Chapter 17 Endocrine System PDF

chapter Endocrine System INTEGRATE 17.1 Introduction to the...

chapter Endocrine System INTEGRATE 17.1 Introduction to the Endocrine System 17 17.7b Interactions Between the Hypothalamus and the Posterior Pituitary Gland 17.1a Overview of the Endocrine System 17.7c Interactions Between the 17.1b Comparison of the Two Control Hypothalamus and the Anterior Systems Pituitary Gland 17.1c General Functions of the Endocrine 17.7d Growth Hormone: Its Regulation System and Effects 17.2 Endocrine Glands 17.8 Thyroid Gland 17.2a Location of the Major Endocrine 17.8a Anatomy of the Thyroid Gland Glands 17.8b Thyroid Hormone: Its Regulation 17.2b Stimulation of Hormone Synthesis and Effects and Release 17.8c Calcitonin: Its Regulation and Effects 17.3 Categories of Hormones 17.9 Adrenal Glands 17.3a Circulating Hormones 17.9a Anatomy of the Adrenal Glands 17.3b Local Hormones 17.9b Cortisol: Its Regulation and Effects 17.4 Hormone Transport 17.10 The Pancreas 17.4a Transport in the Blood 17.10a Anatomy of the Pancreas 17.4b Levels of Circulating Hormone 17.10b Pancreatic Hormones 17.5 T  arget Cells: Interactions 17.11 Other Endocrine Glands with Hormones 17.11a Pineal Gland 17.5a Lipid-Soluble Hormones 17.11b Parathyroid Glands ©Lea Paterson/Science Source 17.5b Water-Soluble Hormones 17.11c Structures with an Endocrine 17.6 T  arget Cells: Degree of Function CAREER PATH Cellular Response 17.12 Aging and the Endocrine Endocrinologist 17.6a Number of Receptors on a Target Cell System An endocrinologist is a physician who special- 17.6b Hormone Interactions on a Target Cell Major Regulatory Hormones izes in the treatment of endocrine disorders. The 17.7 T  he Hypothalamus and of the Human Body thyroid gland is the most commonly treated endo- the Pituitary Gland crine gland. This gland is located on the anterior 17.7a Anatomic Relationship of the side of the neck. It produces and releases thyroid Hypothalamus and the Pituitary Gland hormone to regulate and control metabolism. INTEGRATE: Concept Overview Palpation of a physical anomaly of the thyroid Endocrine System: Major Control System gland is often the first indication of a thyroid of the Body Module 8: Endocrine System gland disorder (e.g., goiter, Graves disease). Some days are just more hectic than others. We don’t have time for This chapter has two primary purposes. The first is to provide an breakfast and then perhaps have a class that meets over the lunch hour, introduction and general discussion of the endocrine system’s central allowing us only enough time to grab something from the snack concepts, including endocrine glands, categories of hormones, hormone machine before heading off to work or other classes in the afternoon. transport in the blood, and how hormones interact with body cells. The Finally, upon returning home for the evening, we are so hungry we eat second is to present the general function of the major hormones of the rapidly and have a second helping. Fortunately, our endocrine system body and the detailed processes by which selected representative has come to our rescue, maintaining blood glucose levels within normal hormones maintain body homeostasis. The final section of this chapter homeostatic limits during this period of erratic food intake. Through the describes the effects of aging on the endocrine system. Please note release of hormones, the endocrine system provides the means to that each major hormone described in this text can be quickly accessed regulate and control many diverse metabolic processes of the body, in the summary tables provided in the reference section immediately including regulating blood sugar. after this chapter (designated R1–R10). 653  17.1a Overview of the Endocrine System 17.1 Introduction to LEARNING OBJECTIVE the Endocrine System 1. Describe the general features of the endocrine system, including The endocrine system serves as one of the two major control systems how hormones are transported between an endocrine gland and its that regulate the human body; the other is the nervous system, which target cells. was described in the preceding chapters. Here we provide an over- view of how this system of control functions, compare its means of The endocrine system is composed of endocrine glands located controlling the body to that of the nervous system, and then preview throughout the body. These glands synthesize and secrete molecules the general functions of the endocrine system. called hormones (hormao = to rouse) that communicate with and control other body cells. This communication is possible because body cells display various cellular receptors for specific types of hormones (e.g., skeletal muscle cells have receptors for testosterone, osteoblasts of bone have receptors for parathyroid hormone). Cells that have specific receptors for a hormone are called target cells. Each type of hormone differs in its target cells and thus, the cellular Interstitial Target activities that it regulates. fluid cell How is it possible for endocrine glands to synthesize and secrete Capillary hormones that control cells, which are often located significant dis- tances from the gland? The hormone molecules are transported from Heart the endocrine gland to the target cells by the blood. This process occurs as follows (figure 17.1): Vein Artery 1. Endocrine glands lack ducts (unlike exocrine glands, which release their secretions into ducts; see section 5.1d). Hormone molecules are instead released from endocrine (b) Cardiovascular gland cells into the interstitial fluid and then enter the blood system within capillaries (figure 17.1a). (c) Target organ 2. These hormone molecules are transported within the blood from the endocrine gland’s associated capillaries by the cardiovascular system to all body tissues (figure 17.1b), a process that is relatively slow (in comparison to the nervous system). 3. The hormones randomly leave the blood from the capillaries and enter the interstitial fluid, which provides the hormone molecules access to potentially all body cells (figure 17.1c). Neuron Consequently, the response induced by each hormone can be widespread. 4. The hormone binds to its target cells’ receptors, which may be either within the cell or in the plasma membrane. The binding of hormones to cellular receptors either initiates or inhibits Nerve selective metabolic activities within these cells (e.g., activate signal enzymes, open ion channels, stimulate protein synthesis or Interstitial cellular division). These altered metabolic activities can have fluid long-lasting effects and may continue after removal of the Endocrine Neurotransmitter Blood Target gland cell cells hormone. Capillary Note that many types of hormones are con- tinuously present within our blood at varying lev- Synapse els and are influencing our cells. Physicians and others are often provided critical information about an individual’s relative health or condition Synaptic vesicles containing by having a patient’s blood hormone levels mea- neurotransmitter sured. For example, low levels of thyroid hormone Synaptic cleft indicate that a patient has hypothyroidism (see sec- (a) Endocrine gland tion 17.8b), and the presence of human chorionic Target cell gonadotropin (hCG) indicates that a woman is Neurotransmitter receptor pregnant (see section 29.2c). (d) Neuron Figure 17.1 Nervous and Endocrine System Communication Methods. (a–c) In the endocrine system, hormones are secreted by WHAT DID YOU LEARN? endocrine cells. The hormones enter the blood and are transported throughout the body to reach their target cells. (d) In the nervous system, 1 Explain how hormones are moved between an endocrine gland and its neurons release neurotransmitters into a synaptic cleft to stimulate their target cells. target cells. 654 Chapter Seventeen Endocrine System 17.1b Comparison of the Two Control Systems functions of the endocrine system into the following four broad categories: LEARNING OBJECTIVE ∙∙ Regulating development, growth, and metabolism. Hormones 2. Compare and contrast the actions of the endocrine system and the nervous system to control body function. have regulatory roles in both cell division and cell differentiation, which occur during development and growth of the body. They The nervous system and endocrine system serve as the two comple- also control our metabolic activities—both anabolic (synthesis) mentary systems of control. However, the methods and effects of the and catabolic (degradation) processes. For example, growth two control systems differ. The nervous system exercises control hormone controls growth (see section 17.7d) and thyroid between two specific locations in the body by way of neurons hormone regulates cellular metabolism (see section 17.8b). (­figure 17.1d). Nerve signals trigger the release of neurotransmitter, ∙∙ Maintaining homeostasis of blood composition and volume. which crosses the synaptic cleft and binds to another neuron, a mus- Hormones regulate the amount of specific substances dissolved cle cell, or a gland cell to initiate a localized response of the target within blood plasma, such as glucose, amino acids, and ions cell, such as muscle contraction or gland secretion. The neurotrans- (e.g., Na+, Ca2+). Additionally, hormones also regulate other mitter is quickly degraded or taken back into the neuron. The characteristics of blood, including its volume, its cellular response induced by the nervous system is generally both rapid and concentration (erythrocytes and leukocytes), and number of short-lived. Notice, however, the two central features in common: platelets. Insulin, for example, regulates blood glucose levels (a) In response to stimuli, specialized cells of both systems release (see section 17.10b). chemical substances called ligands (hormones or neurotransmitters) ∙∙ Controlling digestive processes. Several hormones influence to communicate with particular target cells (see section 4.5b) and both the secretory processes and the movement of materials (b) the ligand binds to a cellular receptor in target cells to initiate a through the gastrointestinal tract in our digestive system. An cellular change. example is gastrin, which is released from the stomach and The general characteristics of these two complementary control controls digestive processes by increasing stomach contractions systems are compared in table 17.1. and secretions (see section 26.2d). ∙∙ Controlling reproductive a­ ctivities. Hormones affect both WHAT DID YOU LEARN? development and function of the reproductive system as 2 How does the endocrine system differ from the nervous system with well as expression of sexual behaviors. One example is respect to their target cells? prolactin. Prolactin, a hormone that influences reproductive activities, stimulates formation of breast milk by the mammary glands (see section 28.3f). 17.1c General Functions of the Endocrine System LEARNING OBJECTIVE WHAT DID YOU LEARN? 3. Describe the general functions controlled by the endocrine system. 3 Diabetes mellitus is noted by sustained high blood glucose levels. Which of the four functions listed is the most directly affected? The endocrine system (through the release of hormones) can com- municate with any body cell that has a receptor for that hormone. Consequently, its functions are very diverse. We have organized the 17.2 Endocrine Glands This section and the following three sections provide a general overview of four central features of the endocrine system. These include a discus- sion of (1) the ­location of the major endocrine glands and how they are Comparing the Endocrine System stimulated to release their hormones (see section 17.2); (2) the general Table 17.1 categories of hormones and their chemical structures (see section 17.3); and the Nervous System (3) how h­ormone molecules are transported within the blood (see sec­ Features Endocrine System Nervous System tion 17.4); and (4) how hormones interact with their target cells (see Communication Endocrine glands secrete A nerve signal causes section 17.5). Here we describe the major e­ ndocrine glands. Method hormones; hormones are neurotransmitter release transported within the from a neuron into a 17.2a Location of the Major Endocrine Glands blood to target cells synaptic cleft throughout body LEARNING OBJECTIVE Target of Any cell in the body Other neurons, muscle 4. List the major endocrine glands and their location within the body. Stimulation with a receptor for the cells, and gland cells hormone Endocrine glands are typically composed of a connective tissue Response Time Relatively slow reaction Rapid reaction time: framework, which houses and supports epithelial tissue that produces time: Seconds to minutes Typically milliseconds and releases hormones from their secretory cells. The secretory cells to hours or seconds are organized in two general ways: either as a single organ with only an Range of Effect Typically has widespread Typically has localized, endocrine function, or as cells housed in small clusters within organs effects throughout the specific effects in the or tissues that have some other primary function (figure 17.2). body body An endocrine organ is a single organ that is entirely endocrine Duration of Long-lasting: Minutes to Short-term: in function. Endocrine organs include the pituitary gland, pineal Response days to weeks; may Milliseconds; terminates gland, thyroid gland, parathyroid glands, and adrenal glands. continue after stimulus is with removal of stimulus Some endocrine cells are housed in tissue clusters within specific removed organs or tissues. These cells secrete one or more hormones, but the organs Chapter Seventeen Endocrine System 655  Major endocrine glands Organs/tissues containing endocrine cells Figure 17.2 Location of the Major Endocrine Glands, Organs, and Tissues Containing Endocrine Parathyroid glands Hypothalamus Cells. The left side of this image identifies organs that are entirely endocrine in Pituitary function. The right side shows organs and gland tissues that serve some other primary Pineal function and contain endocrine cells that gland secrete one or more hormones. Posterior surface of Thyroid (Note: The placenta is not shown in this thyroid gland gland figure; see figure 29.7.) Skin Adrenal cortex Thymus Adrenal Heart medulla Liver Adrenal gland Stomach Adrenal glands Pancreas Small intestine Adipose connective tissue Kidney Gonads Testes (male) Ovaries (female) have some other primary function as well. These organs and tissues include hormone. An example occurs when thyroid-stimulating the hypothalamus, skin, thymus, heart, liver, stomach, pancreas, small intes- ­hormone (which is released from the anterior pituitary) binds tine, adipose connective tissue, kidneys, and gonads (testes and ovaries). to the t­hyroid gland to cause release of thyroid hormone Note that the term endocrine gland will be used throughout the (figure 17.3a). rest of this chapter when referring either to an endocrine organ or an ∙∙ Humoral stimulation. Some endocrine glands are organ or tissue containing endocrine cells. The major endocrine glands stimulated to release their hormones in response to a of the body are listed in table 17.2. This table includes the hormones changing level of nutrients (e.g., glucose) or ions produced by each gland, the primary target organs or tissue, and the (e.g., Ca2+) within the blood. (The term humoral is a primary function(s) of each hormone. historical term related to blood as one of the four “humors,” or fluids, of the body.) When either the nutrient WHAT DID YOU LEARN? or ion levels decrease or increase within the blood, an 4 What are the major endocrine organs in the human body? What are endocrine gland is stimulated to release its hormone the organs (or tissues) that have another primary function and contain molecules. An example of humoral stimulation occurs endocrine cells? when blood glucose increases and the pancreas releases insulin (figure 17.3b). 17.2b Stimulation of Hormone Synthesis and Release ∙∙ Nervous system stimulation. A few endocrine glands are stimulated to release hormone(s) by direct stimulation from LEARNING OBJECTIVE the nervous system. The classic example is the release of 5. Explain the three reflex mechanisms for regulating secretion of hormones. ­epinephrine and norepinephrine by the adrenal medulla in response to stimulation by the sympathetic division of the The regulated secretion of a hormone from an endocrine gland is con- autonomic nervous system (figure 17.3c). trolled through a reflex (see section 14.6a). Reflexes occur in both the nervous system and the endocrine system. Endocrine reflexes are initiated by one of three types of stimulation: hormonal stimulation, WHAT DID YOU LEARN? ­humoral stimulation, or nervous system stimulation (figure 17.3). 5 Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex to release cortisol hormone. This is an example of what type of stimulation: ∙∙ Hormonal stimulation. The stimulus for the release of many (a) hormonal, (b) humoral, or (c) nervous system? hormones from an endocrine gland is the binding of another 656 Chapter Seventeen Endocrine System  Table 17.2 Endocrine Glands and Organs Containing Endocrine Cells Major Hormone(s) Primary Target Gland Produced Organ/Tissue Primary Function(s) of the Hormone Hypothalamus Regulatory hormones Anterior pituitary Control release of hormones from anterior pituitary Antidiuretic hormone (ADH)1 Kidney; hypothalamus Stimulates the kidneys to decrease urine output and the thirst center to (vasopressin) (thirst center); blood vessels increase fluid intake when the body is dehydrated; in high doses, ADH is a vasoconstrictor (thus, it is also called vasopressin) Oxytocin1 Uterus; breast Contraction of smooth muscle of uterus; ejection of milk from mammary (mammary glands); brain glands; increases feelings of emotional bonding between individuals Pituitary gland Thyroid-stimulating hormone (TSH) Thyroid gland Stimulates thyroid gland to release thyroid hormone (anterior) Prolactin (PRL) Breast (mammary glands) Regulates mammary gland growth and breast milk production in females; function not fully known in males Follicle-stimulating hormone Ovary; testis Controls development of both oocyte and ovarian follicle (spherical (FSH) structure that houses an oocyte) within ovaries; controls development of sperm within testes Luteinizing hormone (LH) Ovary; testis Induces ovulation of secondary oocyte from the ovarian follicle; controls testosterone synthesis within testes Adrenocorticotropic hormone Adrenal cortex Stimulates adrenal cortex to release corticosteroids (e.g., cortisol) (ACTH) Growth hormone (GH) Liver; skeleton; muscle; Release of insulin-like growth factors (IGFs) from liver; GH and IGFs all cells function synergistically to induce growth Pineal gland Melatonin Brain Helps regulate the body’s circadian rhythms (biological clock); functions in sexual maturation Thyroid gland Thyroid hormone All cells Increase metabolic rate of all cells; increase heat production (calorigenic effect) Calcitonin Bone; kidney Decreases blood calcium levels; most significant in children Parathyroid glands Parathyroid hormone (PTH) Bone tissue; kidney Increases blood calcium levels by stimulating both release of calcium from bone tissue and decrease loss of calcium in urine; causes formation of calcitriol hormone (a hormone that increases calcium absorption from small intestine) Thymus Thymosin, thymulin, T-lymphocytes (a type of Maturation of T-lymphocytes (a type of white blood cell, or leukocyte) thymopoietin white blood cell) Adrenal cortex Mineralocorticoids (e.g., Kidney Regulate blood Na+ and K+ levels by decreasing the Na+ and increasing aldosterone) the K+ excreted in urine Glucocorticoids (e.g., cortisol) Liver; adipose connective Participate in the stress response; increase nutrients (e.g., glucose) that are tissue; all cells available in the blood Gonadocorticoids (e.g., dehydro- Various body cells Stimulate maturation and functioning of reproductive system epiandrosterone [DHEA]) Adrenal medulla Epinephrine (EPI) and Various body cells Prolong effects of the sympathetic division of the autonomic nervous system norepinephrine (NE) Pancreas Insulin Liver; adipose connective Decreases blood glucose levels tissue; most body cells Glucagon Liver; adipose connective tissue Increases blood glucose levels Testes (gonads) Testosterone Reproductive organs; various Stimulates maturation and function of male reproductive system body cells Inhibin Anterior pituitary Inhibits release of follicle-stimulating hormone (FSH) from anterior pituitary Ovaries (gonads) Estrogen and progesterone Reproductive organs; various Stimulate maturation and function of female reproductive system body cells Inhibin Anterior pituitary Inhibits release of follicle-stimulating hormone (FSH) from anterior pituitary Heart Atrial natriuretic peptide (ANP) Kidneys; blood vessels Functions primarily to decrease blood pressure by stimulating both the kidneys to increase urine output and the blood vessels to dilate Kidneys Erythropoietin (EPO) Bone (red bone marrow) Increases production of red blood cells (erythrocytes) Liver Angiotensinogen Blood vessels; kidney; Converted by enzymes released from the kidney and within the inner lining of hypothalamus (thirst center) blood vessels to angiotensin II; increases blood pressure by causing vasoconstriction and decreasing urine output; stimulates thirst center Insulin-like growth factors (IGFs) Various body cells Function synergistically with growth hormone to regulate growth Erythropoietin (EPO) Bone (red bone marrow) Increases production of red blood cells (erythrocytes); note that kidneys are the major producers of EPO Hepcidin Small intestine and Regulates iron levels macrophages of liver, spleen, and bone marrow Stomach Gastrin Stomach Facilitates digestion within stomach Small intestine Secretin Digestive organs Regulates digestion within small intestine by helping to maintain normal pH within small intestine Cholecystokinin (CCK) Digestive organs Regulates digestion within small intestine by facilitating digestion of proteins and fats within small intestine Motilin Small intestine Stimulates small intestine motility Skin Vitamin D3 Bone; kidney; small intestine Converted by enzymes of liver and kidney to calcitriol; functions synergistically with PTH and increases calcium absorption from small intestine Adipose connective Leptin Brain Helps regulate food intake tissue 1. These hormones are produced by the hypothalamus but stored and released in the posterior pituitary. Chapter Seventeen Endocrine System 657  Hormonal stimulation: Humoral stimulation: Nervous system stimulation: Release of another hormone Changes in level of nutrient or ion in the Stimulation by the nervous system triggers release of the hormone blood triggers release of the hormone triggers release of the hormone 1 Anterior pituitary releases thyroid-stimulating 1 Blood glucose levels increase. 1 Sympathetic division is activated. hormone (TSH). Pancreas Spinal cord Nerve signal Anterior pituitary Insulin Adrenal medulla Preganglionic axon 2 TSH stimulates TSH thyroid gland to 2 Sympathetic release thyroid 2 Increased preganglionic hormone (TH). blood glucose axons stimulate Thyroid stimulates gland Increased adrenal medulla pancreas to blood to release release insulin. glucose epinephrine and Epinephrine and TH norepinephrine. Capillary norepinephrine (a) (b) (c) Figure 17.3 Types of Endocrine Stimulation. An endocrine gland can be stimulated to release its hormone in response to (a) hormonal stimulation, (b) humoral stimulation, or (c) nervous system stimulation. adrenal cortex (e.g., corticosteroids such as cortisol, and mineralo- 17.3 Categories of Hormones corticoids such as aldosterone). Hormones are organized (by some experts) into two broad categories Calcitriol is the hormone produced from vitamin D (see based upon whether the hormone molecules are transported within ­section 7.6a), and it is sometimes classified as a steroid hormone. How- the blood. Circulating hormones are transported within the blood ever, it is more accurately classified as a sterol hormone, a slightly (as described in section 17.1a), whereas local hormones are short- different molecule but one that is also lipid-soluble. lived molecules that influence cells within the local tissue from Biogenic Amines which they are produced. Biogenic amines are also called monoamines. They are modified 17.3a Circulating Hormones amino acids (modification involves removal of a carboxyl functional group from an amino acid) (figure 17.4b). Biogenic amines include the LEARNING OBJECTIVES catecholamines (e.g., epinephrine, norepinephrine) released from the 6. Name the three structural categories of circulating hormones, and give adrenal medulla, thyroid hormone released from the thyroid gland, and examples within each category. melatonin from the pineal gland. Biogenic amines are water-­soluble 7. Distinguish the hormones that are lipid-soluble from those that are water- except for thyroid hormone. Thyroid hormone is lipid-soluble because soluble. it is produced from two tyrosine amino acids (see figure 17.16), which are amino acids that contain a nonpolar ring. Circulating hormones are grouped according to their chemical struc- ture into three general categories: steroids, biogenic amines, and Proteins proteins. These regulatory molecules are synthesized within endo- Most hormones are proteins. These are molecules composed of small crine cells from either (a) cholesterol, which is a type of lipid with a chains of amino acids and include small peptides, large polypeptides, four-ring structure (see section 2.7b), or (b) amino acids, which are and glycoproteins (figure 17.4c). All hormones in this category are the monomers that compose proteins (see section 2.7e). Cholesterol water-soluble. molecules are modified in the synthesis of steroid hormones. Amino acids are the building blocks for both biogenic amines and protein WHAT DID YOU LEARN? hormones. An example of each category is shown in ­figure 17.4. As 6 Identify which of the following hormone categories are lipid-soluble: you read about the chemical structure of these hormones, please note (a) reproductive hormones produced in the gonads, (b) adrenal cortex whether the molecules in each category are lipid-soluble or water- hormones, and (c) thyroid hormone. soluble. This difference in solubility influences both the transport of 7 What two events or processes associated with a hormone are influenced the hormone in the blood and how it interacts with its target cells. by whether a hormone is lipid-soluble or water-soluble? Steroids 17.3b Local Hormones Steroids are lipid-soluble molecules synthesized from cholesterol LEARNING OBJECTIVES (figure 17.4a). This category includes both the hormones produced within the gonads (e.g., estrogen and progesterone in the ovaries and 8. Describe the general structure, formation, and function of local hormones. testosterone in the testes) and the hormones synthesized by the 9. Compare autocrine and paracrine signaling that occurs through local hormones. 658 Chapter Seventeen Endocrine System  Steroids Biogenic amines Proteins Lipid-soluble Water-soluble (except thyroid hormone) Water-soluble Formed from cholesterol Derived from amino acid that is Consists of amino acid chains modified (e.g., tyrosine) CH2OH C O H2 N CH2 H3C HO OH HO CH2 H2 N H3C HO O OH COOH Examples: Estrogen, progesterone, Examples: Norepinephrine, epinephrine, Examples: Antidiuretic hormone, insulin, glucagon, testosterone, cortisol, aldosterone thyroid hormone, melatonin growth hormone, erythropoietin (a) (b) (c) Figure 17.4 Hormone Types. The three types of hormones are steroids, biogenic amines, and proteins. (a) Steroids (which include hormones released from both the gonads and adrenal cortex) are lipid-soluble and formed from cholesterol. In comparison, (b) biogenic amines (which include hormones released from the adrenal medulla, thyroid hormone, and melatonin) and (c) proteins (which include most hormones) typically are water-soluble and formed from amino acids. Local hormones are a large group of short-lived signaling molecules WHAT DO YOU THINK? that do not circulate within the blood. Instead, cells synthesize and release these molecules, which then bind with either the same cell that 1 Given the examples of prostaglandin activity just described, provide produced them (autocrine stimulation) or neighboring cells (paracrine examples of why an individual might take aspirin, which blocks the synthesis of prostaglandins (see Clinical View 17.1: “Synthesis of stimulation). These signaling molecules have properties similar to hor- Eicosanoids”). mones because the released ligands (signaling molecules) initiate and regulate cellular changes. They just do so “in the tissue neighborhood.” WHAT DID YOU LEARN? Eicosanoids (ı̄′kō-să-noydz; eicosa = twenty, eidos = formed), 8 Prostaglandins from damaged tissue cause smooth muscle in local blood which were first introduced in section 2.7b, are the primary type of vessels to vasodilate (increase the diameter of the vessel lumen). Is this an local hormones. Eicosanoids include prostaglandins, thromboxanes, example of (a) autocrine stimulation or (b) paracrine stimulation? Explain. and leukotrienes (figure 17.5). Each of these signaling molecules is formed from a 20-carbon fatty acid (specifically arachidonic acid), which is cleaved from a phospholipid molecule of a cell’s plasma membrane. Their production is not limited to one endocrine gland (as INTEGRATE circulating hormones typically are), but instead are synthesized by cells composing many tissues located throughout the body. Thus, eicosanoid synthesis and release provides the means for all tissues to CONCEPT CONNECTION locally regulate cellular responses. Prostaglandins, thromboxanes, and leukotrienes are local hormones that can Prostaglandins are the most diverse category of eicosanoids (e.g., act as local vasoactive substances (substances that change the size of blood prostaglandin D, E, and F with various subtypes such as prostaglandin E2 vessels by narrowing blood vessels through vasoconstriction or widening [PGE2]). Their effects are wide-ranging, depending upon both the specific blood vessels through vasodilation). The role of leukotrienes and thromboxanes type of prostaglandin molecule and the specific type of cellular receptor as a vasoconstrictor to prevent blood loss is described in section 20.4c. In to which it binds. Examples of prostaglandin activity include (a) stimulat- comparison, the role of prostaglandins as vasodilators (as part of the ing the hypothalamus to raise body temperature to induce a fever, inflammatory response) is discussed in section 22.3e. (b) inhibiting stomach acid secretion, (c) acting on mast cells to release molecules that increase inflammation, and (d) stimulating pain receptors. 17.4 Hormone Transport Plasma Prostaglandins Membrane Hormone molecules are transported within the blood to target cells 20-carbon fatty acid Thromboxanes following their release from the endocrine gland that synthesized (Arachidonic acid) them (see figure 17.1). Here we consider how both lipid-soluble and Leukotrienes water-soluble hormones are transported and the factors that influence the level of circulating hormone. Eicosanoids Figure 17.5 Eicosanoid Formation. Eicosanoids include 17.4a Transport in the Blood prostaglandins, thromboxane, and leukotrienes. These local hormones are LEARNING OBJECTIVE synthesized by an enzymatic cascade that begins with a 20-carbon fatty acid, which is removed from phospholipids within a plasma membrane. 10. Compare the transport of lipid-soluble hormones with that of water-soluble hormones. Chapter Seventeen Endocrine System 659  maintaining of a given homeostatic level (or steady state) of the INTEGRATE physiologically active, unbound hormone that is required. The bound hormone simply serves as a readily available source within the blood. CLINICAL VIEW 17.1 Water-soluble hormones (i.e., most biogenic amines and proteins), Synthesis of Eicosanoids in comparison, readily dissolve within the aqueous environment of the blood, and so these hormones do not generally require carrier proteins. Eicosanoids are formed from phospholipid molecules within the plasma Thus, water-soluble hormones are generally released directly into the membrane. The enzyme phospholipase A2 releases a 20-carbon fatty acid blood and transported to target cells. Note that some water-soluble hor- called arachidonic acid. (This enzyme is inhibited by steroid drugs [e.g., mones (e.g., insulin-like growth factor) are transported by carrier pro- hydrocortisone] to prevent formation of all eicosanoids.) Arachidonic acid is teins, which function to prolong the life of these hormones. then acted upon by either (a) cyclooxygenase, which converts arachidonic acid to prostaglandins and thromboxanes (this enzyme is inhibited by aspirin to prevent formation of both of these eicosanoids) or (b) lipoxygenase, which WHAT DID YOU LEARN? converts arachidonic acid to leukotrienes (this enzyme is inhibited by St. John’s 9 Why are carrier proteins necessary for lipid-soluble hormones? wort to prevent formation of leukotrienes). 10 What is the added benefit of a carrier protein? 17.4b Levels of Circulating Hormone Cytosol LEARNING OBJECTIVES Plasma membrane phospholipid 11. Describe the two primary factors that affect the concentration level of a circulating hormone. Interstitial fluid 12. Explain what is meant by the half-life of a hormone. Phospholipase A2 [Steroid drugs block here] Hormones exert their physiologic effects primarily as a result of their Arachidonic acid (20-carbon fatty acid) blood concentration. Consequently, the amount of each hormone must be tightly regulated to prevent potential clinical consequences, such as organ or tissue malfunction and disease. For example, decreased meta- bolic rate is caused by low blood levels of thyroid hormone, whereas Cyclooxygenase Lipoxygenase [NSAIDs (e.g., aspirin) [St John’s wort gigantism is due to high blood levels of growth hormone (see Clinical blocks here] blocks here] View 17.4: “Disorders of Growth Hormone Secretion”). There are two primary factors that interact to influence hormone ­concentration—hormone release and hormone elimination: Prostaglandins Thromboxanes Leukotrienes ∙∙ Hormone release. Hormone release from an endocrine gland and hormone concentration within the blood are positively Eicosanoids correlated. An increase in release of the hormone results in a higher hormone concentration within the blood. In contrast, a decrease in release of the hormone results in a lower ­hormone concentration within the blood. ∙∙ Hormone elimination. Hormones are typically eliminated Lipid-soluble hormones (e.g., steroids, calcitriol, thyroid hormone) (a) through enzymatic degradation, which usually occurs in do not dissolve readily within the aqueous environment of the blood liver cells, (b) through removal of the hormone from the (blood plasma), and so they require a carrier protein. These mol- blood by its excretion from the kidneys as a component of ecules are water-soluble proteins synthesized by the liver. Think of urine, or (c) by uptake into target cells. Hormone elimination these proteins as boats that “ferry” the hormone molecules within and hormone concentration in the blood are negatively the blood. Some hormone carrier proteins may be very ­selective, correlated. The faster the rate of hormone elimination, the binding and transporting only one specific lipid-soluble molecule lower the hormone concentration within the blood, whereas (e.g., thyroxine-binding globulin), whereas other carrier proteins the slower the rate of hormone elimination, the higher the are nonselective (e.g., albumin), meaning they bind and transport hormone concentration within the blood. numerous lipid-soluble molecules. A carrier protein has the added benefit of protecting the hormone molecule and helping to prevent To maintain homeostatic levels of each hormone, a balance is required its early destruction (or, for small hormones, their loss in the urine). between its rate of release by its endocrine gland and its elimination Thus, the association of a hormone with a carrier protein often acts from the blood by the activities of the liver, kidney, and target cells. as a safeguard to help prolong the life of the hormone. Note that hormone release is typically maintained through negative The binding between a lipid-soluble hormone and a carrier pro- feedback (see section 1.6b) to maintain homeostatic blood levels of a tein is temporary. Hormone molecules bind to the carrier protein, hormone. For example, the release of insulin from the pancreas is detach from the carrier protein and float free within the blood, and increased in response to a rise in blood glucose level. However, as then may later reattach to a different carrier protein. Any hormone blood glucose level returns to normal (thus, removing the stimulus for that is attached to a carrier protein is a bound hormone, whereas an insulin release), the pancreas releases less insulin (see section 17.10b). unattached hormone is an unbound (free) hormone. Only unbound The release of some hormones from endocrine glands is regulated by hormone, which represents a very small fraction of the hormone positive feedback (see section 1.6c) in which progressively more of transported within the blood (0.1% to 10%), is generally able to exit the hormone is released—for example, the release of oxytocin from the blood and bind to cellular receptors of target organs. It is the the posterior pituitary during childbirth (see section 29.6c). 660 Chapter Seventeen Endocrine System  WHAT DO YOU THINK? 17.5 Target Cells: Interactions 2 What effect would impaired function of the liver or kidneys potentially have on hormone concentration in the blood: increase, decrease, or no with Hormones change? Explain. Hormones interact only with target cells (cells with receptors for those hormones) to initiate a specific cellular response. A specific hormone Half-Life generally has different types of target cells. For example, the hormone insulin binds with muscle cells, hepatocytes (liver cells), and adipose con- The half-life of a hormone is the amount of time necessary to reduce nective tissue cells. The greater the number of different target cells, the the hormone concentration within the blood to one-half of what had wider the potential influence that may be exhibited by a given hormone. been secreted originally (or measured previously). Generally, water- The specific process of how hormones interact with cell receptors, soluble hormones have a relatively short half-life, which amounts to and the cellular changes that are initiated, is significantly different for a few minutes or less for small peptides and about an hour for larger lipid-soluble hormones and water-soluble hormones. proteins. Steroids generally have the longest half-life, since their car- rier protein protects them from early destruction or loss. The half-life 17.5a Lipid-Soluble Hormones of testosterone, for example, is 12 days. Note that the shorter the half- life of a hormone, the more frequently it must be replaced to maintain LEARNING OBJECTIVE its normal concentration in the blood. 13. Describe how lipid-soluble hormones reach their target cell receptors and the type of cellular change they initiate. WHAT DID YOU LEARN? Lipid-soluble hormones (e.g., steroids, calcitriol) are relatively 11 What is the relationship of hormone synthesis to the concentration of that small, nonpolar molecules that are lipophilic (lip′ō-fil′ik), or lipid- hormone in the blood? loving. Recall that the plasma membrane is not an effective barrier to small, nonpolar molecules (see section 4.3a). Consequently, unbound lipid-soluble hormones such as steroids are able to diffuse across the plasma membrane. Upon entering the cell, the hormone binds to intracellular receptors located in either the cytosol or nucleus to form a ­hormone-receptor complex (figure 17.6). 1 The unbound hormone diffuses readily through the plasma Unbound hormone membrane and binds with an 1 intracellular receptor, either within the cytosol or the nucleus to form Hormone a hormone-receptor complex (HRC). Bound hormone Carrier Hormone-receptor 2 The HRC binds with a specific protein Hormone complex DNA sequence called a receptor hormone-response element (HRE). 3 Binding of the HRC to the HRE stimulates mRNA synthesis. Hormone- receptor 4 mRNA exits the nucleus and Amino complex is translated by a ribosome in acids the cytosol. A new protein 2 is synthesized. Blood Ribosome Nuclear mRNA DNA envelope Hormone- response element 3 mRNA 4 synthesis mRNA Plasma Protein membrane Figure 17.6 Lipid-Soluble Interstitial fluid Cytosol Nucleus Hormones and Intracellular Receptors. Lipid-soluble hormones enter a cell and ultimately cause the formation of new protein. Chapter Seventeen Endocrine System 661  Water-soluble hormone 1 Hormone (first messenger) binds to receptor and GDP: Guanine diphosphate induces shape change to activate the receptor. GTP: Guanine triphosphate Receptor protein Hormone Interstitial fluid Activated receptor Interstitial fluid Cytosol 2 G protein Cytosol binds to Activated G protein activated G protein receptor. 3 GDP is “bumped off” GTP Inactive GTP G protein and GTP binds to 4 Activated G protein (with GTP) is released from the GDP G protein; G protein receptor and moves along the inside of the plasma GDP is then activated. membrane, which results in formation or availability of second messenger (see figure 17.8). (a) Inactive G protein (b) Activated G protein Figure 17.7 Activation of a G Protein. An inactive G protein (a) is activated (b) in response to a water-soluble hormone binding to a plasma membrane receptor. The hormone-receptor complex formed within the target cell then INTEGRATE binds to a particular DNA sequence called a ­ hormone-response element (HRE). Binding to a specific DNA sequence results in synthesis LEARNING STRATEGY 17.1 (transcription) of messenger ribonucleic acid (mRNA). Subsequent trans- lation of this mRNA by ribosomes synthesizes a specific protein (see section The interaction of water-soluble hormones and a target cell can be likened 4.8b). The change in protein synthesis pattern within the cell may result to a courier delivering a letter to a mansion. in either an alteration in cell structure (e.g., as occurs with a greater level The courier delivering the message plays the part of the hormone. of sex hormones during puberty) or a shift in the target cells’ metabolic He knocks on the mansion door (the receptor). activities if the newly synthesized proteins are enzymes. Consider, for A butler (the G protein) answers the door and receives the message but example, that an increase in testosterone results in larger muscles due to denies entry to the courier. formation of contractile proteins, a deeper voice from longer and thicker The message is passed along to various assistants before vocal cords, and facial hair growth. These effects induced by testosterone reaching the owner of the mansion (a series of events representing reflect a cellular increase in protein synthesis. the intracellular enzymatic cascade). The owner then brings about a change in home activities based on the message. WHAT DID YOU LEARN? 12 Where are lipid-soluble hormone receptors located? What is the general cellular change that occurs with binding of a lipid-soluble hormone? Hormone Binding and the Activation of G Protein Both of the two common signal transduction pathways function through 17.5b Water-Soluble Hormones an internal plasma membrane protein complex called a G protein (first LEARNING OBJECTIVE introduced in section 4.5b). This protein is named based upon its ability to bind guanine nucleotide (a nucleotide containing the base guanine; 14. Describe how water-soluble hormones induce cellular change in their target see section 2.7d). Guanine diphosphate (GDP) is bound to G protein cells. when it is in the inactive form, and guanine triphosphate (GTP) is Water-soluble hormones (e.g., proteins and biogenic amines, except bound when G protein is in the activated form. The binding of hormone thyroid hormone) are polar molecules and are unable to cross the to a plasma membrane receptor causes a change in G protein from its plasma membrane. Denied entry into the cell, water-soluble hor- inactive form to its activated form. The sequence of this occurrence is mones instead must use an alternative, slightly more complex way to depicted and described in detail in f­ igure 17.7. stimulate a target cell. This stimulation is initiated when the hormone Subsequent to its formation, activated G protein then generally binds to a plasma membrane receptor. activates (or inhibits) one of two plasma membrane enzymes associat- The binding of water-soluble hormones to a plasma membrane ed with different intracellular enzymatic cascades: adenylate cyclase or receptor initiates a series of biochemical events across the membrane phospholipase C. A cell may have either or both enzymatic cascades. called a signal transduction pathway. In this pathway, the hormone is the signaling molecule, or first messenger. Its binding to the Adenylate Cyclase Activity receptor results in the formation of a different molecule within the Activated G protein moves along the inside of the plasma membrane, cell called the second messenger. The second messenger then modi- where it binds to the plasma membrane protein adenylate (a-den′i-lāt) fies some cellular activity. The mechanisms of initiating cellular cyclase (figure 17.8a). Activated adenylate cyclase increases the changes are described here for the two most common signal transduc- formation of the second messenger, cAMP (3',5'-cyclic adenosine tion pathways, which involve either adenylate cyclase activity or mono­phosphate) from ATP. The cAMP then activates a protein ­kinase phospholipase C activity. (specifically protein kinase A), an enzyme that phosphorylates (adds 662 Chapter Seventeen Endocrine System  Adenylate cyclase Interstitial fluid Plasma membrane 1 Ac 1 Activated G protein binds to and causes activation 2 of the plasma membrane enzyme adenylate Cytosol cAMP cy cyclase. ATP 2 Adenylate cyclase converts ATP molecules to GTP cAMP molecules. Activated G protein 3 3 cAMP serves as the second messenger by Activated activating protein kinase A (a phosphorylating protein kinase A enzyme that adds phosphate to other molecules; these molecules may be activated or inhibited as a result). (a) Activated G protein “turns on” adenylate cyclase. Phospholipase Phosph Phospholi spholipas ol oli pase pas eC Ion channel chann channel el Interstitial Inter Inter Intersti titi titi tiall fl fluid uid id PIP2 1 1 Activated Activate ed G protein binds to and causes activation Activated Activated Act Activa iva vate ted ted of the plasma plasm membrane enzyme phospholipase C. p D DAG DA DA DAG DAG Cytosol Cy ytosol protein 3c 3a kinase kinase C Phospholipa C splits PIP2 into two second 2 Phospholipase 2 messengers: messen ngers DAG (diacylglycerol) and IP3 (inositol GTP triphosphate). triphosp phate Ca2+ Activated Calmodulin G protein 3a DAG activates activat protein kinase C (a phosphorylating IP P3 enzyme). enzyme e). 3b IP3 increase Ca2+ in cytosol by stimulating Ca2+ increases release from the endoplasmic reticulum (ER) (and 3b a2+ Ca 3c entry ac across cross the plasma membrane from the interstitial interstit ial fl fluid, which is not shown in figure). Endoplasm Endoplasmic Endopl asmic ic reticulum reticu reticulum iculum Actiiiva Act A ate Activateded d protein pro pr otein ote o in 3c Ca2+ act acts ts as a third messenger to activate protein kinase enzymes k kinase enzyymes e enzy e kinase enzymes (Ca2+ does this directly or by first binding to ccalmodulin). Ca2+ may also alter activity (b) Activated G protein “turns on” phospholipase C. of ion ch hann channels within the plasma membrane. Figure 17.8 Action of G Proteins. Following its activation, G protein is an intracellular molecule that moves along the inside of the plasma membrane and can stimulate other molecules. Two of the most common are (a) adenylate cyclase, which forms cyclic AMP second messenger, and (b) phospholipase C, which causes formation of DAG and IP3 second messengers. Pathways involving G protein ultimately result in the activation of kinase enzymes, which activate or inhibit other enzymes through phosphorylation, change cell permeability, or both. phosphate to) other molecules (see section 3.3g). Phosphorylation results protein kinase (here, protein kinase C). This enzyme, in turn, phos- in activation or inhibition of these molecules. Examples of hormones that phorylates other molecules. function through the activation of adenylate c­yclase include thyroid- stimulating hormone (see section 17.8b) and glucagon (see section 17.10b). Action of IP3 IP3 is a second messenger that diffuses from the plasma membrane into the cytosol. It increases intracellular Ca2+ Phospholipase C Activity concentration by interacting either with the endoplasmic reticu- The second possibility as a result of G protein activation occurs when lum, causing the release of stored Ca2+, or with Ca2+ channels in it binds with a different plasma membrane protein called the plasma membrane (not shown in figure), permitting Ca2+ entry ­phospholipase C (fos′fō-lip′ās) (figure 17.8b). Activation of phospho- from the interstitial fluid. Increased intracellular Ca2+ acts as a lipase C results in the splitting of PIP2 (phosphatidylinositol third messenger within the cytosol (a) ­to activate protein kinase bisphosphate), a phospholipid molecule within the plasma membrane. enzymes directly, or by first binding with an intracellular protein The splitting of PIP2 results in the formation of two secondary mes- called calmodulin, or (b) to alter plasma membrane permeability senger molecules: DAG (diacylglycerol; dī′as-il′glis′ĕr-ōl) and IP3 by binding to specific ion channels ­located within the plasma (­inositol; in-ō′si-tōl, -tol) triphosphate. membrane and changing the flow of that specific ion either into or out of the cell. Examples of hormones that function through the Action of DAG DAG is a second messenger that remains in the activation of phospholipase C include oxytocin and anti­diuretic plasma membrane. It is similar in action to cAMP in that it activates a hormone (see section 17.7b).