesize insulinlike growth • common target cells are liver, skeletal muscle, cartilage and bone • increases cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins • stimulate lipolysis in adipose so fatty acids used for ATP • retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain Principles of Human Anatomy and Physiology, 11e

39. Regulation of hGH • Low blood sugar stimulates release of GHRH from hypothalamus • anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells • High blood sugar stimulates release of GHIH from hypothalamus • less hGH from anterior pituitary, glycogen does not breakdown into glucose Principles of Human Anatomy and Physiology, 11e

40. Diabetogenic Effect of Human Growth Hormone • Excess of growth hormone • raises blood glucose concentration • pancreas releases insulin continually • beta-cell burnout • Diabetogenic effect • causes diabetes mellitis if no insulin activity can occur eventually Principles of Human Anatomy and Physiology, 11e

41. Thyroid Stimulating Hormone (TSH) • Hypothalamus regulates thyrotroph cells • Thyrotroph cells produce TSH • TSH stimulates the synthesis & secretion of T3 and T4 • Metabolic rate stimulated Principles of Human Anatomy and Physiology, 11e

42. Follicle Stimulating Hormone (FSH) • Releasing hormone from hypothalamus controls gonadotrophs • Gonadotrophs release follicle stimulating hormone • FSH functions • initiates the formation of follicles within the ovary • stimulates follicle cells to secrete estrogen • stimulates sperm production in testes Principles of Human Anatomy and Physiology, 11e

43. Luteinizing Hormone (LH) • Releasing hormones from hypothalamus stimulate gonadotrophs • Gonadotrophs produce LH • In females, LH stimulates • secretion of estrogen • ovulation of 2nd oocyte from ovary • formation of corpus luteum • secretion of progesterone • In males, LH stimulates the interstitial cells of the testes to secrete testosterone. Principles of Human Anatomy and Physiology, 11e

44. Prolactin (PRL) • Prolactin (PRL), together with other hormones, initiates and maintains milk secretion by the mammary glands. • Hypothalamus regulates lactotroph cells • Lactotrophs produce prolactin • Under right conditions, prolactin causes milk production • Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production Principles of Human Anatomy and Physiology, 11e

45. Adrenocorticotrophic Hormone • Adrenocorticotrophic hormone (ACTH) controls the production and secretion of hormones called glucocorticoids by the cortex of the adrenal gland. • Hypothalamus releasing hormones stimulate corticotrophs • Corticotrophs secrete ACTH & MSH • ACTH stimulates cells of the adrenal cortex that produce glucocorticoids Principles of Human Anatomy and Physiology, 11e

46. Melanocyte-Stimulating Hormone • Melanocyte-stimulating hormone (MSH) increases skin pigmentation although its exact role in humans is unknown. • Releasing hormone from hypothalamus increases MSH release from the anterior pituitary • Secreted by corticotroph cells • Function not certain in humans (increase skin pigmentation in frogs ) Principles of Human Anatomy and Physiology, 11e

47. Posterior Pituitary Gland (Neurohypophysis) • Although the posterior pituitary gland does not synthesize hormones, it does store and release two hormones. • Hormones made by the hypothalamus and stored in the posterior pituitary are oxytocin (OT) and antidiuretic hormone (ADH). • The neural connection between the hypothalamus and the neurohypophysis is via the hypothalamohypophyseal tract (Figure 18.8). Principles of Human Anatomy and Physiology, 11e

48. Posterior Pituitary Gland (Neurohypophysis) • Does not synthesize hormones • Consists of axon terminals of hypothalamic neurons • Neurons release two neurotransmitters into capillaries • antidiuretic hormone • oxytocin Principles of Human Anatomy and Physiology, 11e

49. Oxytocin • Two target tissues both involved in neuroendocrine reflexes • During delivery • baby’s head stretches cervix • hormone release enhances uterine muscle contraction • baby & placenta are delivered • After delivery • Oxytocin stimulates contraction of the uterus and ejection (let-down) of milk from the breasts. • Nursing a baby after delivery stimulates oxytocin release, promoting uterine contractions and the expulsion of the placenta (Clinical Application). • suckling & hearing baby’s cry stimulates milk ejection Principles of Human Anatomy and Physiology, 11e

50. Oxytocin during Labor • Stimulation of uterus by baby • Hormone release from posterior pituitary • Uterine smooth muscle contracts until birth of baby • Baby pushed into cervix, increase hormone release • More muscle contraction occurs • When baby is born, positive feedback ceases Principles of Human Anatomy and Physiology, 11e