Repeated Administration of Dexamethasone Increases Phosphoinositide‐Specific Phospholipase C Activity and mRNA and Protein Expression of the Phospholipase C β1 Isozyme in Rat Brain

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Abstract
: Altered hypothalamic‐pituitary‐adrenal (HPA) function has been shown to be associated with changes in mood and behavior. The enzyme phosphoinositide‐specific phospholipase C (PI‐PLC), an important component of the PI signal transduction system, plays a major role in mediating various physiological functions. In the present study, we investigated the effects of a single dose and of repeated administration (0.5 or 1.0 mg/kg for 10 days) of dexamethasone (DEX), a synthetic glucocorticoid, on PI‐PLC activity and on expression of PLC isozymes (β1, δ1, and γ1) 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 β1 isozyme in both membrane and cytosol fractions of cortex and hippocampus ; however, the repeated administration of a smaller dose of DEX (0.5 mg/kg) caused these changes only in hippocampus but not in cortex. The increase in PLC β1 protein was 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 significant effects on PI‐PLC activity or on the protein expression of PLC isozymes. These results suggest that DEX up‐regulates PI‐PLC in rat brain, which presumably is due to a selective increase in expression of the PLC β1 isozyme, and that these changes in PI‐PLC may be related to HPA axis‐mediated changes in mood and behavior.