{"id":4933,"date":"2015-10-28T15:56:07","date_gmt":"2015-10-28T15:56:07","guid":{"rendered":"https:\/\/opentextbc.ca\/biology\/chapter\/18-2-how-hormones-work\/"},"modified":"2021-03-04T00:07:59","modified_gmt":"2021-03-04T00:07:59","slug":"18-2-how-hormones-work","status":"publish","type":"chapter","link":"https:\/\/opentextbc.ca\/biology\/chapter\/18-2-how-hormones-work\/","title":{"raw":"18.2 How Hormones Work","rendered":"18.2 How Hormones Work"},"content":{"raw":"<div class=\"section module\" title=\"37.2.\u00a0How Hormones Work\" xml:lang=\"en\">\n<div class=\"titlepage\">\n<div class=\"abstract\">\n<div class=\"bcc-box bcc-highlight\">\n<h3>Learning Objectives<\/h3>\nBy the end of this section, you will be able to:\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n \t<li class=\"listitem\">Explain how hormones work<\/li>\n \t<li class=\"listitem\">Discuss the role of different types of hormone receptors<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<span id=\"m44768-fs-idp268044016\"> <\/span>Hormones mediate changes in target cells by binding to specific <span id=\"m44768-autoid-cnx2dbk-id1829899\"> <\/span><strong>hormone <span id=\"m44768-autoid-cnx2dbk-id1829903\"> <\/span>receptors<\/strong>. In this way, even though hormones circulate throughout the body and come into contact with many different cell types, they only affect cells that possess the necessary receptors. Receptors for a specific hormone may be found on many different cells or may be limited to a small number of specialized cells. For example, thyroid hormones act on many different tissue types, stimulating metabolic activity throughout the body. Cells can have many receptors for the same hormone but often also possess receptors for different types of hormones. The number of receptors that respond to a hormone determines the cell\u2019s sensitivity to that hormone, and the resulting cellular response. Additionally, the number of receptors that respond to a hormone can change over time, resulting in increased or decreased cell sensitivity. In <span id=\"m44768-autoid-cnx2dbk-id1829914\"> <\/span><strong>up-regulation<\/strong>, the number of receptors increases in response to rising hormone levels, making the cell more sensitive to the hormone and allowing for more cellular activity. When the number of receptors decreases in response to rising hormone levels, called <span id=\"m44768-autoid-cnx2dbk-id1829920\"> <\/span><strong>down-regulation<\/strong>, cellular activity is reduced.\n\n<span id=\"m44768-fs-idp39453248\"> <\/span>Receptor binding alters cellular activity and results in an increase or decrease in normal body processes. Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to <span id=\"m44768-autoid-cnx2dbk-id1829931\"> <\/span><strong>intracellular hormone receptors<\/strong> and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.\n<div class=\"section\" title=\"Intracellular Hormone Receptors\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44768-fs-idm6952064\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Intracellular Hormone Receptors<\/span><\/span><\/h2>\n<\/div>\n<\/div>\n<\/div>\n<span id=\"m44768-fs-idp39011552\"> <\/span>Lipid-derived (soluble) hormones such as steroid hormones diffuse across the membranes of the endocrine cell. Once outside the cell, they bind to transport proteins that keep them soluble in the bloodstream. At the target cell, the hormones are released from the carrier protein and diffuse across the lipid bilayer of the plasma membrane of cells. The steroid hormones pass through the plasma membrane of a target cell and adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by the steroid hormones regulate specific genes on the cell's DNA. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules of specific genes. This, in turn, determines the amount of corresponding protein that is synthesized by altering gene expression. This protein can be used either to change the structure of the cell or to produce enzymes that catalyze chemical reactions. In this way, the steroid hormone regulates specific cell processes as illustrated in Figure 18.5.\n\n<\/div>\n<div id=\"m44768-fs-idp99897760\" class=\"note art-connection\">\n<div class=\"title\">\n\n[caption id=\"attachment_1220\" align=\"aligncenter\" width=\"500\"]<a href=\"http:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/03\/Figure_37_02_01.png\"><img class=\"wp-image-4931\" src=\"https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1.png\" alt=\"Figure_37_02_01\" width=\"500\" height=\"300\"><\/a> Figure 18.5.\u00a0 An intracellular nuclear receptor (NR) is located in the cytoplasm bound to a heat shock protein (HSP). Upon hormone binding, the receptor dissociates from the heat shock protein and translocates to the nucleus. In the nucleus, the hormone-receptor complex binds to a DNA sequence called a hormone response element (HRE), which triggers gene transcription and translation. The corresponding protein product can then mediate changes in cell function.[\/caption]\n\n<\/div>\n<div class=\"body\">\n<div id=\"m44768-fig-ch37_02_01\" class=\"figure\" title=\"Figure\u00a037.5.\u00a0\">\n<div class=\"body\">\n\n<span id=\"m44768-fs-idp80895504\"> <\/span>Heat shock proteins (HSP) are so named because they help refold misfolded proteins. In response to increased temperature (a \u201cheat shock\u201d), heat shock proteins are activated by release from the NR\/HSP complex. At the same time, transcription of HSP genes is activated. Why do you think the cell responds to a heat shock by increasing the activity of proteins that help refold misfolded proteins?\n\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<span id=\"m44768-fs-idp135634080\"> <\/span>Other lipid-soluble hormones that are not steroid hormones, such as vitamin D and thyroxine, have receptors located in the nucleus. The hormones diffuse across both the plasma membrane and the nuclear envelope, then bind to receptors in the nucleus. The hormone-receptor complex stimulates transcription of specific genes.\n\n<\/div>\n<div class=\"section\" title=\"Plasma Membrane Hormone Receptors\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44768-fs-idp117931792\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Plasma Membrane Hormone Receptors<\/span><\/span><\/h2>\n<\/div>\n<\/div>\n<\/div>\n<span id=\"m44768-fs-idp78427184\"> <\/span>Amino acid derived hormones and polypeptide hormones are not lipid-derived (lipid-soluble) and therefore cannot diffuse through the plasma membrane of cells. Lipid insoluble hormones bind to receptors on the outer surface of the plasma membrane, via <span id=\"m44768-autoid-cnx2dbk-id1826274\"> <\/span><strong>plasma membrane hormone receptors<\/strong>. Unlike steroid hormones, lipid insoluble hormones do not directly affect the target cell because they cannot enter the cell and act directly on DNA. Binding of these hormones to a cell surface receptor results in activation of a signaling pathway; this triggers intracellular activity and carries out the specific effects associated with the hormone. In this way, nothing passes through the cell membrane; the hormone that binds at the surface remains at the surface of the cell while the intracellular product remains inside the cell. The hormone that initiates the signaling pathway is called a <strong><span id=\"m44768-autoid-cnx2dbk-id1826282\"> <\/span>first messenger<\/strong>, which activates a second messenger in the cytoplasm, as illustrated in Figure 18.6.\n\n[caption id=\"attachment_1221\" align=\"aligncenter\" width=\"600\"]<a href=\"http:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/03\/Figure_37_02_02.jpg\"><img class=\"wp-image-4932\" src=\"https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1.jpg\" alt=\"Figure_37_02_02\" width=\"600\" height=\"369\"><\/a> Figure 18.6.\u00a0 The amino acid-derived hormones epinephrine and norepinephrine bind to beta-adrenergic receptors on the plasma membrane of cells. Hormone binding to receptor activates a G-protein, which in turn activates adenylyl cyclase, converting ATP to cAMP. cAMP is a second messenger that mediates a cell-specific response. An enzyme called phosphodiesterase breaks down cAMP, terminating the signal.[\/caption]\n\n<div id=\"m44768-fig-ch37_02_02\" class=\"figure\" title=\"Figure\u00a037.6.\u00a0\">\n\n<span id=\"m44768-fs-idp53679792\"> <\/span>One very important second messenger is cyclic AMP (cAMP). When a hormone binds to its membrane receptor, a <span id=\"m44768-autoid-cnx2dbk-id1823006\"> <\/span><strong>G-protein<\/strong> that is associated with the receptor is activated; G-proteins are proteins separate from receptors that are found in the cell membrane. When a hormone is not bound to the receptor, the G-protein is inactive and is bound to guanosine diphosphate, or GDP. When a hormone binds to the receptor, the G-protein is activated by binding guanosine triphosphate, or GTP, in place of GDP. After binding, GTP is hydrolysed by the G-protein into GDP and becomes inactive.\n\n<span id=\"m44768-fs-idp260294208\"> <\/span>The activated G-protein in turn activates a membrane-bound enzyme called <strong><span id=\"m44768-autoid-cnx2dbk-id1823018\"> <\/span>adenylyl cyclase<\/strong>. Adenylyl cyclase catalyzes the conversion of ATP to cAMP. cAMP, in turn, activates a group of proteins called protein kinases, which transfer a phosphate group from ATP to a substrate molecule in a process called phosphorylation. The phosphorylation of a substrate molecule changes its structural orientation, thereby activating it. These activated molecules can then mediate changes in cellular processes.\n\n<span id=\"m44768-fs-idp54512752\"> <\/span>The effect of a hormone is amplified as the signaling pathway progresses. The binding of a hormone at a single receptor causes the activation of many G-proteins, which activates adenylyl cyclase. Each molecule of adenylyl cyclase then triggers the formation of many molecules of cAMP. Further amplification occurs as protein kinases, once activated by cAMP, can catalyze many reactions. In this way, a small amount of hormone can trigger the formation of a large amount of cellular product. To stop hormone activity, cAMP is deactivated by the cytoplasmic enzyme <span id=\"m44768-autoid-cnx2dbk-id1823036\"> <\/span><strong>phosphodiesterase<\/strong>, or PDE. PDE is always present in the cell and breaks down cAMP to control hormone activity, preventing overproduction of cellular products.\n\n<span id=\"m44768-fs-idp174337632\"> <\/span>The specific response of a cell to a lipid insoluble hormone depends on the type of receptors that are present on the cell membrane and the substrate molecules present in the cell cytoplasm. Cellular responses to hormone binding of a receptor include altering membrane permeability and metabolic pathways, stimulating synthesis of proteins and enzymes, and activating hormone release.\n<h2>Summary<\/h2>\nHormones cause cellular changes by binding to receptors on target cells. The number of receptors on a target cell can increase or decrease in response to hormone activity. Hormones can affect cells directly through intracellular hormone receptors or indirectly through plasma membrane hormone receptors.\n\n<span id=\"m44768-fs-idp169369024\"> <\/span>Lipid-derived (soluble) hormones can enter the cell by diffusing across the plasma membrane and binding to DNA to regulate gene transcription and to change the cell\u2019s activities by inducing production of proteins that affect, in general, the long-term structure and function of the cell. Lipid insoluble hormones bind to receptors on the plasma membrane surface and trigger a signaling pathway to change the cell\u2019s activities by inducing production of various cell products that affect the cell in the short-term. The hormone is called a first messenger and the cellular component is called a second messenger. G-proteins activate the second messenger (cyclic AMP), triggering the cellular response. Response to hormone binding is amplified as the signaling pathway progresses. Cellular responses to hormones include the production of proteins and enzymes and altered membrane permeability.\n<div class=\"textbox exercises\">\n<h3>Exercises<\/h3>\n<ol>\n \t<li>A new antagonist molecule has been discovered that binds to and blocks plasma membrane receptors. What effect will this antagonist have on testosterone, a steroid hormone?\n<ol>\n \t<li>It will block testosterone from binding to its receptor.<\/li>\n \t<li>It will block testosterone from activating cAMP signaling.<\/li>\n \t<li>It will increase testosterone-mediated signaling.<\/li>\n \t<li>It will not affect testosterone-mediated signaling.<\/li>\n<\/ol>\n<\/li>\n \t<li><span id=\"m44768-fs-idp164952160\">What effect will a cAMP inhibitor have on a peptide hormone-mediated signaling pathway?<\/span>\n<ol>\n \t<li>It will prevent the hormone from binding its receptor.<\/li>\n \t<li>It will prevent activation of a G-protein.<\/li>\n \t<li>It will prevent activation of adenylate cyclase.<\/li>\n \t<li>It will prevent activation of protein kinases.<\/li>\n<\/ol>\n<\/li>\n \t<li>Name two important functions of hormone receptors.<\/li>\n \t<li>How can hormones mediate changes?<\/li>\n<\/ol>\n<strong>Answers<\/strong>\n<ol>\n \t<li>D<\/li>\n \t<li>D<\/li>\n \t<li>The number of receptors that respond to a hormone can change, resulting in increased or decreased cell sensitivity. The number of receptors can increase in response to rising hormone levels, called up-regulation, making the cell more sensitive to the hormone and allowing for more cellular activity. The number of receptors can also decrease in response to rising hormone levels, called down-regulation, leading to reduced cellular activity.<\/li>\n \t<li>Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to intracellular receptors and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.<\/li>\n<\/ol>\n<\/div>\n<div class=\"section module\" title=\"37.5.\u00a0Endocrine Glands\" xml:lang=\"en\">\n<div class=\"section\" title=\"Organs with Secondary Endocrine Functions\">\n<div class=\"cnx-eoc summary\">\n<div class=\"section\">\n<div class=\"title\">\n<div class=\"body\">\n<div class=\"exercise\">\n<div class=\"title\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"glossary\" title=\"Glossary\">\n<div class=\"titlepage\">\n<div class=\"bcc-box bcc-success\">\n<h3>Glossary<\/h3>\n<dl>\n \t<dt><strong>adenylate cyclase<\/strong><\/dt>\n \t<dd>an enzyme that catalyzes the conversion of ATP to cyclic AMP<\/dd>\n \t<dt><strong>down-regulation<\/strong><\/dt>\n \t<dd>a decrease in the number of hormone receptors in response to increased hormone levels<\/dd>\n \t<dt><strong>first messenger<\/strong><\/dt>\n \t<dd>the hormone that binds to a plasma membrane hormone receptor to trigger a signal transduction pathway<\/dd>\n \t<dt><strong>G-protein<\/strong><\/dt>\n \t<dd>a membrane protein activated by the hormone first messenger to activate formation of cyclic AMP<\/dd>\n \t<dt><strong>hormone receptor<\/strong><\/dt>\n \t<dd>the cellular protein that binds to a hormone<\/dd>\n \t<dt><strong>intracellular hormone receptor<\/strong><\/dt>\n \t<dd>a hormone receptor in the cytoplasm or nucleus of a cell<\/dd>\n \t<dt><strong>phosphodiesterase (PDE)<\/strong><\/dt>\n \t<dd>enzyme that deactivates cAMP, stopping hormone activity<\/dd>\n \t<dt><strong>plasma membrane hormone receptor<\/strong><\/dt>\n \t<dd>a hormone receptor on the surface of the plasma membrane of a cell<\/dd>\n \t<dt><strong>up-regulation<\/strong><\/dt>\n \t<dd>an increase in the number of hormone receptors in response to increased hormone levels<\/dd>\n<\/dl>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"cnx-eoc summary\">\n<div class=\"section\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n&nbsp;\n\n<\/div>\n<\/div>","rendered":"<div class=\"section module\" title=\"37.2.\u00a0How Hormones Work\" xml:lang=\"en\">\n<div class=\"titlepage\">\n<div class=\"abstract\">\n<div class=\"bcc-box bcc-highlight\">\n<h3>Learning Objectives<\/h3>\n<p>By the end of this section, you will be able to:<\/p>\n<div class=\"itemizedlist\">\n<ul class=\"itemizedlist\">\n<li class=\"listitem\">Explain how hormones work<\/li>\n<li class=\"listitem\">Discuss the role of different types of hormone receptors<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44768-fs-idp268044016\"> <\/span>Hormones mediate changes in target cells by binding to specific <span id=\"m44768-autoid-cnx2dbk-id1829899\"> <\/span><strong>hormone <span id=\"m44768-autoid-cnx2dbk-id1829903\"> <\/span>receptors<\/strong>. In this way, even though hormones circulate throughout the body and come into contact with many different cell types, they only affect cells that possess the necessary receptors. Receptors for a specific hormone may be found on many different cells or may be limited to a small number of specialized cells. For example, thyroid hormones act on many different tissue types, stimulating metabolic activity throughout the body. Cells can have many receptors for the same hormone but often also possess receptors for different types of hormones. The number of receptors that respond to a hormone determines the cell\u2019s sensitivity to that hormone, and the resulting cellular response. Additionally, the number of receptors that respond to a hormone can change over time, resulting in increased or decreased cell sensitivity. In <span id=\"m44768-autoid-cnx2dbk-id1829914\"> <\/span><strong>up-regulation<\/strong>, the number of receptors increases in response to rising hormone levels, making the cell more sensitive to the hormone and allowing for more cellular activity. When the number of receptors decreases in response to rising hormone levels, called <span id=\"m44768-autoid-cnx2dbk-id1829920\"> <\/span><strong>down-regulation<\/strong>, cellular activity is reduced.<\/p>\n<p><span id=\"m44768-fs-idp39453248\"> <\/span>Receptor binding alters cellular activity and results in an increase or decrease in normal body processes. Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to <span id=\"m44768-autoid-cnx2dbk-id1829931\"> <\/span><strong>intracellular hormone receptors<\/strong> and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.<\/p>\n<div class=\"section\" title=\"Intracellular Hormone Receptors\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44768-fs-idm6952064\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Intracellular Hormone Receptors<\/span><\/span><\/h2>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44768-fs-idp39011552\"> <\/span>Lipid-derived (soluble) hormones such as steroid hormones diffuse across the membranes of the endocrine cell. Once outside the cell, they bind to transport proteins that keep them soluble in the bloodstream. At the target cell, the hormones are released from the carrier protein and diffuse across the lipid bilayer of the plasma membrane of cells. The steroid hormones pass through the plasma membrane of a target cell and adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by the steroid hormones regulate specific genes on the cell&#8217;s DNA. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules of specific genes. This, in turn, determines the amount of corresponding protein that is synthesized by altering gene expression. This protein can be used either to change the structure of the cell or to produce enzymes that catalyze chemical reactions. In this way, the steroid hormone regulates specific cell processes as illustrated in Figure 18.5.<\/p>\n<\/div>\n<div id=\"m44768-fs-idp99897760\" class=\"note art-connection\">\n<div class=\"title\">\n<figure id=\"attachment_1220\" aria-describedby=\"caption-attachment-1220\" style=\"width: 500px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/03\/Figure_37_02_01.png\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4931\" src=\"https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1.png\" alt=\"Figure_37_02_01\" width=\"500\" height=\"300\" srcset=\"https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1.png 1024w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1-300x180.png 300w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1-768x461.png 768w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1-65x39.png 65w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1-225x135.png 225w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/10\/Figure_37_02_01-1024x615-1-350x210.png 350w\" sizes=\"auto, (max-width: 500px) 100vw, 500px\" \/><\/a><figcaption id=\"caption-attachment-1220\" class=\"wp-caption-text\">Figure 18.5.\u00a0 An intracellular nuclear receptor (NR) is located in the cytoplasm bound to a heat shock protein (HSP). Upon hormone binding, the receptor dissociates from the heat shock protein and translocates to the nucleus. In the nucleus, the hormone-receptor complex binds to a DNA sequence called a hormone response element (HRE), which triggers gene transcription and translation. The corresponding protein product can then mediate changes in cell function.<\/figcaption><\/figure>\n<\/div>\n<div class=\"body\">\n<div id=\"m44768-fig-ch37_02_01\" class=\"figure\" title=\"Figure\u00a037.5.\u00a0\">\n<div class=\"body\">\n<p><span id=\"m44768-fs-idp80895504\"> <\/span>Heat shock proteins (HSP) are so named because they help refold misfolded proteins. In response to increased temperature (a \u201cheat shock\u201d), heat shock proteins are activated by release from the NR\/HSP complex. At the same time, transcription of HSP genes is activated. Why do you think the cell responds to a heat shock by increasing the activity of proteins that help refold misfolded proteins?<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44768-fs-idp135634080\"> <\/span>Other lipid-soluble hormones that are not steroid hormones, such as vitamin D and thyroxine, have receptors located in the nucleus. The hormones diffuse across both the plasma membrane and the nuclear envelope, then bind to receptors in the nucleus. The hormone-receptor complex stimulates transcription of specific genes.<\/p>\n<\/div>\n<div class=\"section\" title=\"Plasma Membrane Hormone Receptors\">\n<div class=\"titlepage\">\n<div>\n<div>\n<h2 id=\"m44768-fs-idp117931792\"><span class=\"cnx-gentext-section cnx-gentext-autogenerated\"><span class=\"cnx-gentext-section cnx-gentext-t\">Plasma Membrane Hormone Receptors<\/span><\/span><\/h2>\n<\/div>\n<\/div>\n<\/div>\n<p><span id=\"m44768-fs-idp78427184\"> <\/span>Amino acid derived hormones and polypeptide hormones are not lipid-derived (lipid-soluble) and therefore cannot diffuse through the plasma membrane of cells. Lipid insoluble hormones bind to receptors on the outer surface of the plasma membrane, via <span id=\"m44768-autoid-cnx2dbk-id1826274\"> <\/span><strong>plasma membrane hormone receptors<\/strong>. Unlike steroid hormones, lipid insoluble hormones do not directly affect the target cell because they cannot enter the cell and act directly on DNA. Binding of these hormones to a cell surface receptor results in activation of a signaling pathway; this triggers intracellular activity and carries out the specific effects associated with the hormone. In this way, nothing passes through the cell membrane; the hormone that binds at the surface remains at the surface of the cell while the intracellular product remains inside the cell. The hormone that initiates the signaling pathway is called a <strong><span id=\"m44768-autoid-cnx2dbk-id1826282\"> <\/span>first messenger<\/strong>, which activates a second messenger in the cytoplasm, as illustrated in Figure 18.6.<\/p>\n<figure id=\"attachment_1221\" aria-describedby=\"caption-attachment-1221\" style=\"width: 600px\" class=\"wp-caption aligncenter\"><a href=\"http:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2015\/03\/Figure_37_02_02.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4932\" src=\"https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1.jpg\" alt=\"Figure_37_02_02\" width=\"600\" height=\"369\" srcset=\"https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1.jpg 1024w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1-300x184.jpg 300w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1-768x472.jpg 768w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1-65x40.jpg 65w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1-225x138.jpg 225w, https:\/\/opentextbc.ca\/biology\/wp-content\/uploads\/sites\/96\/2021\/03\/Figure_37_02_02-1024x629-1-350x215.jpg 350w\" sizes=\"auto, (max-width: 600px) 100vw, 600px\" \/><\/a><figcaption id=\"caption-attachment-1221\" class=\"wp-caption-text\">Figure 18.6.\u00a0 The amino acid-derived hormones epinephrine and norepinephrine bind to beta-adrenergic receptors on the plasma membrane of cells. Hormone binding to receptor activates a G-protein, which in turn activates adenylyl cyclase, converting ATP to cAMP. cAMP is a second messenger that mediates a cell-specific response. An enzyme called phosphodiesterase breaks down cAMP, terminating the signal.<\/figcaption><\/figure>\n<div id=\"m44768-fig-ch37_02_02\" class=\"figure\" title=\"Figure\u00a037.6.\u00a0\">\n<p><span id=\"m44768-fs-idp53679792\"> <\/span>One very important second messenger is cyclic AMP (cAMP). When a hormone binds to its membrane receptor, a <span id=\"m44768-autoid-cnx2dbk-id1823006\"> <\/span><strong>G-protein<\/strong> that is associated with the receptor is activated; G-proteins are proteins separate from receptors that are found in the cell membrane. When a hormone is not bound to the receptor, the G-protein is inactive and is bound to guanosine diphosphate, or GDP. When a hormone binds to the receptor, the G-protein is activated by binding guanosine triphosphate, or GTP, in place of GDP. After binding, GTP is hydrolysed by the G-protein into GDP and becomes inactive.<\/p>\n<p><span id=\"m44768-fs-idp260294208\"> <\/span>The activated G-protein in turn activates a membrane-bound enzyme called <strong><span id=\"m44768-autoid-cnx2dbk-id1823018\"> <\/span>adenylyl cyclase<\/strong>. Adenylyl cyclase catalyzes the conversion of ATP to cAMP. cAMP, in turn, activates a group of proteins called protein kinases, which transfer a phosphate group from ATP to a substrate molecule in a process called phosphorylation. The phosphorylation of a substrate molecule changes its structural orientation, thereby activating it. These activated molecules can then mediate changes in cellular processes.<\/p>\n<p><span id=\"m44768-fs-idp54512752\"> <\/span>The effect of a hormone is amplified as the signaling pathway progresses. The binding of a hormone at a single receptor causes the activation of many G-proteins, which activates adenylyl cyclase. Each molecule of adenylyl cyclase then triggers the formation of many molecules of cAMP. Further amplification occurs as protein kinases, once activated by cAMP, can catalyze many reactions. In this way, a small amount of hormone can trigger the formation of a large amount of cellular product. To stop hormone activity, cAMP is deactivated by the cytoplasmic enzyme <span id=\"m44768-autoid-cnx2dbk-id1823036\"> <\/span><strong>phosphodiesterase<\/strong>, or PDE. PDE is always present in the cell and breaks down cAMP to control hormone activity, preventing overproduction of cellular products.<\/p>\n<p><span id=\"m44768-fs-idp174337632\"> <\/span>The specific response of a cell to a lipid insoluble hormone depends on the type of receptors that are present on the cell membrane and the substrate molecules present in the cell cytoplasm. Cellular responses to hormone binding of a receptor include altering membrane permeability and metabolic pathways, stimulating synthesis of proteins and enzymes, and activating hormone release.<\/p>\n<h2>Summary<\/h2>\n<p>Hormones cause cellular changes by binding to receptors on target cells. The number of receptors on a target cell can increase or decrease in response to hormone activity. Hormones can affect cells directly through intracellular hormone receptors or indirectly through plasma membrane hormone receptors.<\/p>\n<p><span id=\"m44768-fs-idp169369024\"> <\/span>Lipid-derived (soluble) hormones can enter the cell by diffusing across the plasma membrane and binding to DNA to regulate gene transcription and to change the cell\u2019s activities by inducing production of proteins that affect, in general, the long-term structure and function of the cell. Lipid insoluble hormones bind to receptors on the plasma membrane surface and trigger a signaling pathway to change the cell\u2019s activities by inducing production of various cell products that affect the cell in the short-term. The hormone is called a first messenger and the cellular component is called a second messenger. G-proteins activate the second messenger (cyclic AMP), triggering the cellular response. Response to hormone binding is amplified as the signaling pathway progresses. Cellular responses to hormones include the production of proteins and enzymes and altered membrane permeability.<\/p>\n<div class=\"textbox exercises\">\n<h3>Exercises<\/h3>\n<ol>\n<li>A new antagonist molecule has been discovered that binds to and blocks plasma membrane receptors. What effect will this antagonist have on testosterone, a steroid hormone?\n<ol>\n<li>It will block testosterone from binding to its receptor.<\/li>\n<li>It will block testosterone from activating cAMP signaling.<\/li>\n<li>It will increase testosterone-mediated signaling.<\/li>\n<li>It will not affect testosterone-mediated signaling.<\/li>\n<\/ol>\n<\/li>\n<li><span id=\"m44768-fs-idp164952160\">What effect will a cAMP inhibitor have on a peptide hormone-mediated signaling pathway?<\/span>\n<ol>\n<li>It will prevent the hormone from binding its receptor.<\/li>\n<li>It will prevent activation of a G-protein.<\/li>\n<li>It will prevent activation of adenylate cyclase.<\/li>\n<li>It will prevent activation of protein kinases.<\/li>\n<\/ol>\n<\/li>\n<li>Name two important functions of hormone receptors.<\/li>\n<li>How can hormones mediate changes?<\/li>\n<\/ol>\n<p><strong>Answers<\/strong><\/p>\n<ol>\n<li>D<\/li>\n<li>D<\/li>\n<li>The number of receptors that respond to a hormone can change, resulting in increased or decreased cell sensitivity. The number of receptors can increase in response to rising hormone levels, called up-regulation, making the cell more sensitive to the hormone and allowing for more cellular activity. The number of receptors can also decrease in response to rising hormone levels, called down-regulation, leading to reduced cellular activity.<\/li>\n<li>Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to intracellular receptors and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.<\/li>\n<\/ol>\n<\/div>\n<div class=\"section module\" title=\"37.5.\u00a0Endocrine Glands\" xml:lang=\"en\">\n<div class=\"section\" title=\"Organs with Secondary Endocrine Functions\">\n<div class=\"cnx-eoc summary\">\n<div class=\"section\">\n<div class=\"title\">\n<div class=\"body\">\n<div class=\"exercise\">\n<div class=\"title\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"glossary\" title=\"Glossary\">\n<div class=\"titlepage\">\n<div class=\"bcc-box bcc-success\">\n<h3>Glossary<\/h3>\n<dl>\n<dt><strong>adenylate cyclase<\/strong><\/dt>\n<dd>an enzyme that catalyzes the conversion of ATP to cyclic AMP<\/dd>\n<dt><strong>down-regulation<\/strong><\/dt>\n<dd>a decrease in the number of hormone receptors in response to increased hormone levels<\/dd>\n<dt><strong>first messenger<\/strong><\/dt>\n<dd>the hormone that binds to a plasma membrane hormone receptor to trigger a signal transduction pathway<\/dd>\n<dt><strong>G-protein<\/strong><\/dt>\n<dd>a membrane protein activated by the hormone first messenger to activate formation of cyclic AMP<\/dd>\n<dt><strong>hormone receptor<\/strong><\/dt>\n<dd>the cellular protein that binds to a hormone<\/dd>\n<dt><strong>intracellular hormone receptor<\/strong><\/dt>\n<dd>a hormone receptor in the cytoplasm or nucleus of a cell<\/dd>\n<dt><strong>phosphodiesterase (PDE)<\/strong><\/dt>\n<dd>enzyme that deactivates cAMP, stopping hormone activity<\/dd>\n<dt><strong>plasma membrane hormone receptor<\/strong><\/dt>\n<dd>a hormone receptor on the surface of the plasma membrane of a cell<\/dd>\n<dt><strong>up-regulation<\/strong><\/dt>\n<dd>an increase in the number of hormone receptors in response to increased hormone levels<\/dd>\n<\/dl>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"cnx-eoc summary\">\n<div class=\"section\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n","protected":false},"author":90,"menu_order":40,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":"cc-by"},"chapter-type":[],"contributor":[],"license":[57],"class_list":["post-4933","chapter","type-chapter","status-publish","hentry","license-cc-by"],"part":4924,"_links":{"self":[{"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/chapters\/4933","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/wp\/v2\/users\/90"}],"version-history":[{"count":1,"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/chapters\/4933\/revisions"}],"predecessor-version":[{"id":4934,"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/chapters\/4933\/revisions\/4934"}],"part":[{"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/parts\/4924"}],"metadata":[{"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/chapters\/4933\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/wp\/v2\/media?parent=4933"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/pressbooks\/v2\/chapter-type?post=4933"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/wp\/v2\/contributor?post=4933"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/opentextbc.ca\/biology\/wp-json\/wp\/v2\/license?post=4933"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}