HOW HORMONES WORK IN THE BODY

Mechanism of Action of Peptide Hormones

Peptide hormones are water-soluble and cannot diffuse through the lipid bilayer of the cell membrane. Their mechanism of action involves binding to specific receptors located on the surface of target cells, initiating a signaling cascade via second messengers.

1. Binding to Cell Surface Receptors: Peptide hormones bind to extracellular receptors on the plasma membrane of target cells because they are hydrophilic and cannot pass through the lipid bilayer.

2. Activation of G Proteins: The receptor-hormone complex activates intracellular G proteins associated with the receptor.

3. Second Messenger System:
   • The activated G protein stimulates an enzyme such as adenylyl cyclase or phospholipase C.
   • Adenylyl cyclase converts ATP into cyclic adenosine monophosphate (cAMP), which acts as a second messenger.
   • Alternatively, phospholipase C generates inositol triphosphate (IP3) and diacylglycerol (DAG), which also act as second messengers.

4. Signal Amplification: Second messengers activate protein kinases, which phosphorylate specific proteins within the cell, leading to changes in cellular activity.

5. Cellular Response: These changes may include alterations in enzyme activity, gene expression, or ion channel permeability, depending on the target cell and hormone involved.

Mechanism of Action of Amino Acid-Derived Hormones

Amino acid-derived hormones can act either through cell surface receptors (if they are water-soluble) or intracellular receptors (if they are lipid-soluble).

1. Water-Soluble Amino Acid-Derived Hormones (e.g., Epinephrine):
   • These hormones bind to extracellular receptors on the plasma membrane.
   • Similar to peptide hormones, they utilize second messenger systems like cAMP or IP3/DAG pathways.
   • For example, epinephrine binds to adrenergic receptors and activates a signaling cascade that results in physiological responses like increased heart rate or glycogen breakdown.

2. Lipid-Soluble Amino Acid-Derived Hormones (e.g., Thyroid Hormones):
   • Thyroid hormones can cross the plasma membrane due to their lipid solubility.
   • They bind to intracellular receptors located in the cytoplasm or nucleus.
   • The hormone-receptor complex interacts directly with DNA to regulate gene transcription and protein synthesis.

Mechanism of Action of Cholesterol-Derived Hormones

Cholesterol-derived hormones, also known as steroid hormones, are lipid-soluble and can diffuse across cell membranes to interact with intracellular receptors.

1. Diffusion Through Membrane: Steroid hormones like cortisol, testosterone, and estrogen easily pass through the lipid bilayer due to their hydrophobic nature.

2. Binding to Intracellular Receptors:
   • Inside the target cell, these hormones bind to specific cytoplasmic or nuclear receptors.
   • This forms a hormone-receptor complex.

3. Interaction with DNA:
   • The hormone-receptor complex translocates into the nucleus if it has not already bound there.
   • It binds directly to specific DNA sequences called hormone response elements (HREs).

4. Gene Transcription Regulation:
   • Binding at HREs triggers transcription of specific genes into mRNA.
   • The mRNA is translated into proteins that mediate physiological effects such as metabolism regulation or reproductive functions.

Mechanism of Action of Fatty Acid-Derived Hormones

Fatty acid-derived hormones include eicosanoids such as prostaglandins and leukotrienes; these are typically involved in paracrine signaling rather than endocrine signaling.

1. Synthesis at Target Site:
   • Fatty acid-derived hormones are synthesized locally from arachidonic acid by enzymes like cyclooxygenase (COX) for prostaglandins or lipoxygenase for leukotrienes.

2. Binding to Cell Surface Receptors:
   • These molecules usually act on nearby cells by binding to G-protein-coupled receptors (GPCRs) on their surfaces.

3. Second Messenger Activation:
   • Binding activates intracellular signaling cascades involving second messengers such as cAMP or calcium ions.

4. Local Cellular Effects:
   • Prostaglandins may mediate inflammation, pain sensation, or vasodilation.
   • Leukotrienes play roles in immune responses like bronchoconstriction during allergic reactions.