Hormones are chemical messengers that regulate various bodily functions. They work by binding to specific receptors, triggering a cascade of events inside cells. This process, called signal transduction, involves second messengers and protein kinases that amplify the hormone's effects.
Hormone action doesn't stop at the cell surface. Many hormones influence gene expression by binding to . These receptors interact with DNA sequences called , controlling which genes are turned on or off. This intricate system is kept in check through mechanisms.
Hormone Receptors
Types of Receptors
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Receptor proteins are specialized molecules that bind to specific hormones
Two main categories of hormone receptors include membrane receptors and nuclear receptors
Membrane receptors are located on the cell surface and bind to hydrophilic hormones that cannot pass through the lipid bilayer (peptide hormones, catecholamines)
Nuclear receptors are located inside the cell and bind to lipophilic hormones that can diffuse across the cell membrane (steroid hormones, )
G Protein-Coupled Receptors (GPCRs)
G protein-coupled receptors (GPCRs) are a large family of membrane receptors that transduce signals via guanine nucleotide-binding proteins (G proteins)
GPCRs consist of seven transmembrane domains, an extracellular ligand-binding domain, and an intracellular domain that interacts with G proteins
When a hormone binds to a GPCR, it induces a conformational change that activates the associated G protein, which then initiates a signaling cascade within the cell
Examples of hormones that use GPCRs include , , and
Signal Transduction
Second Messengers
Second messengers are small, diffusible molecules that relay signals from membrane receptors to intracellular targets
Common second messengers include (cAMP), (Ca2+), and inositol trisphosphate (IP3)
Second messengers amplify the original hormone signal by activating multiple downstream effector molecules
For example, when epinephrine binds to its GPCR, it activates adenylyl cyclase, which converts ATP to cAMP, a second messenger that activates protein kinase A
Protein Kinases and Signal Amplification
Protein kinases are enzymes that phosphorylate target proteins, altering their activity or function
Many hormone signaling pathways involve a cascade of protein kinases, where each kinase activates the next, leading to
cAMP-dependent protein kinase (protein kinase A) is a key enzyme in many hormone signaling pathways
When cAMP binds to protein kinase A, it causes the enzyme to dissociate into its regulatory and catalytic subunits
The catalytic subunits then phosphorylate various target proteins, such as enzymes, transcription factors, and ion channels
This amplification allows a small number of hormone molecules to elicit a large cellular response
Gene Regulation
Hormone Response Elements
Hormone response elements (HREs) are specific DNA sequences located in the promoter regions of hormone-responsive genes
Nuclear receptors, when bound to their respective hormones, can directly bind to HREs and regulate gene transcription
For example, the , when bound to estrogen, forms dimers that bind to estrogen response elements (EREs) in the promoters of estrogen-responsive genes, activating their transcription
HREs allow hormones to directly control the expression of specific genes, leading to changes in cellular function and physiology
Negative Feedback
Negative feedback is a regulatory mechanism that maintains homeostasis by reducing the output of a system when the input increases
In the context of hormone signaling, negative feedback occurs when the effects of a hormone inhibit its own secretion or the secretion of its releasing hormone
For instance, high levels of thyroid hormones (T3 and T4) inhibit the release of (TSH) from the anterior pituitary gland and (TRH) from the hypothalamus
Negative feedback helps prevent excessive hormone secretion and maintains stable hormone levels within a physiological range