Cells not only interact with their immediate microenvironment, but may also detect and respond to signals originating much further away. Signaling pathways may be classified according to the source of a signaling molecule or ligand.

Depending on the ligand’s origin (from the same cell, from the neighbour cell or from far distance), recptor-ligand interaction and signaling pathway activation is classified into four different types: autocrine, endocrine, paracrine and juxtacrine. Activation of either of these pathways ultimately results in gene expression.

Endocrine signaling

Endocrine signaling is an example of long distance communication between hormone producing cells, tissues and glands and cells that express hormone receptor molecules. The hormones themselves are small molecules or glycoproteins that are usually secreted into the blood stream before being distributed throughout the body. Endocrine signals often originate from within the brain, however other glands and organs, including the thyroid gland, stomach, pancreas, liver, kidneys and reproductive organs, also produces hormones. One endocrine signal that must travel a great distance is that of follicle-stimulating hormone (FSH), which is sent from the anterior pituitary gland to the testes or ovaries where it stimulates the maturation of germ cells.

Paracrine signaling

Paracrine signaling occurs between cells in close proximity to each other. Here, a soluble signaling molecule secreted by one cell diffuses to another cell in the local neighborhood. For instance, neurotransmitters secreted by neurons diffuse a few nanometers before binding to receptors on target neurons or muscle cells. Another example is the release of chemokines by neutrophils, which attract other cells through a process known as chemotaxis.

Juxtacrine signaling

Juxtacrine signaling occurs between neighboring cells that are in physical contact with each other. In this case, the signaling molecule is not free, but is instead bound to the membrane of the cell. It may then interact with a receptor on the membrane of an adjacent cell. An example of juxtacrine signaling is the interaction between the notch receptor, and its ligand, ‘delta’. Cell-cell junctions that contain cadherin complexes also work in a similar manner.

Autocrine signaling

In autocrine signaling, the signaling molecule originates from the target cell itself. This occurs when cells express receptors to a ligand they secrete. For example, blood platelets secrete eicosanoids, which influence their own activity. Autocrine signaling has also been observed during embryo development.