28.2 How Hormones Work

Learning Objectives

Learning Objectives

In this section, you will explore the following questions:

  • How do hormones work?
  • What is the role of different types of hormone receptors?

Connection for AP® Courses

Connection for AP® Courses

Much of the information in this section is an application of the material we explored in the Cell Communication chapter about cell communication and signaling pathways. Hormones are chemical signals—ligands—that mediate changes in target cells by binding to specific receptors. Even though hormones released by endocrine glands can travel long distances through the blood and come into contact with many different cell types, they only affect cells that possess the necessary receptors. Depending on the location of the receptor on the target cell and the chemical structure of the hormone, for example, whether or not it is lipid-soluble, hormones can mediate changes directly by binding to intracellular hormone receptors and modulating gene expression—transcription and translation—or indirectly by binding to cell surface receptors and simulating signaling pathways.

The hormone binds to its receptor like a key fits a lock. Because a lipid-derived hormone such as a steroid hormone can diffuse across the membrane of the target cell, they bind to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by steroid hormones regulate specific genes by acting as transcription regulators. In turn, this affects the amount of protein produced. Lipid-derived hormones that are not steroids, for example, vitamin D and thyroxin, bind to receptors located in the nucleus of the target cell.

Because amino acid-derived hormones and polypeptide hormones are not lipid-soluble, they bind to plasma membrane hormone receptors located on the outer surface of the membrane. Unlike steroid hormones, they cannot act directly on DNA but activate a signaling pathway; this triggers intracellular activity and carries out the specific effects associated with the hormone. The hormone that initiated the signaling pathway is called a first messenger. In the case of the epinephrine signaling pathway, binding of the amino acid-derived hormone epinephrine to its receptor activates a G-protein that, in turn, activates cAMP, a second messenger, ultimately resulting in a cellular response such as the conversion of glycogen to glucose.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP® Biology Curriculum Framework. The AP® Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A learning objective merges required content with one or more of the seven science practices.

Big Idea 3 Living systems store, retrieve, transmit, and respond to information essential to life processes.
Enduring Understanding 3.D Cells communicate by generating, transmitting, and receiving chemical signals.
Essential Knowledge 3.D.3 Signal transduction pathways link signal reception with a cellular response.
Science Practice 1.5 The student can re-express key elements of natural phenomena across multiple representations in the domain.
Learning Objective 3.36 The student is able to describe a model that expresses the key elements of signal transduction pathways by which a signal is converted in to a cellular response.

Hormones mediate changes in target cells by binding to specific hormone receptors. 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’s 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 up-regulation, 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, a process called down-regulation, cellular activity is reduced.

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 intracellular hormone receptors and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.

Intracellular Hormone Receptors

Intracellular Hormone Receptors

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 28.5.

Visual Connection

Illustration shows a hormone crossing the cellular membrane and attaching to the NR/HSP complex. The complex dissociates, releasing the heat shock protein and a NR/hormone complex. The complex dimerizes, enters the nucleus, and attaches to an HRE element on DNA, triggering transcription of certain genes.
Figure 28.5 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.

Heat shock proteins (HSP) are so named because they help refold misfolded proteins. In response to increased temperature (a heat shock), heat shock proteins are activated by release from the nuclear receptor/HSP complex. At the same time, transcription of HSP genes is activated. Explain the role of heat shock in refolding misfolded proteins.

  1. Heat is a stimulus that prevents hormone binding.
  2. Heat is a stimulus that facilitates hormone binding.
  3. Heat is a stimulus that facilitates dissociation of receptor from HSP directly.
  4. Heat is a stimulus that facilitates binding of a hormone-receptor complex to a hormone response element.

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.

Plasma Membrane Hormone Receptors

Plasma Membrane Hormone Receptors

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 plasma membrane hormone receptors. 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 first messenger, which activates a second messenger in the cytoplasm, as illustrated in Figure 28.6.

Illustration shows epinephrine bound to the extracellular surface of a beta-adrenergic receptor. A G-protein associated with the intracellular surface of the receptor is activated when the GDP associated with it is replaced with GTP. The G protein activates the enzyme adenylyl cyclase, which converts ATP to cAMP, triggering a cellular response.
Figure 28.6 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 into cAMP. cAMP is a second messenger that mediates a cell-specific response. An enzyme called phosphodiesterase breaks down cAMP, terminating the signal.

One very important second messenger is cyclic AMP (cAMP). When a hormone binds to its membrane receptor, a G-protein 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.

The activated G-protein in turn activates a membrane-bound enzyme called adenylyl cyclase. 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.

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 phosphodiesterase, or PDE. PDE is always present in the cell and breaks down cAMP to control hormone activity, preventing overproduction of cellular products.

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.

Science Practice Connection for AP® Courses

Activity

Create a representation to describe how a lipid-soluble hormone and a peptide hormone activate different cellular responses in a target cell.