Lipocortins are phospholipase inhibitory proteins, which we discovered and characterized as second messengers of glucocorticoids, hormones from the adrenal cortex. The induction of the synthesis of these proteins by glucocorticoids occurs even in physiological doses and purified lipocortins can mimic some actions of glucocorticoids such as anti-inflammatory actions, immunosuppression, anti-edema action and arrest of cellular growth. These actions are attributable to the regulation of hormone-or neurotransmitter-induced phospholipid metabolisms (phosphatidylcholine and polyphosphoinositide turnovers) by lipocortins. Since lipocortins phosphorylated by tyrosine kinases and serine/threonine kinases are inactive to inhibit phospholipases, phosphorylation-dephosphorylation appears to play an important role in such regulation. Tyrosine kinases are closely associated with growth factor receptors such as EGF and insulin receptors, whereas serine/threonine kinases including protein kinase C are involved in bradykinin, fMetLeuPhe and other receptors. All these observations implicate that noxious stimuli such as stresses can cause immunosuppression by inducing the synthesis of lipocortins via hypercorticoidemia and that various receptor functions can be modulated by phosphorylation-dephosphorylation of lipocortins. Thus, glucocorticoids can exert their many actions in various tissues and organs, mediating through lipocortins.
