Modifications in the phosphoinositide signaling pathway by adrenal glucocorticoids in rat brain: Focus on phosphoinositide-specific phospholipase C and inositol 1,4,5-trisphosphate

The hypothalamic-pituitary-adrenal (HPA) axis has been shown to be involved in mood and behavior. The possibility that adrenal glucocorticoids regulat e components of the phosphatidylinositol (PI) signal transduction pathway w as investigated. Two different doses of corticosterone (CORT) pellets (50 o r 100 mg) were implanted in normal and bilaterally adrenalectomized (ADX) r ats, and CORT regulation of the expression of G(q) alpha protein, phospholi pase C (PLC) isozymes, inositol 1,4,5-trisphosphate receptor (IP3R) isoform s, and of PI-PLC activity, [H-3]IP3 binding to IP(3)Rs, and IP3 levels were measured in various brain areas after 1 or 14 days. Fourteen days of CORT pellet implantation into normal rats dose dependently decreased PI-PLC acti vity and selectively the mRNA and protein expression of PLC beta 1 isozyme in cortex and hippocampus. Bilateral ADX caused the opposite changes in the se measures, and simultaneous CORT pellet implantation into ADX rats revers ed these effects. Furthermore, 14 days of CORT treatment of normal rats inc reased [H-3]IP3 binding to IP(3)Rs and decreased IP3 levels in cortex, hipp ocampus, and cerebellum, without any changes in expression of IP3R-I, IP3R- II, or IP3R-III isoform. On the other hand, ADX decreased [H-3]IP3 binding and increased levels of IP3, and simultaneous CORT treatment of ADX rats pr evented these changes. ADX or CORT treatment had no significant effects on the expression of G(q/11) alpha protein. These results suggest that manipul ation of the HPA axis alters various components of the PI signaling pathway in rat brain, which may have physiological relevance to the HPA axis-media ted changes in mood and behavior.