Hormones are chemical messengers secreted by endocrine glands that travel through the bloodstream to regulate the function of distant target cells. Their chemical structure dictates how they interact with the cell’s outer boundary. Peptide hormones, such as insulin and growth hormone, are a large and diverse group of these signaling molecules. The central question is how these molecules transmit instructions, given their inability to traverse the fatty barrier that encloses every cell.
Defining Peptide Hormones and the Cell Barrier
Peptide hormones are composed of chains of amino acids, ranging from small peptides to large proteins. Because they are assembled from amino acids, these hormones are water-soluble (hydrophilic), making them easy to transport through the blood plasma. However, their size and polarity make them incompatible with the cell membrane, which acts as a selective barrier.
The cell membrane is primarily constructed from a lipid bilayer, a double layer of phospholipid molecules. This bilayer has hydrophobic tails oriented inward and hydrophilic heads facing the outside and inside of the cell. This fatty, nonpolar core is an effective barrier against large, polar, and water-soluble molecules like peptide hormones. Consequently, passive diffusion, the simple movement across the membrane, is impossible for these substances.
The Mechanism of Action: Surface Receptors
Since the peptide hormone cannot enter the cell, the target cell must receive instructions from the outside. This is accomplished through specific transmembrane proteins known as surface receptors, which are embedded within the plasma membrane. These receptors possess an external binding site perfectly shaped to receive a specific hormone, functioning like a lock and key. The hormone binds to this extracellular domain of its matching receptor.
This binding event causes a change in the receptor’s three-dimensional shape, which transmits the signal across the membrane. The conformational change affects the receptor’s intracellular domain, located inside the cell’s cytoplasm. For example, when insulin binds to its receptor, the internal portion activates an intrinsic enzyme activity, specifically a tyrosine kinase. This activation step relays the signal without the hormone ever crossing the membrane barrier.
Signal Transduction and Cellular Response
The activation of the receptor’s internal domain initiates a chain reaction known as a signal transduction pathway. This process involves the generation or release of small, non-protein molecules within the cell called second messengers. Common examples include cyclic AMP (cAMP), calcium ions (Ca²⁺), and inositol triphosphate (IP₃).
The second messengers rapidly propagate the signal from the membrane deeper into the cell’s interior. For instance, activated receptors can stimulate an enzyme like adenylyl cyclase, which converts adenosine triphosphate (ATP) into numerous molecules of cyclic AMP. This amplification allows a single hormone molecule binding to the surface to trigger a large response inside the cell. The second messengers then activate various protein kinases, enzymes that add phosphate groups to other proteins. This phosphorylation cascade rapidly alters the activity of target enzymes or regulatory proteins, leading to the cell’s final response, such as activating a metabolic pathway or modulating gene transcription.
Contrast: Hormones That Do Cross the Membrane
The mechanism of peptide hormones contrasts with that of lipid-soluble hormones, such as steroid hormones like testosterone and cortisol. Steroid hormones are derived from cholesterol, giving them a nonpolar, hydrophobic structure. This structure allows them to diffuse directly across the fatty lipid bilayer of the cell membrane without needing a surface receptor.
Once inside the cell, these lipid-soluble hormones bind to receptors located in the cytoplasm or the nucleus. The hormone-receptor complex then travels to the nucleus, where it binds directly to specific DNA sequences. This binding acts as a transcription factor, changing the expression of specific genes. This results in a slower, but more sustained, cellular change compared to the rapid effects of peptide hormones.