Water – soluble hormone binds to a receptor protein on the surface of a target cell. This interaction triggers a signal transduction pathway that leads to a change in a cytoplasmic function or a change in gene transcription in the nucleus. A lipid – soluble hormone penetrates the target cell's plasma membrane and binds to an intracellular receptor, either in the cytoplasm or in the nucleus. The signal – receptor complex acts as a transcription factor, typically activating gene expression. Early evidence for the role of cell – surface receptors in triggering signal transduction pathways came from studies on how the hormone epinephrine stimulates breakdown of glycogen to glucose.

Another demonstration of the role of cell – surface receptors involves changes in a frog's skin color, an adaptation that helps camouflage the frog in changing light. Skin cells called melanocytes contain the dark brown pigment melanin in cytoplasmic organelles called melanosomes. The frog's skin appears light when melanosomes cluster tightly around the cell nuclei and darker when melanosomes spread throughout the cytoplasm.

A peptide hormone called melanocyte – stimulating hormone controls the arrangement of melanosomes and thus the frog's skin color. Adding melanocyte – stimulating hormone to the interstitial fluid surrounding the pigment – containing cells causes the melanosomes to disperse. However, direct microinjection of melanocyte – stimulating hormone into individual melanocytes does not induce melanosome dispersion – evidence that interaction between the hormone and a surface receptor is required for hormone action. Epinephrine, the primary fight – or – flight–hormone, produces different responses in different target cells. Responses of target cells may differ if they have different receptors for a hormone. Target cells with the same receptor exhibit different responses if they have different signal transduction pathways and/or effector proteins.