Repeated administration of dexamethasone increases phosphoinositide-specific phospholipase C activity and mRNA and protein expression of the phospholipase C beta(1) isozyme in rat brain

Altered hypothalamic-pituitary-adrenal (HPA) function has been shown to be associated with changes in mood and behavior. The enzyme phosphoinositide-s pecific phospholipase C (PI-PLC), an important component of the PI signal t ransduction system, plays a major role in mediating various physiological f unctions. In the present study, we investigated the effects of a single dos e and of repeated administration (0.5 or 1.0 mg/kg for 10 days) of dexameth asone (DEX), a synthetic glucocorticoid, on PI-PLC activity and on expressi on of PLC isozymes (beta(1), delta(1), and gamma(1)) in rat brain. Repeated administration of DEX (1.0 mg/kg) caused a significant increase in PI-PLC activity and in protein expression of the PLC beta(1) isozyme in both membr ane and cytosol fractions of cortex and hippocampus; however, the repeated administration of a smaller dose of DEX (0.5 mg/kg) caused these changes on ly in hippocampus but not in cortex. The increase in PLC beta(1) protein wa s associated with an increase in its mRNA level, as measured by competitive RT-PCR. A single administration of DEX (0.5 or 1.0 mg/kg) to rats had no s ignificant effects on PI-PLC activity or on the protein expression of PLC i sozymes. These results suggest that DEX up-regulates PI-PLC in rat brain, w hich presumably is due to a selective increase in expression of the PLC bet a(1) isozyme, and that these changes in PI-PLC may be related to HPA axis-m ediated changes in mood and behavior.