To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.