21.5
Secondary Messengers in Hormone Action
Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling p…
Water-soluble hormones cannot move across the plasma membrane, so they use protein receptors that span the membrane to trigger intracellular signaling pathways.
These pathways activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that link to regulatory G proteins. G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C.
Adenylyl cyclase converts ATP to cAMP, which can activate protein kinases. Kinases are enzymes that add phosphate groups to other proteins, initiating a phosphorylation cascade.
Epinephrine, glucagon, parathyroid hormone, and luteinizing hormone act through cAMP.
Phospholipase C breaks down the membrane phospholipid PIP2 into IP3 and DAG.
IP3 then moves to the endoplasmic membrane and binds to an IP3-gated calcium channel, causing a release of calcium ions into the cytoplasm. The change in calcium concentration can induce physiological effects such as muscle contraction.
Oxytocin and hypothalamic regulatory hormones amplify signals through PIP2 and calcium ions.
View the full transcript and gain access to JoVE Core videos
Q1: Why do water-soluble hormones need second messengers to affect cells?
Water-soluble hormones cannot cross the plasma membrane directly, so they bind to transmembrane protein receptors on the cell surface. These receptors trigger intracellular signaling pathways that activate second messengers like cAMP or calcium ions inside the cell. Second messengers amplify and relay the hormone signal to produce physiological responses.
Q2: How do G protein-coupled receptors activate the cAMP signaling pathway?
G protein-coupled receptors span the plasma membrane and connect to regulatory G proteins. When a hormone binds, the G protein activates adenylyl cyclase, an enzyme that converts ATP to cAMP. cAMP then activates protein kinases, which add phosphate groups to other proteins, initiating a phosphorylation cascade that produces cellular effects.
Q3: What role does phospholipase C play in hormone signaling?
Phospholipase C breaks down the membrane phospholipid PIP2 into two second messengers: IP3 and DAG. IP3 travels to the endoplasmic reticulum and binds to IP3-gated calcium channels, releasing calcium ions into the cytoplasm. This increase in calcium concentration triggers physiological responses such as muscle contraction.
Q4: Which hormones use cAMP as their primary second messenger?
Epinephrine, glucagon, parathyroid hormone, and luteinizing hormone all act through the cAMP signaling pathway. For example, epinephrine activates the β-adrenergic receptor to initiate the fight-or-flight response. These hormones rely on cAMP to amplify their signals and produce rapid cellular responses.
Q5: What is a phosphorylation cascade and why is it important in hormone signaling?
A phosphorylation cascade occurs when protein kinases add phosphate groups to other proteins, which then activate additional kinases in a chain reaction. This cascade amplifies the initial hormone signal, allowing a single hormone molecule to produce a large cellular response. Each step in the cascade increases the signal strength exponentially.
Q6: How do oxytocin and hypothalamic regulatory hormones differ from epinephrine in their signaling mechanism?
Oxytocin and hypothalamic regulatory hormones amplify signals through PIP2 breakdown and calcium ion release, using the phospholipase C pathway. In contrast, epinephrine uses the cAMP pathway through adenylyl cyclase activation. Both pathways are second messenger systems, but they activate different intracellular enzymes and produce distinct physiological outcomes.
Q7: How do protein kinases translate hormone signals into cellular responses?
Protein kinases are enzymes activated by second messengers like cAMP or calcium ions. They add phosphate groups to target proteins, altering their structure and function. This phosphorylation initiates a cascade of molecular events that ultimately produces physiological effects such as changes in metabolism, muscle contraction, or gene expression.