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1 Principles of Human Anatomy and Physiology, 11e1 Chapter 18 The Endocrine System Lecture Outline

2 Principles of Human Anatomy and Physiology, 11e2 Chapter 18 The 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

3 Principles of Human Anatomy and Physiology, 11e3 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.

4 Principles of Human Anatomy and Physiology, 11e4 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.

5 Principles of Human Anatomy and Physiology, 11e5 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

6 Principles of Human Anatomy and Physiology, 11e6 Hormone Receptors Hormones only affect target cells with specific membrane proteins called receptors

7 Principles of Human Anatomy and Physiology, 11e7 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)

8 Principles of Human Anatomy and Physiology, 11e8 Regulation of Hormone Receptors Receptors are constantly being synthesized & broken down –range of ,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

9 Principles of Human Anatomy and Physiology, 11e9 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

10 Principles of Human Anatomy and Physiology, 11e10 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.

11 Principles of Human Anatomy and Physiology, 11e11 Circulating & Local Hormones Circulating hormones Local hormones –paracrines –autocrines

12 Principles of Human Anatomy and Physiology, 11e12 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.

13 Principles of Human Anatomy and Physiology, 11e13 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

14 Principles of Human Anatomy and Physiology, 11e14 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

15 Principles of Human Anatomy and Physiology, 11e15 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

16 Principles of Human Anatomy and Physiology, 11e16 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

17 Principles of Human Anatomy and Physiology, 11e17 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.

18 Principles of Human Anatomy and Physiology, 11e18 Action of Lipid-Soluble Hormones 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

19 Principles of Human Anatomy and Physiology, 11e19 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.

20 Principles of Human Anatomy and Physiology, 11e20 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 bind to plasma membrane receptors initiate a cascade of events, they can induce their effects at very low concentrations.

21 Principles of Human Anatomy and Physiology, 11e21 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.

22 Principles of Human Anatomy and Physiology, 11e22 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

23 Principles of Human Anatomy and Physiology, 11e23 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

24 Principles of Human Anatomy and Physiology, 11e24 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

25 Principles of Human Anatomy and Physiology, 11e25 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

26 Principles of Human Anatomy and Physiology, 11e26 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 –synergistic effect –antagonist effect

27 Principles of Human Anatomy and Physiology, 11e27 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

28 Principles of Human Anatomy and Physiology, 11e28 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

29 Principles of Human Anatomy and Physiology, 11e29 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.

30 Principles of Human Anatomy and Physiology, 11e30 The pituitary gland is located in the sella turcica of the sphenoid bone and is differentiated into the anterior pituitary (adenohypophysis), the posterior pituitary (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 Anatomy of Pituitary Gland

31 Principles of Human Anatomy and Physiology, 11e31 Anterior Pituitary Gland (Adenohypophysis) The blood supply to the anterior pituitary is from the superior hypophyseal 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.

32 Principles of Human Anatomy and Physiology, 11e32 Flow of Blood to Anterior Pituitary Controlling hormones enter blood Travel through portal veins Enter anterior pituitary at capillaries

33 Principles of Human Anatomy and Physiology, 11e33 Anterior Pituitary

34 Principles of Human Anatomy and Physiology, 11e34 Feedback Secretion of anterior pituitary gland hormones is regulated by hypothalamic regulating hormones and by negative feedback mechanisms (Figure 18.6, Table 18.3).

35 Principles of Human Anatomy and Physiology, 11e35 Negative Feedback Systems Decrease in blood levels Receptors in hypothalamus & thyroid Cells activated to secrete more TSH or more T3 & T4 Blood levels increase

36 Principles of Human Anatomy and Physiology, 11e36 Positive Feedback Oxytocin stimulates uterine contractions Uterine contractions stimulate oxytocin release

37 Principles of Human Anatomy and Physiology, 11e37 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)

38 Principles of Human Anatomy and Physiology, 11e38 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

39 Principles of Human Anatomy and Physiology, 11e39 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

40 Principles of Human Anatomy and Physiology, 11e40 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

41 Principles of Human Anatomy and Physiology, 11e41 Thyroid Stimulating Hormone (TSH) Hypothalamus regulates thyrotroph cells Thyrotroph cells produce TSH TSH stimulates the synthesis & secretion of T3 and T4 Metabolic rate stimulated

42 Principles of Human Anatomy and Physiology, 11e42 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

43 Principles of Human Anatomy and Physiology, 11e43 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.

44 Principles of Human Anatomy and Physiology, 11e44 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

45 Principles of Human Anatomy and Physiology, 11e45 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

46 Principles of Human Anatomy and Physiology, 11e46 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 )

47 Principles of Human Anatomy and Physiology, 11e47 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).

48 Principles of Human Anatomy and Physiology, 11e48 Posterior Pituitary Gland (Neurohypophysis) Does not synthesize hormones Consists of axon terminals of hypothalamic neurons Neurons release two neurotransmitters into capillaries –antidiuretic hormone –oxytocin

49 Principles of Human Anatomy and Physiology, 11e49 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

50 Principles of Human Anatomy and Physiology, 11e50 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

51 Principles of Human Anatomy and Physiology, 11e51 ADH Antidiuretic hormone stimulates water reabsorption by the kidneys and arteriolar constriction. The effect of ADH is to decrease urine volume and conserve body water. ADH is controlled primarily by osmotic pressure of the blood (Figure 18.9).

52 Principles of Human Anatomy and Physiology, 11e52 Antidiuretic Hormone (ADH) Known as vasopressin Functions –decrease urine production –decrease sweating –increase BP

53 Principles of Human Anatomy and Physiology, 11e53 Regulation of ADH Dehydration –ADH released Overhydration –ADH inhibited

54 Principles of Human Anatomy and Physiology, 11e54 THYROID GLAND - Overview The thyroid gland is located just below the larynx and has right and left lateral lobes (Figure 18.10a). Histologically, the thyroid consists of the thyroid follicles composed of follicular cells, which secrete the thyroid hormones thyroxine (T 4 ) and triiodothyronine (T 3 ), and parafollicular cells, which secrete calcitonin (CT) (Figures 18.10b and 18.13c).

55 Principles of Human Anatomy and Physiology, 11e55 Thyroid Gland On each side of trachea is lobe of thyroid Weighs 1 oz & has rich blood supply

56 Principles of Human Anatomy and Physiology, 11e56 Histology of Thyroid Gland Follicle = sac of stored hormone (colloid) surrounded by follicle cells that produced it –T3 & T4 Inactive cells are short In between cells called parafollicular cells – produce calcitonin

57 Principles of Human Anatomy and Physiology, 11e57 Photomicrograph of Thyroid Gland

58 Principles of Human Anatomy and Physiology, 11e58 Formation, Storage, and Release of Thyroid Hormones Thyroid hormones are synthesized from iodine and tyrosine within a large glycoprotein molecule called thyroglobulin (TGB) and are transported in the blood by plasma proteins, mostly thyroxine-binding globulin (TBG). The formation, storage, and release steps include –iodide trapping, –synthesis of thyroglobulin, –oxidation of iodide, –iodination of tyrosine, –coupling of T 1 and T 2, –pinocytosis and digestion of colloid, –secretion of thyroid hormones, and transport in blood (Figure 18.11).

59 Principles of Human Anatomy and Physiology, 11e59 Formation of Thyroid Hormone Iodide trapping by follicular cells Synthesis of thyroglobulin (TGB) Release of TGB into colloid Iodination of tyrosine in colloid Formation of T3 & T4 by combining T1 and T2 together Uptake & digestion of TGB by follicle cells Secretion of T3 & T4 into blood

60 Principles of Human Anatomy and Physiology, 11e60 Actions of Hormones from Thyroid Gland T3 & T4 –thyroid hormones responsible for our metabolic rate, synthesis of protein, breakdown of fats, use of glucose for ATP production Calcitonin –responsible for building of bone & stops reabsorption of bone (lowers blood levels of Calcium)

61 Principles of Human Anatomy and Physiology, 11e61 Control of T3 & T4 Secretion Negative feedback system Low blood levels of hormones stimulate hypothalamus It stimulates pituitary to release TSH TSH stimulates gland to raise blood levels

62 Principles of Human Anatomy and Physiology, 11e62 PARATHYROID GLANDS The parathyroid glands are embedded on the posterior surfaces of the lateral lobes of the thyroid –principal cells produce parathyroid hormone –oxyphil cells … function is unknown (Figure 18.13). Parathyroid hormone (PTH) regulates the homeostasis of calcium and phosphate increase blood calcium level decrease blood phosphate level –increases the number and activity of osteoclasts –increases the rate of Ca +2 and Mg +2 from reabsorption from urine and inhibits the reabsorption of HPO 4 -2 so more is secreted in the urine –promotes formation of calcitriol, which increases the absorption of Ca +2, Mg +2,and HPO 4 -2 from the GI tract

63 Principles of Human Anatomy and Physiology, 11e63 Parathyroid Glands 4 pea-sized glands found on back of thyroid gland

64 Principles of Human Anatomy and Physiology, 11e64 Histology of Parathyroid Gland Principal cells produce parathyroid hormone (PTH) Oxyphil cell function is unknown

65 Principles of Human Anatomy and Physiology, 11e65 Blood Calcium Blood calcium level directly controls the secretion of calcitonin and parathyroid hormone via negative feedback loops that do not involve the pituitary gland (Figure 18.14). Table 18.7 summarizes the principal actions and control of secretion of parathyroid hormone.

66 Principles of Human Anatomy and Physiology, 11e66 Regulation of Calcium Blood Levels High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CT

67 Principles of Human Anatomy and Physiology, 11e67 Adrenal Glands The adrenal glands are located superior to the kidneys (Figure 18.15) 3 x 3 x 1 cm in size and weighs 5 grams consists of an outer cortex and an inner medulla. –Cortex produces 3 different types of hormones from 3 zones of cortex –Medulla produces epinephrine & norepinephrine

68 Principles of Human Anatomy and Physiology, 11e68 Adrenal Cortex The adrenal cortex is divided into three zones, each of which secretes different hormones (Figure 18.15). –The zona glomerulosa (outer zone) secretes mineralocorticoids. –The zona fasciculata (middle zone) secretes glucocorticoids. –The zona reticularis (inner zone) secretes androgens.

69 Principles of Human Anatomy and Physiology, 11e69 Histology of Adrenal Gland Cortex –3 zones Medulla

70 Principles of Human Anatomy and Physiology, 11e70 Cortex derived from mesoderm Medulla derived from ectoderm Structure of Adrenal Gland

71 Principles of Human Anatomy and Physiology, 11e71 Mineralocorticoids 95% of hormonal activity due to aldosterone Functions –increase reabsorption of Na+ with Cl-, bicarbonate and water following it –promotes excretion of K+ and H+ Hypersecretion = tumor producing aldosteronism –high blood pressure caused by retention of Na+ and water in blood

72 Principles of Human Anatomy and Physiology, 11e72 Regulation of Aldosterone

73 Principles of Human Anatomy and Physiology, 11e73 Glucocorticoids 95% of hormonal activity is due to cortisol Functions = help regulate metabolism –increase rate of protein catabolism & lipolysis –conversion of amino acids to glucose –stimulate lipolysis –provide resistance to stress by making nutrients available for ATP production –raise BP by vasoconstriction –anti-inflammatory effects reduced (skin cream) reduce release of histamine from mast cells decrease capillary permeability depress phagocytosis

74 Principles of Human Anatomy and Physiology, 11e74 Regulation of Glucocorticoids Negative feedback

75 Principles of Human Anatomy and Physiology, 11e75 Androgens from Zona Reticularis Small amount of male hormone produced –insignificant in males –may contribute to sex drive in females –is converted to estrogen in postmenopausal females

76 Principles of Human Anatomy and Physiology, 11e76 Adrenal Medulla Chromaffin cells receive direct innervation from sympathetic nervous system –develop from same tissue as postganglionic neurons Produce epinephrine & norepinephrine Hormones are sympathomimetic –effects mimic those of sympathetic NS –cause fight-flight behavior Acetylcholine increase hormone secretion by adrenal medulla

77 Principles of Human Anatomy and Physiology, 11e77 PANCREATIC ISLETS The pancreas is a flattened organ located posterior and slightly inferior to the stomach and can be classified as both an endocrine and an exocrine gland (Figure 18.18). Histologically, it consists of pancreatic islets or islets of Langerhans (Figure 18.19) and clusters of cells (acini) (enzyme-producing exocrine cells).

78 Principles of Human Anatomy and Physiology, 11e78 Anatomy of Pancreas Organ (5 inches) consists of head, body & tail Cells (99%) in acini produce digestive enzymes Endocrine cells in pancreatic islets produce hormones

79 Principles of Human Anatomy and Physiology, 11e79 Cell Organization in Pancreas Exocrine acinar cells surround a small duct Endocrine cells secrete near a capillary

80 Principles of Human Anatomy and Physiology, 11e80 Histology of the Pancreas 1 to 2 million pancreatic islets Contains 4 types of endocrine cells

81 Principles of Human Anatomy and Physiology, 11e81 Cell Types in the Pancreatic Islets Alpha cells (20%) produce glucagon Beta cells (70%) produce insulin Delta cells (5%) produce somatostatin F cells produce pancreatic polypeptide

82 Principles of Human Anatomy and Physiology, 11e82 Regulation Regulation of glucagon and insulin secretion is via negative feedback mechanisms (Figure 18.19). –Low blood glucose stimulates release of glucagon –High blood glucose stimulates secretion of insulin Table 18.9 summarizes the hormones produced by the pancreas, their principal actions, and control of secretion.

83 Principles of Human Anatomy and Physiology, 11e83 Ovaries and Testes Ovaries –estrogen, progesterone, relaxin & inhibin –regulate reproductive cycle, maintain pregnancy & prepare mammary glands for lactation Testes –produce testosterone –regulate sperm production & 2nd sexual characteristics Table summarizes the hormones produced by the ovaries and testes and their principal actions.

84 Principles of Human Anatomy and Physiology, 11e84 Pineal Gland Small gland attached to 3rd ventricle of brain Consists of pinealocytes & neuroglia Melatonin responsible for setting of biological clock Jet lag & SAD treatment is bright light

85 Principles of Human Anatomy and Physiology, 11e85 Effect of Light on Pineal Gland Melatonin secretion producing sleepiness occurs during darkness due to lack of stimulation from sympathetic ganglion

86 Principles of Human Anatomy and Physiology, 11e86 Seasonal Affective Disorder and Jet Lag Depression that occurs during winter months when day length is short Due to overproduction of melatonin Therapy –exposure to several hours per day of artificial light as bright as sunlight –speeds recovery from jet lag

87 Principles of Human Anatomy and Physiology, 11e87 Thymus Gland Important role in maturation of T cells Hormones produced by gland promote the proliferation & maturation of T cells –thymosin –thymic humoral factor –thymic factor –thymopoietin

88 Principles of Human Anatomy and Physiology, 11e88 OTHER HORMONES and GROWTH FACTORS Several body tissues other than those usually classified as endocrine glands also contain endocrine tissue and thus secrete hormones. Table summarizes these hormones and their actions.

89 Principles of Human Anatomy and Physiology, 11e89 Eicosanoids Local hormones released by all body cells alter the production of second messengers, such as cyclic AMP –Leukotrienes influence WBCs & inflammation –Prostaglandins alter: smooth muscle contraction, glandular secretion, blood flow, platelet function, nerve transmission, metabolism. Aspirin and related nonsteroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen and acetaminophen, inhibit a key enzyme in prostaglandin synthesis and are used to treat a wide variety of inflammatory disorders.

90 Principles of Human Anatomy and Physiology, 11e90 Nonsteroidal Anti-inflammatory Drugs Answer to how aspirin or ibuprofen works was discovered in 1971 –inhibit a key enzyme in prostaglandin synthesis without affecting the synthesis of leukotrienes Treat a variety of inflammatory disorders –rheumatoid arthritis Usefulness of aspirin to treat fever & pain implies prostaglandins are responsible for those symptoms

91 Principles of Human Anatomy and Physiology, 11e91 Growth Factors Substances with mitogenic qualities –cause cell growth from cell division Many act locally as autocrines or paracrines Selected list of growth factors (Table 18.12) –epidermal growth factor (EGF), –platelet-derived growth factor (PDGF), –fibroblast growth factor (FGF), –nerve growth factor (NGF), –tumor angiogenesis factors (TAFs), –Insulin-like growth factor (IFG), –cytokines

92 Principles of Human Anatomy and Physiology, 11e92 STRESS RESPONSE The stimuli that produce the general adaptation syndrome are called stressors. Stressors include almost any disturbance: heat or cold, surgical operations, poisons, infections, fever, and strong emotional responses. Stages of the General Adaptation Syndrome

93 Principles of Human Anatomy and Physiology, 11e93 Stress & General Adaptation Syndrome Stress response is set of bodily changes called general adaptation syndrome (GAS) Any stimulus that produces a stress response is called a stressor Stress resets the body to meet an emergency –eustress is productive stress & helps us prepare for certain challenges –distress type levels of stress are harmful lower our resistance to infection

94 Principles of Human Anatomy and Physiology, 11e94 General Adaptation Syndrome

95 Principles of Human Anatomy and Physiology, 11e95 Alarm Reaction (Fight-or-Flight) The alarm reaction is initiated by nerve impulses from the hypothalamus to the sympathetic division of the autonomic nervous system and adrenal medulla (Figure 18.20a). Dog attack –increases circulation –promote catabolism for energy production –promotes ATP synthesis –nonessential body functions are inhibited digestive, urinary & reproductive

96 Principles of Human Anatomy and Physiology, 11e96 Resistance Reaction Initiated by hypothalamic releasing hormones (long-term reaction to stress) –corticotropin, growth hormone & thyrotropin releasing hormones Results –increased secretion of aldosterone acts to conserve Na+ (increases blood pressure) and eliminate H+ –increased secretion of cortisol so protein catabolism is increased & other sources of glucose are found –increase thyroid hormone to increase metabolism Allow body to continue to fight a stressor Glucocorticoids are produced in high concentrations during stress. They create many distinct physiological effects.

97 Principles of Human Anatomy and Physiology, 11e97 Exhaustion Exhaustion is caused mainly by loss of potassium, depletion of adrenal glucocorticoids, and weakened organs. If stress is too great, it may lead to death. –Resources of the body have become depleted –Resistance stage can not be maintained –Prolonged exposure to resistance reaction hormones wasting of muscle suppression of immune system ulceration of the GI tract failure of the pancreatic beta cells

98 Principles of Human Anatomy and Physiology, 11e98 Stress and Disease Stress can lead to disease by inhibiting the immune system –gastritis, ulcerative colitis, irritable bowel syndrome, peptic ulcers, hypertension, asthma, rheumatoid arthritis, migraine headaches, anxiety, and depression. people under stress are at a greater risk of developing chronic disease or of dying prematurely Interleukin - 1 –link between stress and immunity –secreted by macrophages; stimulates secretion of ACTH –stimulates production of immune substances –feedback control since immune substance suppress the formation of interleukin-1

99 Principles of Human Anatomy and Physiology, 11e99 DEVELOPMENTAL ANATOMY OF THE ENDOCRINE SYSTEM The pituitary gland originates from two different regions of the ectoderm. The anterior pituitary derives from the neurohypophyseal bud, located on the floor of the hypothalamus (Figure 18.21). The anterior pituitary is derived from an outgrowth of ectoderm from the mouth called the hypophyseal (Rathke’s) pouch. The thyroid gland develops as a midventral outgrowth of endoderm, called the thyroid diverticulum, from the floor of the pharynx at the level of the second pair of pharyngeal pouches. Parathyroid glands develop from endoderm as outgrowths from the third and fourth pharyngeal pouches.

100 Principles of Human Anatomy and Physiology, 11e100 Thyroid develops ---floor of pharynx 2nd pouch Parathyroid & thymus --3 & 4 pharyngeal pouches Pancreas from foregut Development of the Endocrine System

101 Principles of Human Anatomy and Physiology, 11e101 Development of Pituitary Gland Events occurring between 5 and 16 weeks of age

102 Principles of Human Anatomy and Physiology, 11e102 DEVELOPMENTAL ANATOMY OF THE ENDOCRINE SYSTEM The adrenal cortex is derived from intermediate mesoderm from the same region that produces the gonads. The adrenal medulla is ectodermal in origin and derives from the neural crest, which also gives rise to sympathetic ganglion and other nervous system structures (Figure b). The pancreas develops from the outgrowth of endoderm from the part of the foregut that later becomes the duodenum (Figure 29.12c). The pineal gland arises as an outgrowth between the thalamus and colliculi, from ectoderm associated with the diencephalon (Figure 14.26). The thymus gland arises from endoderm of the third pharyngeal pouch.

103 Principles of Human Anatomy and Physiology, 11e103 Aging and the Endocrine System Production of human growth hormone decreases –muscle atrophy Production of TSH increase with age to try and stimulate thyroid –decrease in metabolic rate, increase in body fat & hypothyroidism Thymus after puberty is replaced with adipose Adrenal glands produce less cortisol & aldosterone Receptor sensitivity to glucose declines Ovaries no longer respond to gonadotropins –decreased output of estrogen (osteoporosis & atherosclerosis)

104 Principles of Human Anatomy and Physiology, 11e104 DISORDERS: HOMEOSTATIC IMBALANCES

105 Principles of Human Anatomy and Physiology, 11e105 Diabetes Insipidus Dysfunction of the posterior pituitary Hyposecretion of ADH –excretion of large amounts of dilute urine and subsequent dehydration and thirst

106 Principles of Human Anatomy and Physiology, 11e106 Pituitary Gland Disorders Hyposecretion during childhood = pituitary dwarfism (proportional, childlike body) Hypersecretion during childhood = giantism –very tall, normal proportions Hypersecretion as adult = acromegaly –growth of hands, feet, facial features & thickening of skin

107 Principles of Human Anatomy and Physiology, 11e107 Thyroid Gland Disorders Hyposecretion during infancy results in dwarfism & retardation called cretinism Hypothyroidism in adult produces sensitivity to cold, low body temp. weight gain & mental dullness Hyperthyroidism (Grave’s disease) –weight loss, nervousness, tremor & exophthalmos (edema behind eyes) Goiter = enlarged thyroid (dietary)

108 Principles of Human Anatomy and Physiology, 11e108 Parathyroid Gland Disorders Hypoparathyroidism results in muscle tetany. Hyperparathyroidism produces osteitis fibrosa cystica

109 Principles of Human Anatomy and Physiology, 11e109 Adrenal Gland Disorders - Tumor –Pheochromocytomas, benign tumors of the adrenal medulla, cause hypersecretion of medullary hormones and a prolonged fight-or-flight response.

110 Principles of Human Anatomy and Physiology, 11e110 Adrenal Gland Disorders - Cushing’s Syndrome Hypersecretion of glucocorticoids Redistribution of fat, spindly arms & legs due to muscle loss Wound healing is poor, bruise easily

111 Principles of Human Anatomy and Physiology, 11e111 Adrenal Gland Disorders - Addison’s disease Hyposecretion of glucocorticoids –hypoglycemia, muscle weakness, low BP, dehydration due to decreased Na+ in blood –mimics skin darkening effects of MSH –potential cardiac arrest

112 Principles of Human Anatomy and Physiology, 11e112 Pancreatic Disorders Diabetes Mellitus –This is a group of disorders caused by an inability to produce or use insulin. Type I diabetes or insulin-dependent diabetes mellitus is caused by an absolute deficiency of insulin. Type II diabetes or insulin-independent diabetes is caused by a down-regulation of insulin receptors. –excessive urine production (polyuria) –excessive thirst (polydipsia) –excessive eating (polyphagia) Hyperinsulinism results when too much insulin is present –causes hypoglycemia and possibly insulin shock

113 Principles of Human Anatomy and Physiology, 11e113 end

114 Principles of Human Anatomy and Physiology, 11e114 Photographs for Review Figure shows photographs of individuals suffering from various endocrine disorders.

115 Principles of Human Anatomy and Physiology, 11e115 Adrenal Cortex - Review Mineralocorticoids –Mineralocorticoids (e.g., aldosterone) increase sodium and water reabsorption and decrease potassium reabsorption, helping to regulate sodium and potassium levels in the body. –Secretion is controlled by the renin-angiotensin pathway (Figure 18.16) and the blood level of potassium. Glucocorticoids –Glucocorticoids (e.g., cortisol) promote breakdown of proteins, formation of glucose, lipolysis, resistance to stress, anti-inflammatory effects, and depression of the immune response. –Secretion is controlled by CRH (corticotropin releasing hormone) and ACTH (adrenocorticotropic hormone) from the anterior pituitary (Figure 18.17). Androgens –Androgens secreted by the adrenal cortex usually have minimal effects.

116 Principles of Human Anatomy and Physiology, 11e116 Adrenal Medulla - Review The adrenal medulla consists of hormone-producing cells, called chromaffin cells, which surround large blood-filled sinuses. Medullary secretions are epinephrine and norepinephrine (NE), which produce effects similar to sympathetic responses. They are released under stress by direct innervation from the autonomic nervous system. Like the glucocorticoids of the adrenal cortex, these hormones help the body resist stress. However, unlike the cortical hormones, the medullary hormones are not essential for life. Table 18.8 summarizes the hormones produced by the adrenal glands, the principal actions, and control of secretion.

117 Principles of Human Anatomy and Physiology, 11e117 Review: Cell Types in the Pancreatic Islets Alpha cells secrete the hormone glucagon which increases blood glucose levels. Beta cells secrete the hormone insulin which decreases blood glucose levels. Delta cells secrete growth hormone inhibiting hormone or somatostatin, which acts as a paracrine to inhibit the secretion of insulin and glucagon. F-cells secrete pancreatic polypeptide, which regulates release of pancreatic digestive enzymes.

118 Principles of Human Anatomy and Physiology, 11e118 OVARIES AND TESTES - Review Ovaries are located in the pelvic cavity and produce sex hormones (estrogens and progesterone) related to development and maintenance of female sexual characteristics, reproductive cycle, pregnancy, lactation, and normal reproductive functions. The ovaries also produce inhibin and relaxin. Testes lie inside the scrotum and produce sex hormones (primarily testosterone) related to the development and maintenance of male sexual characteristics and normal reproductive functions. The testes also produce inhibin.

119 Principles of Human Anatomy and Physiology, 11e119 PINEAL GLAND - Review The pineal gland (epiphysis cerebri) is attached to the roof of the third ventricle, inside the brain (Figure 18.1). Histologically, it consists of secretory parenchymal cells called pinealocytes, neuroglia cells, and scattered postganglionic sympathetic fibers. The pineal secrets melatonin in a diurnal rhythm linked to the dark-light cycle. Seasonal affective disorder (SAD), a type of depression that arises during the winter months when day length is short, is thought to be due, in part, to over-production of melatonin. Bright light therapy, repeated doses of several hours exposure to artificial light as bright as sunlight, may provide relief for this disorder and for jet lag.

120 Principles of Human Anatomy and Physiology, 11e120 THYMUS GLAND The thymus gland secretes several hormones related to immunity. Thymosin, thymic humoral-factor, thymic factor, and thymopoietin promote the proliferation and maturation of T cells, a type of white blood cell involved in immunity.


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