Mechanisms of Hormone Action

Fundamentals of Hormonal Signal Transduction

Hormonal signal transmission in a target cell always begins when a hormone (the primary messenger) finds its specific receptor. As soon as they bind, an obligatory spatial structure (conformation) change occurs in the receptor. The modified molecule then actively interacts with other intracellular macromolecules. This process of molecular coupling is called signal transduction, generating a robust signal that regulates the cellular response.

The culmination of this cascade is always a change in the rate of metabolic reactions. The cell achieves this via two overarching pathways:

• Altering the activity of pre-existing enzymes (e.g., through chemical modification such as phosphorylation).
• Altering the abundance of enzymes (by enhancing or suppressing their synthesis).

Which pathway the signal takes depends directly on the receptor's localization: on the membrane or inside the cell.

Signal Transmission via Membrane Receptors

Receptors embedded in the plasma membrane receive signals from hormones that cannot cross the cell membrane. This group of ligands includes peptide hormones, epinephrine, and local mediators (cytokines, eicosanoids). Their mechanisms of action are realized through two main pathways.

The G-Protein and Second Messenger Pathway

1. Hormone binding to the receptor on the membrane surface.
2. Activation of a specific G-protein.
3. Activation of effector enzymes: adenylyl cyclase, guanylyl cyclase, or phospholipase C.
4. Generation of secondary messengers. These include cAMP, cGMP, inositol trisphosphate (IP₃), diacylglycerol (DAG), and Ca²⁺ ions.
5. Activation of protein kinases by secondary messengers.
6. Phosphorylation of intracellular proteins.
7. Result: Alteration of functional protein activity, leading to changes in metabolic rate.

The Autophosphorylation Pathway This pathway is characteristic of receptors with intrinsic tyrosine kinase activity.

• The hormone binds to the receptor.
• Autophosphorylation of the receptor itself occurs.
• A powerful phosphorylation cascade of various intracellular proteins is triggered.
• Enzymes and transcription factors are activated.
• Result: Alteration in the quantity of synthesized proteins (and their functional activity), changing the metabolic rate.

Action via Intracellular Receptors

If a hormone can cross the cell membrane, its receptors are located intracellularly—in the cytosol or cell nucleus. Typical ligands for this mechanism include steroid hormones and thyroxine. Their action unfolds in sequential steps:

1. Free diffusion of the hormone into the cell.
2. Binding to the receptor in the intracellular space.
3. Formation of a stable, active hormone-receptor complex.
4. Transport of the resulting complex directly into the cell nucleus.
5. Interaction of the complex with DNA (specific binding to regulatory regions: enhancers or silencers).
6. Induction (activation) or repression (suppression) of protein synthesis at the transcription stage.
7. Alteration in the actual quantity of proteins and enzymes in the cell.
8. Result: Sustained change in metabolic rate.