BIOLOGY. 1. Overview of Endrocrine Hormone Signaling 10/22/2014. Hormones and the Endocrine System. The Body s Long-Distance Regulators

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CAMPBELL BIOLOGY TENTH EDITION 45 Reece Urry Cain Wasserman Minorsky Jackson Hormones and the Endocrine System Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick 1. Overview of Endrocrine Hormone Signaling The Body s Long-Distance Regulators Animal hormones are chemical signals that are secreted into the circulatory system and communicate regulatory messages within the body Hormones reach all parts of the body, but only target cells have receptors for that hormone 1

Intercellular Communication The ways that signals are transmitted between animal cells are classified by two criteria The type of secreting cell The route taken by the signal in reaching its target Paracrine and Autocrine Signaling Local regulators are molecules that act over short distances, reaching target cells solely by diffusion In paracrine signaling, the target cells lie near the secreting cells In autocrine signaling, the target cell is also the secreting cell Figure 45.2a Blood vessel RESPONSE (a) Endocrine signaling RESPONSE (b) Paracrine signaling RESPONSE (c) Autocrine signaling 2

Paracrine and autocrine signaling play roles in processes such as blood pressure regulation, nervous system function, and reproduction Local regulators that mediate such signaling include the prostaglandins Prostaglandins function in reproduction, the immune system, and blood clotting Synaptic and Neuroendocrine Signaling In synaptic signaling, neurons form specialized junctions with target cells, called synapses At synapses, neurons secrete molecules called neurotransmitters that diffuse short distances and bind to receptors on target cells In neuroendocrine signaling, specialized neurosecretory cells secrete molecules called neurohormones that travel to target cells via the bloodstream Figure 45.2b Neuron Synapse (d) Synaptic signaling Neurosecretory cell RESPONSE Blood vessel RESPONSE (e) Neuroendocrine signaling 3

Signaling by Pheromones Members of an animal species sometimes communicate with pheromones, chemicals that are released into the environment Pheromones serve many functions, including marking trails leading to food, defining territories, warning of predators, and attracting potential mates Classes of Local Regulators Local regulators such as the prostaglandins are modified fatty acids Others are polypeptides and some are gases Nitric oxide (NO) is a gas that functions in the body as both a local regulator and a neurotransmitter When the level of oxygen in blood falls, NO activates an enzyme that results in vasodilation, increasing blood flow to tissues Hormones fall into three major classes: polypeptides, steroids, and amines Classes of Hormones Water-soluble (hydrophilic) Lipid-soluble (hydrophobic) Polypeptides Steroids Polypeptides and amines are watersoluble whereas steroid hormones and other largely nonpolar hormones are lipid-soluble 0.8 nm Insulin Amines Epinephrine Cortisol Thyroxine 4

Cellular Response Pathways Water-soluble hormones are secreted by exocytosis, travel freely in the bloodstream, and bind to cell-surface receptors Lipid-soluble hormones diffuse across cell membranes, travel in the bloodstream bound to transport proteins, and diffuse through the membrane of target cells They bind to receptors in the cytoplasm or nucleus of the target cells Figure 45.5 (a) Water-soluble hormone; receptor in plasma membrane SECRETORY CELL (b) Lipid-soluble hormone; receptor in nucleus or cytoplasm SECRETORY CELL Watersoluble hormone Lipidsoluble hormone Blood vessel Receptor protein TARGET OR CELL Blood vessel Transport protein TARGET CELL Receptor protein Cytoplasmic Gene response regulation NUCLEUS Cytoplasmic response Gene regulation NUCLEUS Water-Soluble Hormones require Signal Transduction For example: The hormone epinephrine has multiple effects in mediating the body s response to short-term stress Epinephrine binds to receptors on the plasma membrane of liver cells This triggers the release of messenger molecules that activate enzymes and result in the release of glucose into the bloodstream 5

Figure 45.6 An Example of Signal Transduction EXTRACELLULAR FLUID Hormone (epinephrine) G protein Adenylyl cyclase G protein-coupled receptor GTP Inhibition of glycogen synthesis Promotion of glycogen breakdown ATP camp Second messenger Protein kinase A CYTOPLASM Signaling with Lipid-Soluble Hormones When a steroid hormone binds to its cytosolic receptor, a hormone-receptor complex forms that moves into the nucleus There, the receptor part of the complex acts as a transcriptional regulator of specific target genes Estradiol receptor NUCLEUS Hormone (estradiol) mrna for vitellogenin DNA EXTRACELLULAR FLUID Plasma membrane Hormone-receptor complex CYTOPLASM Vitellogenin Multiple Effects of Hormones The same hormone may have different effects on target cells that have Different receptors for the hormone Different signal transduction pathways For example, the hormone epinephrine can increase blood flow to major skeletal muscles, but decrease blood flow to the digestive tract 6

Negative feedback 10/22/2014 Figure 45.8 Same receptors but different intracellular proteins (not shown) Different receptors (a) Liver cell Epinephrine β receptor Glycogen deposits (b) Smooth muscle cell in wall of blood vessel that supplies skeletal muscle Epinephrine β receptor (c) Smooth muscle cell in wall of blood vessel that supplies intestines Epinephrine α receptor Glucose Glycogen breaks down and glucose is released from cell. Blood glucose level increases. Cell relaxes. Blood vessel dilates, increasing flow to skeletal muscle. Cell contracts. Blood vessel constricts, decreasing flow to intestines. Feedback Regulation A negative feedback loop inhibits a response by reducing the initial stimulus, thus preventing excessive pathway activity For example, the release of acidic contents of the stomach into the duodenum stimulates endocrine cells there to secrete secretin This causes target cells in the pancreas, a gland behind the stomach, to raise the ph in the duodenum Figure 45.10 Simple endocrine pathway STIMULUS Endocrine cell Example: secretin signaling Low ph in duodenum S cells of duodenum Hormone Secretin ( ) Target cells Pancreatic cells RESPONSE Bicarbonate release 7

Positive feedback 10/22/2014 Positive feedback reinforces a stimulus to produce an even greater response For example, in mammals oxytocin causes the release of milk, causing greater suckling by offspring, which stimulates the release of more oxytocin Figure 45.11 Simple neuroendocrine pathway STIMULUS Example: oxytocin signaling Suckling Hypothalamus/ posterior pituitary Sensory neuron Neurosecretory cell Neurohormone Oxytocin ( ) Target cells Smooth muscle in mammary glands RESPONSE Milk release Endocrine Tissues and Organs Endocrine cells are often grouped in ductless organs called endocrine glands, such as the thyroid and parathyroid glands, testes, and ovaries In contrast, exocrine glands, such as salivary glands have ducts to carry secreted substances onto body surfaces or into body cavities 8

Figure 45.9 2. Coordination of the Endocrine and Nervous Systems Invertebrates The endocrine pathway that controls the molting of larva originates in the larval brain where neurosecretory cells produce PTTH In the prothoracic gland, PTTH directs the release of ecdysteroid Bursts of ecdysteroid trigger each successive molt as well as metamorphosis Metamorphosis is not triggered until the level of another hormone, JH (juvenile hormone), drops 9

Figure 45.12-4 Prothoracic gland PTTH Brain Neurosecretory cells Corpora cardiaca Corpora allata High JH Ecdysteroid Low JH EARLY LARVA LATER LARVA PUPA ADULT Vertebrates The hypothalamus receives information from the nervous system and initiates responses through the endocrine system Attached to the hypothalamus is the pituitary gland, composed of the posterior pituitary and anterior pituitary The posterior pituitary stores and secretes hormones that are made in the hypothalamus The anterior pituitary makes and releases hormones under regulation of the hypothalamus Figure 45.13 Pineal gland Cerebellum Spinal cord Cerebrum Thalamus Hypothalamus Pituitary gland Posterior pituitary Hypothalamus Anterior pituitary 10

Posterior Pituitary Hormones Neurosecretory cells of the hypothalamus synthesize the two posterior pituitary hormones Antidiuretic hormone (ADH) regulates physiology and behavior Oxytocin regulates milk secretion by the mammary glands Figure 45.14 Hypothalamus Neurosecretory cells of the hypothalamus Neurohormone Axons Posterior pituitary Anterior pituitary HORMONE ADH Oxytocin TARGET Kidney tubules Mammary glands, uterine muscles Anterior Pituitary Hormones Hormone production in the anterior pituitary is controlled by releasing hormones and inhibiting hormones secreted by the hypothalamus For example, prolactin-releasing hormone from the hypothalamus stimulates the anterior pituitary to secrete prolactin (PRL), which has a role in milk production 11

Figure 45.15 Neurosecretory cells of the hypothalamus HORMONE TARGET Hypothalamic releasing and inhibiting hormones Posterior pituitary Portal vessels Endocrine cells of the anterior pituitary Anterior pituitary hormones FSH and LH TSH ACTH Prolactin MSH GH Testes or ovaries Thyroid Adrenal cortex Mammary glands Melanocytes Liver, bones, other tissues Tropic effects only Nontropic effects only Tropic and nontropic effects Hormone Cascades Sets of hormones from the hypothalamus, anterior pituitary, and a target endocrine gland are often organized into a hormone cascade pathway The anterior pituitary hormones in these pathways are called tropic hormones hormones that target other endocrine glands Non-tropic hormones stimulate targets other than endocrine glands Thyroid Regulation: A Hormone Cascade Pathway In humans and other mammals, thyroid hormone regulates many functions If thyroid hormone level drops in the blood, the hypothalamus secretes thyrotropin-releasing hormone (TRH) causing the anterior pituitary to secrete thyroid-stimulating hormone (TSH) TSH stimulates release of thyroid hormone by the thyroid gland 12

End product of cascade, thyroid hormone, creates negative feedback. 10/22/2014 Figure 45.16a STIMULUS Sensory neuron Hypothalamus Neurosecretory cell TRH 1 Thyroid hormone levels drop. 2 The hypothalamus secretes TRH into the blood. Portal vessels carry TRH to anterior pituitary. TSH 3 TRH causes anterior pituitary to secrete TSH. Anterior pituitary Figure 45.16b TSH TSH circulation throughout body via blood 6 Thyroid hormone blocks TRH release and TSH release preventing overproduction of thyroid hormone. RESPONSE Thyroid gland Thyroid hormone 4 Circulation throughout body via blood 5 TSH stimulates endocrine cells in thyroid gland to secrete T 3 and T 4. Thyroid hormone levels return to normal range. Disorders of Thyroid Function and Regulation Hypothyroidism, too little thyroid function, can produce symptoms such as Weight gain, lethargy, cold intolerance Hyperthyroidism, excessive production of thyroid hormone, can lead to High temperature, sweating, weight loss, irritability, and high blood pressure Malnutrition can alter thyroid function 13

Graves disease, a form of hyperthyroidism caused by autoimmunity, is typified by protruding eyes Thyroid hormone refers to a pair of hormones Triiodothyronin (T 3 ), with three iodine atoms Thyroxine (T 4 ), with four iodine atoms Insufficient dietary iodine leads to an enlarged thyroid gland, called a goiter Hormonal Regulation of Growth Growth hormone (GH) is secreted by the anterior pituitary gland and has tropic and nontropic effects It promotes growth directly and has diverse metabolic effects It stimulates production of growth factors An excess of GH can cause gigantism, while a lack of GH can cause dwarfism 3. Other Endocrine Hormones 14

Parathyroid Hormone and Vitamin D: Control of Blood Calcium Two antagonistic hormones regulate the homeostasis of calcium (Ca 2+ ) in the blood of mammals Parathyroid hormone (PTH) is released by the parathyroid glands Calcitonin is released by the thyroid gland Figure 45.19 Blood Ca 2+ level rises. NORMAL BLOOD Ca 2+ LEVEL (about 10 mg/100 ml) Active vitamin D increases Ca 2+. Blood Ca 2+ level falls. PTH stimulates Ca 2+ uptake and promotes activation of vitamin D. PTH stimulates Ca 2+ release. PTH Parathyroid glands release PTH. PTH increases the level of blood Ca 2+ It releases Ca 2+ from bone and stimulates reabsorption of Ca 2+ in the kidneys It also has an indirect effect, stimulating the kidneys to activate vitamin D, which promotes intestinal uptake of Ca 2+ from food Calcitonin decreases the level of blood Ca 2+ It stimulates Ca 2+ deposition in bones and secretion by kidneys 15

Adrenal Hormones: Response to Stress The adrenal glands are associated with the kidneys Each adrenal gland actually consists of two glands: the adrenal medulla (inner portion) and adrenal cortex (outer portion) Catecholamines from the Adrenal Medulla The adrenal medulla secretes epinephrine (adrenaline) and norepinephrine (noradrenaline) These hormones are members of a class of compounds called catecholamines They are secreted in response to stress-activated impulses from the nervous system Figure 45.20a (a) Short-term stress response (b) Long-term stress response Nerve Spinal impulses cord (cross section) Adrenal medulla Neuron Neuron Stress Releasing hormone ACTH Hypothalamus Anterior pituitary Blood vessel Secretion of epinephrine and norepinephrine Adrenal gland Kidney Adrenal cortex Secretion of mineraloand glucocorticoids 16

Epinephrine and Norepinephrine Trigger the release of glucose and fatty acids into the blood Increase oxygen delivery to body cells Direct blood toward heart, brain, and skeletal muscles and away from skin, digestive system, and kidneys (a) Short-term stress response and the adrenal medulla Effects of epinephrine and norepinephrine: Glycogen broken down to glucose; increased blood glucose Increased blood pressure Increased breathing rate Increased metabolic rate Change in blood flow patterns, leading to increased alertness and decreased digestive, excretory, and reproductive system activity Steroid Hormones from the Adrenal Cortex The adrenal cortex reacts to endocrine signals It releases a family of steroids called corticosteroids in response to stress These hormones are triggered by a hormone cascade pathway via the hypothalamus and anterior pituitary Humans produce two types of corticosteroids: glucocorticoids and mineralocorticoids Figure 45.20c Glucocorticoids, such as cortisol, influence glucose metabolism and the immune system Mineralocorticoids, such as aldosterone, affect salt and water balance (b) Long-term stress response and the adrenal cortex Effects of mineralocorticoids: Retention of sodium ions and water by kidneys Increased blood volume and blood pressure Effects of glucocorticoids: Proteins and fats broken down and converted to glucose, leading to increased blood glucose Partial suppression of immune system 17

Sex Hormones The gonads, testes and ovaries, produce most of the sex hormones: androgens, estrogens, and progestins All three sex hormones are found in both males and females, but in significantly different proportions Androgens The testes primarily synthesize androgens, mainly testosterone, which stimulate development and maintenance of the male reproductive system Testosterone causes an increase in muscle and bone mass and is often taken as a supplement to cause muscle growth, which carries health risks Estrogens & Progestins Estrogens, most importantly estradiol, are responsible for maintenance of the female reproductive system and the development of female secondary sex characteristics In mammals, progestins, which include progesterone, are primarily involved in preparing and maintaining the uterus Synthesis of the sex hormones is controlled by follicle-stimulating hormone and luteinizing hormone from the anterior pituitary Figure 45.21 Bipotential gonad Male duct (Wolffian) Female duct (Müllerian) Testosterone Embryo (XY or XX) AMH Absence of male hormones Testis Ovary Vas deferens Seminal vesicle Bladder Uterus Bladder Oviduct Male (XY) fetus Female (XX) fetus 18

Hormones and Biological Rhythms The pineal gland, located in the brain, secretes melatonin Primary functions of melatonin appear to relate to biological rhythms associated with reproduction and with daily activity levels The release of melatonin by the pineal gland is controlled by a group of neurons in the hypothalamus called the suprachiasmatic nucleus (SCN) 19