The phosphatidyl inositol (PI) second messenger pathway may mediate diverse effects of estrogen, including its potentiation of the effects of other hormones. Both estradiol (E2) and luteinizing hormone-releasing hormone (LHRH) induce a putative isoform of PI-specific phospholipase C-alpha (PLC-alpha). PLC-alpha catalyzes PI hydrolysis, which in turn can increase protein kinase C (PKC) activation, Ca2+ mobilization, and arachidonic acid metabolism. Estrogen activates the PI pathway, and components of the PI pathway can mimic or enhance some effects of estrogen. Furthermore, estrogen potentiates effects of several hormones (e.g., LHRH, prolactin, and insulin) which can also act through the PI system. PLC-alpha may therefore provide a common second messenger pathway mediating the potentiation by E2 of the effects of other hormones; in addition it may also mediate some or all of the many actions of E2, since components of the PI pathway can have secretory, trophic, toxic, and neuromodulatory effects.