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BioFlix: Mechanism of Hormone Action: Second Messenger cAMP

by Pearson
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The endocrine system consists of hormone-producing tissues located throughout the body. The circulating hormones control the rates of body processes and maintain homeostasis. Within an endocrine gland endocrine cells secrete hormones which diffuse into nearby capillaries. The cardiovascular system transports these hormones throughout the body, affecting target cells in various tissues. Target cells for a specific hormone have receptors that bind the unique three-dimensional shape of that hormone. Cells that lack a specific hormone receptor are unresponsive to that hormone, even if a high concentration of the hormone is present around the cells. Although cells express a variety of receptors, we'll focus on one particular class: receptors that bind water-soluble hormones and exert their effects through the intracellular second messenger cyclic AMP. These receptors are embedded in the cell's plasma membrane, because water-soluble hormones cannot enter the target cell directly. A hormone molecule, acting as the first messenger, binds to its receptor, causing the receptor to change shape. The receptor can now activate specific intracellular G proteins. The activation process begins with the release of a GDP molecule from the G protein in exchange for a GTP molecule. This causes the G protein to change shape and become active. The hormone-bound receptor activates many individual G proteins, which greatly amplifies the signal from a single hormone molecule. An activated G protein diffuses along the plasma membrane until it binds to, and activates, the enzyme adenylate cyclase. Once active, adenylate cyclase converts ATP to the second messenger cyclic AMP. These many molecules of cyclic AMP, from each activated cyclase enzyme, represent a further amplification of the initial hormone signal. The increased concentration of cyclic AMP activates enzymes known as protein kinases. These activated protein kinases phosphorylate a variety of proteins within the cell. This changes the activity of those proteins and generates the cell's hormone response. The cell's response is characterized by the specific proteins present in the cytoplasm, only some of which can be phosphorylated by protein kinase. The cellular response diminishes rapidly once the hormone is no longer bound to its receptor. G proteins hydrolyze their bound GTP to GDP, returning to their inactive state, and dissociate from adenylate cyclase. This ends cyclic AMP production. Existing cyclic AMP is degraded by the enzyme phosphodiesterase, which is already present in the cyctoplasm. As the cyclic AMP concentration returns to resting levels, protein kinase inactivates, preventing further protein phosphorylation. The target cell has now returned to its pre-stimulus condition, ready to respond to future hormone signals. The signal, of a water-soluble hormone binding to a receptor on the plasma membrane, is amplified through the activation of many G proteins and the generation of even more cyclic AMP. This cyclic AMP activates many protein kinases, which affect many thousands of introcellular proteins, all shaping the target cell's response. The response of many target cells produces the homeostatic and regulatory effects controlled by the endocrine system.
The endocrine system consists of hormone-producing tissues located throughout the body. The circulating hormones control the rates of body processes and maintain homeostasis. Within an endocrine gland endocrine cells secrete hormones which diffuse into nearby capillaries. The cardiovascular system transports these hormones throughout the body, affecting target cells in various tissues. Target cells for a specific hormone have receptors that bind the unique three-dimensional shape of that hormone. Cells that lack a specific hormone receptor are unresponsive to that hormone, even if a high concentration of the hormone is present around the cells. Although cells express a variety of receptors, we'll focus on one particular class: receptors that bind water-soluble hormones and exert their effects through the intracellular second messenger cyclic AMP. These receptors are embedded in the cell's plasma membrane, because water-soluble hormones cannot enter the target cell directly. A hormone molecule, acting as the first messenger, binds to its receptor, causing the receptor to change shape. The receptor can now activate specific intracellular G proteins. The activation process begins with the release of a GDP molecule from the G protein in exchange for a GTP molecule. This causes the G protein to change shape and become active. The hormone-bound receptor activates many individual G proteins, which greatly amplifies the signal from a single hormone molecule. An activated G protein diffuses along the plasma membrane until it binds to, and activates, the enzyme adenylate cyclase. Once active, adenylate cyclase converts ATP to the second messenger cyclic AMP. These many molecules of cyclic AMP, from each activated cyclase enzyme, represent a further amplification of the initial hormone signal. The increased concentration of cyclic AMP activates enzymes known as protein kinases. These activated protein kinases phosphorylate a variety of proteins within the cell. This changes the activity of those proteins and generates the cell's hormone response. The cell's response is characterized by the specific proteins present in the cytoplasm, only some of which can be phosphorylated by protein kinase. The cellular response diminishes rapidly once the hormone is no longer bound to its receptor. G proteins hydrolyze their bound GTP to GDP, returning to their inactive state, and dissociate from adenylate cyclase. This ends cyclic AMP production. Existing cyclic AMP is degraded by the enzyme phosphodiesterase, which is already present in the cyctoplasm. As the cyclic AMP concentration returns to resting levels, protein kinase inactivates, preventing further protein phosphorylation. The target cell has now returned to its pre-stimulus condition, ready to respond to future hormone signals. The signal, of a water-soluble hormone binding to a receptor on the plasma membrane, is amplified through the activation of many G proteins and the generation of even more cyclic AMP. This cyclic AMP activates many protein kinases, which affect many thousands of introcellular proteins, all shaping the target cell's response. The response of many target cells produces the homeostatic and regulatory effects controlled by the endocrine system.