The hormonal regulation of cellular functions depends primarily on the specificity of the hormone receptors. All cells can potentially come in contact with a hormone, but only those that have a specific receptor for that hormone will respond. Although different types of cells may have specific receptors for the same hormone, they will respond to that hormone in different ways. In other words, the receptor decodes the hormone message, but the specificity of the response is determined by the nature of the cell that responds, not by the hormone.

Hydrophilic hormones bind to receptors that span the plasma membrane. Different types of receptors transmit the hormonal signal to the interior of the cell in different ways.

Some receptors, when bound by hormone, have an enzymatic activity that phosphorylates proteins in the cytoplasm to activate or deactivate them. The insulin receptor functions in this way. Other receptors activate or inactivate a separate membrane-bound enzyme or ion channel. This activation is mediated by a protein in the plasma membrane. This protein, which binds guanosine triphosphate (GTP), acts as a transducer of the hormone signal. Receptors that act via GTP binding proteins are called G-protein- coupled receptors.

Let’s examine the most common action of G-protein-coupled receptors, the conversion of the hormone signal into a cascade of second messengers inside the cell.

When a hormone binds a G-protein- coupled receptor, a cascade of chemical events within the target cell is initiated that usually increases the concentration of second messengers.

A second messenger is a small molecule that relays the extracellular “first message” of the hormone into the cell. Proteins in the cell are then activated or deactivated by these second messengers. Because second messengers usually affect the function of proteins that already exist in the cell, responses are fast.

Many different second messenger chemicals have been identified. The most common are calcium ions and cyclic AMP, or cAMP.Second messengers both convey and amplify hormone signals inside cells. One hormone-binding event on the cell’s surface will activate many G-proteins. In turn, these G-proteins will send subunits to activate many adenylate cyclase proteins that convert ATP to cAMP. A hormone binding event is then greatly amplified by the production of many cAMP molecules.

The system is designed to automatically shut itself off. The activated adenylate cyclase is shut off when the G-protein subunit dephosphorylates the bound GTP to GDP.

The subunits reassemble, ready for activation by another hormone-receptor binding signal.

The hormone-receptor signal is terminated by endocytosis of the hormone-receptor complex. The receptors are then recycled back to the cell’s surface. Often the number of recycled receptors decreases following exposure to the hormone. This decrease in the number of cell-surface receptors is a form of down-regulation.

Now that we have looked in detail at one of the most common mechanisms of hydrophilic hormone action, lets turn our attention to the mechanism of action of lipophilic hormones. Lipophilic hormones pass through the cell’s plasma membrane. Once inside their target cells, they encounter specific intracellular receptors that share the following structures: an activating domain that binds to other transcription factors, a DNA-binding domain, and a hormone-binding domain.

When bound by hormone, the hormone-receptor complex changes shape, enabling the protein to bind to regulatory regions on specific genes. The bound hormone-receptor complex attracts transcriptional regulators, which then activate or suppress the transcription of the genes. In essence, the lipophilic hormone receptors are hormone-activated transcription factors. The products of some genes may change the function of the cell. Others may, in turn, activate other genes for a delayed secondary effect. Because it takes time for proteins to be synthesized, lipophilic hormones are best suited to controlling long-term processes such as the events of reproduction.

As long as the hormone concentration remains high, its receptors will probably have hormone bound to them. When the hormone concentration decreases, as hormone molecules disassociate from the receptors, it's not likely that another hormone molecule will be available to take their place. The activation then ends. Now that we’ve learned about how hormone action is initiated and terminated, let's look at some specific examples and explore ways of regulating hormone action to affect blood glucose levels.

Copyright 2006 The Regents of the University of California and Monterey Institute for Technology and Education