137 Hormones As Signaling Molecules Hormones Are Chemical Messengers That Enable Communication Between Cells in Different Parts of the Body
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contents Principles of Biology 137 Hormones as Signaling Molecules Hormones are chemical messengers that enable communication between cells in different parts of the body.
A blacktailed prairie dog consumes a meal. As this blacktailed prairie dog (Cynomys ludovicianus) consumes its meal, hormones regulate digestion and blood glucose levels. Millard H. Sharp/Science Source.
Topics Covered in this Module
Intercellular Signaling Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Transmission of Hormonal Signals Signal Transduction by Steroid Hormones
Major Objectives of this Module
Compare the five types of intercellular signaling. Explain how pheromones enable communication between individuals. Describe how watersoluble and lipidsoluble hormones transmit signals.
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137 Hormones as Signaling Molecules
Intercellular Signaling Cells must be able to communicate so that an animal can respond to its environment and carry out normal physiological functions. Mechanisms of intercellular communication can be divided into five broad categories based on how the signal is transmitted and the distance it travels.
Autocrine signaling. In autocrine signaling, a cell responds to a chemical signal that it secretes, often to amplify or maintain a physiological response. The chemical signaling molecule, called a local regulator, only acts a short distance from where it is secreted. Autocrine signaling is involved in differentiation of T cells of the adaptive immune system. When a T cell binds antigen associated with major histocompatibility complex, it secretes a local regulator called interleukin2 (IL2). IL2 binds an IL2 receptor present on the T cell, causing it to undergo clonal expansion. During clonal expansion, the T cell divides and differentiates.
Paracrine signaling. Paracrine signaling elicits responses in cells close to the signaling cell. Like autocrine signaling, paracrine signaling is mediated by local regulators. Paracrine signaling plays a key role in embryonic development because local regulators are used to mediate limb development. Because local regulators act over a short distance, limb development occurs only in specific regions of the body.
Endocrine signaling. In endocrine signaling, a chemical called a hormone circulates in blood or hemolymph from the cell that secretes it to the target cell. Cells that secrete hormones, called endocrine cells, are part of the endocrine system. Some endocrine cells are found in tissues of various organs, such as the stomach. Other endocrine cells are organized into endocrine glands. Endocrine signaling permits communication between distant cells in an animal. Many physiological functions are regulated by the endocrine system, including digestion, metabolism, salt balance, growth and development, and reproduction.
Synaptic signaling. Synaptic signaling occurs at the junctions, or synapses, between a neuron and another cell. Neurons, specialized cells of the nervous system, have long extensions called dendrites and axons that form specific pathways along which information is transferred. There are two types of synapse, electrical synapses and chemical synapses. Electrical synapses are direct electrical connections between two neurons. Movement of ions through channels called gap junctions allows an electrical signal to be transferred from one neuron to the other. Communication through gap junctions is often bidirectional, meaning it can travel in both directions, and very fast. For this reason, electrical synapses are used in defensive reflexes. However, electrical synapses do not allow signal amplification.
In chemical synapses, chemicals called neurotransmitters transmit a message between a neuron and another cell, which may be a neuron or a muscle cell. Binding of neurotransmitters to receptors on the receiving cell triggers a response. Neurotransmitters often activate a signal transduction cascade that amplifies the signal. Communication through chemical synapses is unidirectional. Chemical synapses are involved in behavioral responses, learning, and memory.
Neuroendocrine signaling. In neuroendocrine signaling, stimulation of specialized neurons causes the release of signaling molecules called neurohormones into the bloodstream. Neurohormones can travel throughout the body and affect distant cells in the same way hormones do.
IN THIS MODULE
Intercellular Signaling Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Transmission of Hormonal Signals Signal Transduction by Steroid Hormones Summary Test Your Knowledge
WHY DOES THIS TOPIC MATTER?
Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cuttingedge research lead to prevention and treatment strategies that could make cancer obsolete?
PRIMARY LITERATURE
Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download http://www.nature.com/principles/ebooks/principlesofbiology104015/29145721/1 1/2 1/27/2015 Hormones as Signaling Molecules | Principles of Biology from Nature Education
Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Singlechannel currents recorded from membrane of denervated frog muscle fibers. View | Download
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contents Principles of Biology
137 Hormones as Signaling Molecules
Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Many animals are able to communicate with members of their own species using signaling molecules called pheromones that are emitted into the environment. For example, an ant that has found food will release pheromones on the way back to the nest, creating a pheromone trail that other ants can follow (Figure 1). Sex pheromones signal the mating availability of a female. The effect of some pheromones may not be global to all members of a species but may be limited to individuals of a specific colony or family.
Figure 1: Ant pheromones. Ants such as this harvester ant (Messor barbarus) can follow a pheromone trail left by another ant to find a food source. Richard Becker/FLPA/Science Source.
IN THIS MODULE
Intercellular Signaling Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Transmission of Hormonal Signals Signal Transduction by Steroid Hormones Summary Test Your Knowledge
WHY DOES THIS TOPIC MATTER?
Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cuttingedge research lead to prevention and treatment strategies that could make cancer obsolete?
PRIMARY LITERATURE
Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download
Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Singlechannel currents recorded from membrane of denervated frog muscle fibers. View | Download
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contents Principles of Biology
137 Hormones as Signaling Molecules
Transmission of Hormonal Signals When a hormone binds to a protein receptor, a conformational change in the receptor occurs that triggers a response. A particular hormone only affects cells expressing a receptor to which it binds. In some cases, different receptors for a particular hormone are found in different cells types. Thus, a particular hormone may trigger different responses in different cells. For example, different receptors for the hormone epinephrine (also called adrenaline) are expressed in cardiac cells and hepatocytes (liver cells). Epinephrine, which is involved in the fightorflight response, binds to receptors called adrenergic receptors. The adrenergic receptor expressed in cardiac cells causes the heart to beat faster, while the adrenergic receptor expressed in the liver stimulates the breakdown of glycogen.
Hormones are classified into two types based on solubility (Figure 2). Watersoluble hormones, which include proteins and hydrophilic molecules, cannot diffuse through plasma membranes. Thus, these hormones are released from endocrine cells by exocytosis. They diffuse into the bloodstream and travel to the target cell, where they bind an extracellular receptor. Hormone binding causes a conformational change in the receptor that causes a transfer of the signal from the outside of the cell to the inside, a process called signal transduction.
Lipidsoluble hormones are able to cross the plasma membrane of both the endocrine cell from which they are secreted and the target cell on which they act. However, lipidsoluble molecules tend to form nonfunctional aggregates in the aqueous environment of the blood, so specialized transport proteins, which are also called binding globulins, are required to transport lipidsoluble molecules through the blood. Most receptors for lipidsoluble hormones, which are located inside the cell, are able to move into the nucleus and bind DNA, causing a change in gene expression. However, some receptors for lipidsoluble hormones are located on the cell surface. These cellsurface receptors activate a signal transduction cascade similar to the one activated by watersoluble hormones.
Figure 2: Transmission pathways of watersoluble and lipidsoluble hormones. Watersoluble hormones (left), which cannot pass through the plasma membrane, bind to a receptor on the outside of the target cell. Signal transduction transfers the signal from the outside of the cell to the inside. Lipidsoluble hormones (right), which can diffuse through cell membranes, often bind intracellular receptors that directly mediate a cellular response. © 2014 Nature Education All rights reserved. Test Yourself
How do lipid and watersoluble hormones differ in how they travel through the bloodstream?
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Epinephrine signal transduction pathway. The epinephrine signal transduction pathway that occurs in hepatocytes is shown in Figure 3. Epinephrine binds adrenergic receptors, which are members of a larger family of cell surface receptors known as G proteincoupled receptors. G proteincoupled receptors contain seven membranespanning domains and interact with intracellular signal transduction molecules called G proteins. In the absence of signal, G proteins are bound to GDP, a nucleotide http://www.nature.com/principles/ebooks/principlesofbiology104015/29145721/3 1/4 1/27/2015 Hormones as Signaling Molecules | Principles of Biology from Nature Education
closely related to ATP. Binding of epinephrine to the adrenergic receptor induces a conformational change that allows the receptor to bind inactive G protein. The G protein exchanges GDP for GTP, which activates it. The activated G protein activates the enzyme adenylyl cyclase, which synthesizes cyclic adenosine monophosphate (cAMP) from ATP. cAMP is a second messenger, a molecule that transmits the hormonal signal from an activated receptor to other proteins in the cell. cAMP activates the enzyme protein kinase A (PKA). PKA phosphorylates other proteins, thereby activating them. At each step in the cascade, one activated molecule has the ability to activate numerous other molecules downstream in the cascade. This amplifies the original signal and results in a rapid, strong response that results in the breakdown of glycogen and the inhibition of glycogen synthesis. The result is the release of glucose into the blood.
Figure 3: The epinephrine signal transduction pathway in hepatocytes. Binding of epinephrine to its receptor triggers the activation of a G protein. The G protein activates adenylyl cyclase, which catalyzes the formation of cAMP. cAMP activates protein kinase A, which phosphorylates and activates other signal transduction molecules. © 2014 Nature Education All rights reserved. Test Yourself
For the epinephrine pathway in the liver, identify the signaling molecule, the target cell, the receptor for the signal, and the response by the target cell.
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Signal transduction by steroid hormones. Steroid hormones are a class of lipidsoluble hormones that are synthesized from cholesterol. Steroid hormones regulate a variety of cellular processes. For example, the steroid cortisol regulates fat and glucose metabolism, and aldosterone regulates blood pressure. Estrogens and androgens are sex steroid hormones. Estrogens include estradiol and progesterone. Testosterone is an androgen produced by the testes of the vertebrate male reproductive system and by the adrenal cortex in both males and females. Figure 4 shows a simplified signal transduction pathway for testosterone. When testosterone enters target cells, it may be converted to dihydroxytestosterone (DHT) in some cell types. Testosterone and DHT bind to androgen receptors in the cytoplasm. The hormonereceptor complex enters the nucleus and binds a gene sequence called a hormone response element (HRE). Binding of the hormonereceptor complex to the HRE activates or inhibits gene expression.
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Figure 4: Simplified signal transduction pathway for testosterone. Testosterone enters the target cell and is converted to DHT. DHT binds with an intracellular hormone receptor to form a hormonereceptor complex that moves into the nucleus and binds to DNA to influence gene expression. © 2014 Nature Education All rights reserved.
For a long time, scientists thought that all steroid hormone receptors were intracellular. However, more recent studies have revealed the existence of cellsurface steroid receptors. For example, cell surface receptors for estradiol have been found. Binding of estradiol to cell surface receptors activates a signal transduction cascade that alters the activity of enzymes and modulates transcription. Cell surface receptors can elicit much more rapid responses than intracellular receptors. Both types of receptor may be present in the same cell, and the role of each receptor type in regulating cellular activity is an active area of research.
IN THIS MODULE
Intercellular Signaling Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Transmission of Hormonal Signals Signal Transduction by Steroid Hormones Summary Test Your Knowledge
WHY DOES THIS TOPIC MATTER?
Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cuttingedge research lead to prevention and treatment strategies that could make cancer obsolete?
PRIMARY LITERATURE
Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download
Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Singlechannel currents recorded from membrane of denervated frog muscle fibers. View | Download
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contents Principles of Biology
137 Hormones as Signaling Molecules
Signal Transduction by Steroid Hormones The drug tamoxifen has a chemical structure similar to estrogen and is able to bind the estrogen receptor and block estrogen binding. Some breast cancer cells depend on estrogen to grow and divide, and tamoxifen is commonly used to treat these types of cancers.
Betablocker drugs, which are frequently used to treat high blood pressure and arrhythmias (irregular heartbeats), are named for their ability to partially block the effect of epinephrine by interfering with the β2adrenergic receptor on cardiac and vascular smooth muscle cells.
IN THIS MODULE
Intercellular Signaling Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Transmission of Hormonal Signals Signal Transduction by Steroid Hormones Summary Test Your Knowledge
WHY DOES THIS TOPIC MATTER?
Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cuttingedge research lead to prevention and treatment strategies that could make cancer obsolete?
PRIMARY LITERATURE
Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download
Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Singlechannel currents recorded from membrane of denervated frog muscle fibers. View | Download
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contents Principles of Biology
137 Hormones as Signaling Molecules Summary
OBJECTIVE Compare the five types of intercellular signaling. There are five main types of intercellular signaling mechanisms. In autocrine signaling, a cell secretes a local regulator that acts on the secreting cell. In paracrine signaling, a cell secretes local regulators that act on cells in the immediate vicinity. In endocrine signaling, hormones are transported from the signaling cell to target cells via a circulatory system or other body fluid; the target cell can be very far from the signaling cell. In synaptic signaling, a neuron transmits a signal across an electrical synapse or a chemical synapse. In neuroendocrine signaling, a neuron releases neurohormones into the blood.
OBJECTIVE Explain how pheromones enable communication between individuals. Pheromones are chemical signals released into the environment for the purpose of communicating with other members of the same species. They may be used to communicate many messages to other individuals, including mating availability, a territorial claim, or a trail to or from a food source.
OBJECTIVE Describe how watersoluble and lipidsoluble hormones transmit signals. Because watersoluble hormones cannot freely cross the lipid bilayer of plasma membranes, they are secreted from endocrine cells by exocytosis. Once secreted, they diffuse through the bloodstream to reach their target cells. At the target cell, they bind to transmembrane receptors, which transmit the hormonal signal to intracellular signal transduction proteins. In turn, the intracellular proteins amplify the hormonal signal and produce physiological responses or changes in gene expression. Lipidsoluble hormones can freely cross the plasma membranes of both the endocrine cells that secreted them and their target cells but must be transported through the aqueous environment of the blood via specialized transport proteins. Many receptors for lipidsoluble hormones are intracellular. The intracellular hormone receptor complex is able to bind a hormone response element on DNA and alter gene expression. Extracellular lipid soluble hormone receptors activate a signal transduction cascade that alters the activity of enzymes and regulates transcription.
Key Terms
androgen A steroid that acts as a male sex hormone.
autocrine signaling A form of cell signaling in which the target cell is the same cell that originated the signal.
endocrine gland Organ of the endocrine system that releases hormones.
endocrine signaling A form of cell signaling in which a cell secretes signaling molecules (hormones) that travel through a circulatory system or other body fluid to act on distant target cells.
endocrine system Cells and glands in an animal that secrete hormones to communicate with distant cells via a circulatory system or other body fluid; work together with the nervous system to maintain homeostasis and respond to environmental changes.
epinephrine A hormone also known as adrenaline that is produced by the adrenal gland in response to acute stress; also secreted by some neurons as a neurotransmitter.
estradiol A steroid hormone that is synthesized from testosterone that can act as a female sex hormone.
estrogen A steroid that acts as a female sex hormone.
G proteincoupled receptor (GPCR) One of three major types of transmembrane receptors; uses G proteins as an intracellular signaling molecule.
hormone A chemical produced by glands or cells of the endocrine system that is transported in blood or hemolymph to distant target cells.
hormone response element (HRE) DNA sequence to which a steroid hormonereceptor complex binds.
local regulator A signal molecule that diffuses across the intracellular space to nearby targets; mediator of paracrine signaling.
neuroendocrine signaling A form of cell signaling in which a stimulated neuron releases signaling molecules (neurohormones) into the circulatory system or other body fluid.
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neurohormone A signaling molecule released from neurons directly into the body fluids; mediator of neuroendocrine signaling.
neurotransmitter A signaling molecule released from a presynaptic neuron that travels across the synaptic cleft and binds a receptor on the postsynaptic cell; mediator of synaptic signaling.
paracrine signaling A form of cell signaling in which signaling molecules called local regulators communicate with cells in the immediate vicinity.
pheromone A diffusible chemical signal released by an organism into the environment that elicits a response in another individual of the same species; can be used to communicate mating availability, territorial claims, directions to or from food sources, and so on.
receptor A protein to which a signaling molecule binds.
second messenger A small molecule or ion that mediates signaling between receptors at the plasma membrane and other signal transduction molecules in the cytoplasm or nucleus.
signal transduction The overall process by which cells respond to extracellular signaling molecules or other stimuli by executing a physiological response.
synapse A connection between a neuron and another cell.
synaptic signaling A form of cell communication in which neurons communicate to other cells (neurons or muscle cells) through a synapse.
testosterone Lipidsoluble androgen hormone that functions within the sexual reproductive system of vertebrates; promotes male sexual development and maturation.
IN THIS MODULE
Intercellular Signaling Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. Transmission of Hormonal Signals Signal Transduction by Steroid Hormones Summary Test Your Knowledge
WHY DOES THIS TOPIC MATTER?
Cancer: What's Old Is New Again Is cancer ancient, or is it largely a product of modern times? Can cuttingedge research lead to prevention and treatment strategies that could make cancer obsolete?
PRIMARY LITERATURE
Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk signaling protein by a proline switch. View | Download
Classic paper: Breakthrough enables tiny measurements of ion channel activity (1976) Singlechannel currents recorded from membrane of denervated frog muscle fibers. View | Download
page 702 of 989 1 pages left in this module
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contents Principles of Biology
137 Hormones as Signaling Molecules
IN THIS MODULE
Intercellular Signaling Test Your Knowledge Pheromones are Chemical Signals Transmitted Between Individuals of the Same Species. 1. An immune cell releases signaling molecules that bind receptors on nearby cells. What type of intercellular signaling is this? Transmission of Hormonal Signals Signal Transduction by Steroid Hormones paracrine Summary synaptic neuroendocrine Test Your Knowledge endocrine autocrine WHY DOES THIS TOPIC MATTER?
Cancer: What's Old Is New Again Is cancer ancient, or is it largely a 2. Which is the general purpose of pheromones? product of modern times? Can cuttingedge research lead to prevention They tell members of the opposite sex of mating opportunities. and treatment strategies that could make They allow organisms to signal to any other organism sharing the same habitat. cancer obsolete? They allow ants to follow trails to food sources. They mark territory and keep predators away. They let organisms communicate with others of their own species. PRIMARY LITERATURE Adaptor proteins regulate cell signaling Structural basis for regulation of the Crk 3. Which modes of chemical signaling rely on diffusible signaling molecules that work over relatively short signaling protein by a proline switch. distances? View | Download
paracrine and neuroendocrine signaling Classic paper: Breakthrough enables tiny measurements of ion endocrine and neuroendocrine signaling channel activity (1976) paracrine and autocrine signaling Singlechannel currents recorded from endocrine and autocrine signaling membrane of denervated frog muscle autocrine and neuroendocrine signaling fibers. View | Download
4. Which of the following statements about neuroendocrine and synaptic signaling are true?
Both neuroendocrine and synaptic signaling involve release of neurohormones that diffuse across synapses. In both neuroendocrine and synaptic signaling, neurotransmitters travel through the bloodstream. In synaptic signaling, neurotransmitters travel across the synapse, and in neuroendocrine signaling, neurohormones travel in the bloodstream. In both neuroendocrine and synaptic signaling the signaling molecule enters the target cell. Neurons are responsible for synaptic signaling, and endocrine cells are responsible for neuroendocrine signaling.
5. What is the main difference between pheromones and other types of chemical signals?
Most chemical signals remain within an organism; pheromones leave the organism and enter the environment to signal to others of the same species. Pheromones are released into synapses, while other signaling molecules are released into the bloodstream. Most chemical signals travel short distances between cells or directly to the cell that produced them. Pheromones travel long distances within the organism. Pheromones are used for sexual reproduction, while other chemical signals are not. Pheromones are released via exocytosis, while other chemical signals diffuse through the signaling cell's membrane.
6. A cell produces a lipidsoluble hormone. What molecule can help the hormone reach its target cell?
transport protein G proteincoupled receptors cytosolic receptor protein cAMP adenylyl cyclase
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