Ch. 16 Lecture Outline PDF

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Ch. 16 Lecture Outline...

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CHAPTER 16: THE ENDOCRINE SYSTEM THE ENDOCRINE SYSTEM: AN OVERVIEW Endocrine system: The endocrine system functions to control/regulate cellular metabolism via hormones. Hormones are released from endocrine glands and various other structures and bind to specific cellular receptors on target cells. After the hormone binds to its receptor, a cellular response begins, which alters cellular metabolism until deactivation of the receptor-hormone complex occurs. For a brief animated explanation of the endocrine system, please view: Overview of the Endocrine System. Hormones: Hormones are chemicals (molecules) secreted by endocrine glands or other structures directly into the blood supply, and they function to trigger signals in specific target cells. These chemicals cause a variety of effects in the body, but the major processes they control are reproduction; growth; development; maintain water, nutrient, and electrolyte homeostasis; regulate cellular metabolism and energy balance; and mobilize body defenses. Endocrine glands: Endocrine glands are ductless glands that function to synthesize and secrete hormones. They release hormones into the interstitial fluid surrounding blood capillaries. After entering the interstitial fluid, the hormones will diffuse across capillary walls into the blood. Examples: pituitary gland; thyroid gland; pineal gland; adrenal glands Neuroendocrine glands: Neuroendocrine glands are hormone-secreting structures located in the brain. Example: hypothalamus Hormone-secreting tissues and organs: Various hormone-secreting structures are located in the body. Examples: heart; pancreas; stomach; small intestine; gonads; adipose tissue; placenta Autocrines: Autocrines are molecules that affect the structures that secrete them. Example: Smooth muscle cells secrete prostaglandins, which cause smooth muscle cells to contract. Paracrines: Paracrines are molecules that affect structures that surround those that secrete them. Example: Somatostatin is secreted by one group of pancreatic cells and functions to inhibit the secretion of insulin from another group of pancreatic cells ( cells). BASIC HORMONE TYPES Amino-acid based hormones: Most hormones are amino-acid based hormones, which are water-soluble These hormones exhibit various molecular sizes from small peptides to large proteins. Steroids: Steroid hormones are lipid-soluble and are synthesized from cholesterol. Examples: gonadal hormones (i.e. estrogens; progesterone; testosterone); adrenocortical hormones (i.e. cortisol) Eicosanoids: Eicosanoids are biologically active lipids that are secreted from most cell membranes, and they include leukotrienes and prostaglandins. Leukotrienes: These are signaling chemicals involved in allergic and inflammatory reactions. Prostaglandins: These are signaling chemicals involved in inflammatory reactions, blood coagulation, increasing blood pressure, increasing uterine contractions during childbirth, and enhancing the sensation of pain. TARGET CELLS, HORMONE RECEPTORS, AND HORMONE ACTION Target cells: Target cells are specific tissue cells that respond to hormones. Hormones alter target-cell activity by increasing or decreasing cellular metabolic rates. Hormonal stimulus can cause the following actions of target cells: 

Alters cell (plasma) membrane permeability, membrane potential, or both by opening/closing ion channels Page 1

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CHAPTER 16: THE ENDOCRINE SYSTEM Stimulates synthesis of proteins or regulatory molecules Activates or deactivates enzymes Induces secretory activity Stimulates mitosis

Target-cell specificity: In order for a hormone to bind to a target cell, the cell must have specific extracellular or intracellular receptors that allow the hormone to bind it. Target-cell receptors have specific binding sites that bond to hormones forming hormone-receptor complexes. When the hormone-receptor complex forms, it causes a signaling cascade, which changes activity of the target cell. Target-cell activation via hormone-receptor interaction depends on the following factors:   

Blood levels of the hormone Number of receptors for the hormone on or in the target cell Affinity of binding between the hormone and receptor

Hormone receptors: Hormone receptors are dynamic as they respond to the hormone concentration in the blood. Up-regulation of receptors: Up-regulation of receptors involves target cells synthesizing more receptors in response to rising blood levels of specific hormones. Down-regulation of receptors: Down-regulation of receptors involves target cells becoming desensitized to prolonged periods of high-hormone concentration, so hormone receptors are catabolized to prevent the cell from overreacting to high-hormone levels. Hormone interactions at target cells: Hormone interaction is unpredictable because multiple hormones can act on the same target cell causing very different effects than those caused by each individual hormone alone. Permissiveness: Permissiveness involves one hormone requiring another hormone to exert its full effects. Example: The presence of thyroid hormone is necessary to allow reproductive structures to develop. Synergism: Synergism involves multiple hormones acting on the same target cell, and when they act together, their effects are amplified. Example: Glucagon and epinephrine act together to cause the release of 150% more glucose from hepatocytes (liver cells) and skeletal muscle cells as compared to when they act alone. Antagonism: Antagonism involves one hormone opposing the action of another hormone. Antagonists compete for the same receptor but act through different metabolic pathways. Example: Insulin functions to lower blood-glucose levels by enhancing membrane transport of glucose into body cells, and glucagon functions to raise blood-glucose levels by enhancing the release of glucose into the blood from hepatocytes. Receptor-mediated action of hormones: In order for hormones to cause an effect on target cells, they must bind to intracellular or extracellular receptors. After binding occurs, a signaling cascade begins increasing or decreasing cellular metabolism. Water-soluble hormones: All amino-acid based hormones are water-soluble, except thyroid hormone. These hormones act on the extracellular surface of cell-membrane receptors. After the hormone binds to its receptor, the receptor will activate causing a signaling cascade to occur. The activated hormone-receptor complex causes activation of a G protein and several other enzymes, which alters the cell’s metabolism. For a brief animated explanation of the action of water-soluble hormones, please view: Water Soluble Hormones and Intracellular Signaling. Plasma-membrane receptors and second-messenger systems:

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CHAPTER 16: THE ENDOCRINE SYSTEM Cyclic AMP signaling mechanism: This signaling mechanism is initiated by the binding of a water-soluble hormone to the extracellular receptor surface and involves the interaction of three cell-membrane components, which determines the intracellular levels of cAMP (second messenger).

1. Hormone (first messenger) binds to receptor Binding of hormone causes a conformational change of the receptor, which activates the receptor. 2. Receptor activates G-protein The activated receptor binds to a G-protein, which is located on the intracellular surface of the cell membrane. When this occurs, the G-protein “turns on” or activates when GDP is displaced by GTP. 3. G-protein activates adenylate cyclase The activated G-protein moves along the intracellular cell-membrane surface and binds to adenylate cyclase (transmembrane protein). Binding of the G-protein to adenylate cyclase will either stimulate or inhibit adenylate cyclase. Eventually, the G-protein will inactivate as GTP is hydrolyzed to GDP. 4. Adenylate cyclase converts ATP to cyclic AMP (second messenger) Activated adenylate cyclase causes ATP to convert to cyclic AMP (cAMP) 5. Cyclic AMP activates protein kinases Page 3

CHAPTER 16: THE ENDOCRINE SYSTEM cAMP diffuses throughout the cell triggering a cascade of biochemical reactions by activating protein kinases (enzymes that phosphorylate various proteins). Phosphorylation (adding a phosphate group to proteins) will activate or inhibit proteins causing a various cellular responses within the target cell. **cAMP molecules and one protein kinase enzyme can catalyze hundreds of reactions, causing the reaction cascade to synthesize many molecules at each step of the reaction. Thus, hormone activation of a receptor causes an amplification effect, where millions of product molecules are generated from the reaction!** Lipid-soluble hormones: All steroid hormones are lipid-soluble. These hormones diffuse into their target cells, where they bind to and activate intracellular receptors. The activated hormone-receptor complex enters the nucleus, where it binds to a region of DNA called a hormone response element. This interaction causes gene expression to begin (transcription and translation), which results in the synthesis of specific proteins in the target cell. For a brief animated explanation of the action of lipid-soluble hormones, please view: Action of Steroid Hormones.

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CHAPTER 16: THE ENDOCRINE SYSTEM Intracellular receptors and direct gene activation: 1. Steroid hormone diffuses into target cell and binds to an intracellular receptor 2. Activated receptor-hormone complex enters the nucleus via the nuclear pores

3. Activated receptor-hormone complex binds to a specific region of DNA (hormone response element) located on the chromatin 4. Binding of receptor-hormone complex to hormone response element initiates transcription process of the gene to form mRNA 5. mRNA strand exits the nucleus to begin translation of the protein in the cytoplasm Control of hormone release from endocrine glands: The synthesis and release of hormones are regulated by specific stimuli and negative feedback systems. Humoral stimuli: Some hormones are secreted in response to humoral stimuli, which are blood levels of specific ions and nutrients. Example: When calcium-ion levels in the blood decrease, the parathyroid glands respond by secreting parathyroid hormone (PTH). PTH acts on osteoclasts causing them to increase catabolism of bone matrix to release calcium ions into the blood. Neural stimuli: Some hormones are secreted in response to nerve-fiber stimulation. Example: Sympathetic nervous system stimulates the adrenal medulla to release epinephrine. Hormonal stimuli: Some hormones are secreted in response to the release of other hormones. Example: Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus, and it acts on the anterior pituitary to cause the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH act on the ovaries to cause the release of estrogen and act on the testes to cause the release of testosterone.

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CHAPTER 16: THE ENDOCRINE SYSTEM SPECIFIC HORMONE-SECRETING STRUCTURES Pituitary gland (hypophysis): Pituitary gland is about the size of a pea, and it connects superiorly to the hypothalamus via its infundibulum. It’s composed of two lobes: anterior pituitary and posterior pituitary. Anterior pituitary (adenohypophysis): This lobe of the pituitary gland is composed of glandular tissue, and it synthesizes and secretes many hormones.

Growth hormone (GH or somatotropin): GH functions as an anabolic hormone. GH actions:  Promotes protein synthesis  Utilizes fats for energy by increasing blood levels of fatty acids and transporting fat to cells  Conserves glucose by decreasing the rate of glucose uptake and metabolism  Encourages glycogen catabolism in the liver and the release of glucose into the blood Thyroid-stimulating hormone (TSH or thyrotropin): TSH functions to stimulate the normal development and secretory activity of the thyroid gland. Adrenocorticotropic hormone (ACTH or corticotropin): ACTH functions to stimulate the adrenal cortex to release corticosteroid hormones, like glucocorticoids to help the body resist stressors. Gonadotropins: Gonadotropins regulate the function of the gonads (ovaries and testes). Follicle-stimulating hormone (FSH): FSH functions to stimulate gamete (egg and sperm) production. Luteinizing hormone (LH): LH functions to promote production of the gonadal hormones (estrogens and testosterone). Prolactin (PRL): PRL functions to stimulate milk production by the breasts. Posterior pituitary (neurohypophysis): This lobe of the pituitary gland is mainly composed of axons of hypothalamic neurons. Page 6

CHAPTER 16: THE ENDOCRINE SYSTEM

Oxytocin: Oxytocin functions to stimulate smooth muscle fibers of the uterus causing contractions during childbirth, and it triggers milk ejection in women producing milk due to prolactin release. Antidiuretic hormone (ADH or vasopressin): ADH functions to maintain water balance by helping the body avoid dehydration and water overload. Hypothalamus: The hypothalamus is located inferior to the thalamus in the brain. It’s connected to the pituitary gland and composed of several nuclei. Gonadotropin-releasing hormone (GnRH): GnRH functions to cause the release of the FSH and LH (gonadotropins). Thyroid gland: This is a bowtie-shaped or butterfly-shaped gland located anteriorly in the neck region, inferior to the larynx. It’s composed of two lobes that are connected by a tissue mass called the isthmus, and it’s the largest pure endocrine gland in the body!

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CHAPTER 16: THE ENDOCRINE SYSTEM Thyroid hormone (TH): TH is considered the body’s major metabolic hormone, and it’s actually two hormones: T 4 and T3. TH actions:  Increases basal metabolic rate and body heat production via glucose oxidation (calorigenic effect)  Plays a role in maintaining blood pressure by increasing the number of adrenergic receptors in blood vessels  Regulates tissue growth and development T4 (thyroxine): T4 is the major hormone secreted by the thyroid gland. T3 (triiodothyronine): T3 is formed at the target tissues via conversion of T4 to T3. Calcitonin: Calcitonin functions to lower blood-calcium levels by antagonizing the effects of parathyroid hormone. It targets bone tissue by inhibiting osteoclast activity and stimulates calcium ion uptake and incorporation into the bone matrix. Parathyroid glands: These tiny glands are located on the posterior side of the thyroid gland. Typically, there are four of them, but the number varies in each person.

Parathyroid hormone (PTH): PTH functions to increase calcium-ion levels in the blood by acting on bone tissue, kidneys, and the intestines. Adrenal glands: These two, pyramid-shaped glands are located superior to the kidneys, and they are composed of an inner adrenal medulla and an outer adrenal cortex. Adrenal cortex: The adrenal cortex is the outer region of the adrenal glands, and it’s composed of glandular tissue. The adrenal cortex functions to synthesize and secrete corticosteroids (steroid hormones). Mineralocorticoids: These hormones function to regulate electrolyte concentrations in extracellular fluids, specifically sodium- ion and potassium-ion concentrations. Aldosterone is the most abundant mineralocorticoid, which functions to reduce sodium-ion excretion by stimulating sodium-ion reabsorption in the kidney tubules and enhances sodium-ion reabsorption from perspiration, saliva, and gastric juice. Aldosterone, also, helps retain water, eliminates potassium ions from the body, and alters the acid-base homeostasis of the blood.

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CHAPTER 16: THE ENDOCRINE SYSTEM Glucocorticoids: These hormones are involved in cellular energy metabolism and help the body resist stressors by keeping blood-glucose levels constant and by maintaining blood pressure. Glucocorticoids include cortisol (hydrocortisone), cortisone, and corticosterone. Gonadocorticoids (sex hormones): These hormones are believed to cause the onset of puberty in males and females and cause a variety of secondary sexual characteristics to form and development. Adrenal medulla: The adrenal medulla is the inner region of the adrenal glands, and it’s composed of nervous tissue. Its hormones are involved in responses of the sympathetic nervous system. Epinephrine: Epinephrine functions to stimulate metabolic activities, dilate bronchioles, and increase blood flow to skeletal and cardiac muscle. Norepinephrine: Norepinephrine functions in peripheral vasoconstriction and blood pressure.

Pineal gland: The pineal gland is located superior to the thalamus near the third ventricle in the brain. Melatonin: Melatonin functions to induce sleep and mediates circadian rhythms and influences physiological processes that show rhythmic variations (i.e. body temperature, sleep, and appetite). Pancreas: The pancreas is located posterior to the stomach and is an exocrine and endocrine gland. Glucagon: Glucagon actions:  Catabolism of glycogen to glucose (glycogenolysis) Page 9

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CHAPTER 16: THE ENDOCRINE SYSTEM Synthesis of glucose from lactic acid and from noncarbohydrate molecules (gluconeogenesis) Release of glucose into the blood via hepatocytes (liver cells) causing an increase in blood-glucose levels

Insulin: Insulin actions:  Lowers blood-glucose levels by enhancing membrane transport of glucose into body cells, especially muscle and fat cells  Inhibits catabolism of glycogen to glucose  Inhibits conversion of amino acids and fats to glucose Ovaries: The paired ovaries are located lateral to the uterus and Fallopian tubes in the female’s abdominopelvic cavity. Estrogens: Estrogens function in the maturation of female reproductive organs and the appearance of secondary sexual characteristics at puberty. Progesterone: Acting with estrogens, progesterone functions to promote breast development and regulates cyclic changes during the menstrual cycle. Testes: The paired testes are located in the scrotum lateral to the penis. Testosterone: Testosterone functions in the maturation of male reproductive organs, the appearance of secondary sexual characteristics at puberty, and promotes sex drive.

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