Paracrine Signaling

Cells can communicate, with one another, in several distinct ways. One of the most important ways is paracrine signaling, the topic of this lesson. There are examples of paracrine signaling all over the human body, and indeed, examining certain molecular pathways in our bodies is one of the best ways of understanding the mechanism of this form of cell signaling. Paracrine signaling helps to alter features of our blood vessels, as well as other organs. Let's look at some of these examples.

Definition of paracrine signaling/secretion

Paracrine signaling, also known as paracrine secretion, is a form of cellular signaling in which cells communicate over relatively short distances by the release (secretion) of small signaling molecules onto nearby cells.

Figure 1: A visual representation of paracrine communication.

Key Features of Paracrine Signaling

• It is a form of cell signaling

  • The other forms, besides paracrine signaling, are endocrine signaling, autocrine signaling, and signals via direct contact.

• It happens via the release of small molecules

  • An example of one is nitric oxide (NO); we'll talk about it more below.

• It occurs between cells (individuals or groups) that are close in proximity to one another

  • There is a short distance between the cells that secrete or release the signals and the target cells that are altered by these signals.

What are paracrine factors?

These small signaling molecules we will discuss throughout this lesson also have another name. They are called paracrine factors, and they are distinguished by their ability to travel short distances and then enter target cells. Often times paracrine factors enter target cells by diffusion, but there are other methods of entry as well, some of which include receptor binding.

Example of paracrine signaling

As promised, here is an in-depth example of paracrine signaling, using the signaling molecule nitric oxide (chemical formula = NO).

Our blood vessels are hollow tubes, and the walls of these tubes are actually comprised of several layers.

• The outermost layer is known as the adventitia, which is often fibrous and made of different kinds of collagen.

• The middle layer is muscular, known as the media, and is comprised of smooth muscle.

• Finally, the innermost layer, which is the last layer before the hollow center, is called the intima, and the thin film of cells that lies atop is called the endothelium.

Figure 2: Layers of blood vessels.

How does all this relate to paracrine signaling? Well, one of the functions of the endothelium is to produce none other than Nitric Oxide! And nitric oxide produced by the cells of the endothelium then acts as a small signaling molecule diffusing into nearby smooth muscle cells. Nitric oxide causes smooth muscle relaxation in these cells, which leads to blood vessel dilation.

Nitric oxide has only a very short half-life (lasting about 5 seconds), so only a finite amount of gas can act on a finite number of nearby cells before it all dissipates. This is part of the reason that nitric oxide can act as a paracrine signaling molecule, because it can produce its effects only on nearby target cells, and not on cells that are quite far away. Also, because the mechanism of dispersal of the signaling molecule is simple diffusion, the closer a target cell is, the more likely it is to receive the signal.

Now, we've learned some biological principles and also the physiology behind nitric oxide as a mediator for vasodilation (blood vessel dilation). With all this in mind, let's remind ourselves of how nitric oxide fulfills the criteria for being an agent of paracrine signaling.

1. Nitric oxide is the signal, it is a small molecule that leads to effects and/or alterations in target cells.

2. Nitric oxide only travels short distances, to nearby cells.

3. Nitric oxide is taken up in these cells by diffusion, not through the blood.

The effect of paracrine signaling

To look at the effect of paracrine signaling, we'll use another example. This time, it occurs in our limbs, and it also occurs during our fetal development. We are talking about the Hedgehog transcription factors. What are transcription factors?

What is a hedgehog besides a cute, prickly animal? In developmental cellular biology, the Hedgehog family (including, sometimes, the sonic hedgehog protein) is a family of proteins that help to order body parts in their right place. It gives organs and organisms their orientations and orderly patterns, and this largely happens in developing fetuses.

In humans, hedgehog proteins are involved in planning everything from our brain positions and patterns to our guts to our limbs to our lungs.

Hedgehog proteins can be secreted by certain cells and bind to cell receptors on nearby cells. This binding causes signal transduction, where certain changes in the target cell occur in response to signal binding. These changes ultimately lead to the proper limbs and organs developing in the right way, in response to their hedgehog signals.

And what form of signal transduction is this specifically? Paracrine signaling. These hedgehog proteins must only act over short distances of course so that they only instruct the cells nearest to them. If they could travel far away from their site of origin, you might have fingers developing on the wrist and elbow, not just the hand.

The difference between autocrine and paracrine

Hopefully, by now, we have a great, in-depth understanding of paracrine signaling. So, let's compare it directly to another form of cell communication - autocrine signaling.

First, we must briefly note what autocrine signaling is. This is when a cell releases a signal for itself and then undergoes some changes or alterations due to this signal.