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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.
The nearby target cells then react to this signal in some way, producing an effect.
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).
While you may be more familiar with it from general chemistry, nitric oxide is also a really important molecule in our bodies (in biology and physiology).
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.
Typically this lowers blood pressure, although it can also lead to red cheeks when you blush, penile erection and clitoral tumescence, and even dilation of your bronchi, depending on when and where the nitric oxide release occurs.
Perhaps you've heard of Viagra? It is one of the most recognizable, popular, and highly prescribed drugs the world over. Viagra is given to treat erectile dysfunction, and this medication's method of action is related to our example of paracrine signaling.
How do you ask? Well, Viagra works by increasing nitric oxide production in endothelial cells! All this increased nitric oxide can then act as a paracrine signal, diffusing to nearby smooth muscle cells in the genitals. Nitric oxide causes the smooth muscle cells to relax, leading to increased blood flow within the genitals, which leads to engorgement and corrects erectile dysfunction.
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.
Nitric oxide is the signal, it is a small molecule that leads to effects and/or alterations in target cells.
Nitric oxide only travels short distances, to nearby cells.
Nitric oxide is taken up in these cells by diffusion, not through the blood.
Seems like nitric oxide checks out! To hammer these principles home, let's look at another example.
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?
Transcription factors - these are proteins that influence, or even control, the rate and timing of the transcription of a certain gene.
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.
Hedgehog proteins were best studied in Drosophila fruit flies, and errors in them lead to misshapen fruit flies with eyes where their legs should be, legs where their eyes should be, and so on.
In humans, hedgehog proteins are involved in planning everything from our brain positions and patterns to our guts to our limbs to our lungs.
This family of proteins helps our organs to be in the right place.
In fact, some mutations in sonic hedgehog protein, in particular, can cause holoprosencephaly (when the brain doesn't divide into two hemispheres) which can even lead to cyclopia - having just one eye in the middle of the forehead!
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.
For example, the cells that will form the base of the finger might form in response to signal transduction via hedgehog proteins released from cells that will form the palm.
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.
The auto- in autocrine means "for self", so this is cell signaling for and by "self", where the self is a particular cell.
| Autocrine signaling | Paracrine signaling | |
| Acts on | The same cell it is released by | Nearby cells via diffusion or transduction |
| Typical signaling molecules | Growth factors and cytokines | Transcription factors and neurotransmitters |
| Typical cell releasing signal | WBCs | Neurons |
| When can it go wrong | Cancer-inducing cytokines, causing the growth of tumors | Cancer-inducing sonic-hedgehog proteins |
Features of paracrine signaling
Now that we know so much about paracrine signaling, let us recap the factors that give paracrine signaling its distinguishing features as a form of cell signaling.
Paracrine signals only travel short distances.
Paracrine signals only affect (relatively) nearby cells.
Paracrine signals are not transmitted through the blood.
Instead, they diffuse directly or get taken up by receptors to cause signal transduction.
Paracrine signals are very important in localized adjustments in blood vessel dilation: things like blood pressure, genital engorgement, and face flushing.
Paracrine signals are used to help pattern the order and orientation of many species' bodies via transcription factors.
Paracrine Signaling - Key takeaways
- Paracrine signaling is one of the four forms of cell signaling, including autocrine, endocrine, and direct-contact signaling.
- Paracrine signaling occurs when small signaling molecules are transmitted to target cells only short distances away, which then undergo some alteration or effect.
- Nitric oxide mediation of blood vessel dilation utilizes paracrine signaling to control nearby smooth muscle cells' relaxation.
- Hedgehog proteins utilize paracrine signaling to help determine the orientation and patterns of body organs in animals from fruit flies to human beings.
- Paracrine signaling occurs on nearby target cells, while autocrine signaling occurs on the same cell that released the signal.
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Frequently Asked Questions about Paracrine Signaling
What is paracrine signaling?
Paracrine signaling is a form of cell communication in which small molecules (signals) are released onto very nearby target cells, without going through the bloodstream.
What happens during the process of paracrine signaling?
Small molecules diffuse or get transduced onto/in to target cells, and cause an effect. This process occurs only over short distances.
What is paracrine?
Paracrine describes a form of cell signaling that occurs only between cells near to each other, and does not occur through the blood.
What is the difference between autocrine and paracrine?
Autocrine signaling is when a cell releases a signal for ITSELF, while paracrine signaling is when a cell releases a signal for other nearby cells.
What are paracrine factors?
Paracrine factors are the small molecules (such as NO) that can diffuse or be transduced to nearby cells to cause an effect.
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