All water-soluble hormones must bind to their specific membrane-bound or extracellular receptors on target cells. This results in the formation of the hormone-receptor complex. Hormones which interact with membrane-bound receptors normally do not enter the target cell, but generate second messengers (e.g., cyclic AMP, IP₃, Ca⁺⁺ etc) which in turn regulate cellular metabolism. E.g. peptide, polypeptide, protein hormones (e.g., insulin, glucagon, pituitary hormones, hypothalamic hormones, etc.)