Glucocorticoid Regulation of Preproenkephalin Messenger Ribonucleic Acid in the Rat Striatum*

Abstract

Glucocorticoids regulate the level of preproenkephalin mRNA expression in a number of cell systems. This study investigated the expression of preproenkephalin mRNA in the brain and its regulation by glucocorticoids in vivo. Two different methods for mRNA quantitation were employed. Total RNA isolated from dissected brain tissue was analyzed in an RNAse T2 protection assay. In addition, we have used in situ hybridization to brain sections to assess the expression of preproenkephalin mRNA. The results demonstrate that in the straitum the preproenkephalin mRNA is expressed at a high level and is regulated by glucocorticoids. There is a decrease in striatal preproenkephalin mRNA after adrenalectomy (ADX), and ADX animals replaced with corticosterone express higher levels of striatal preproenkephalin mRNA than ADX animals. By in situ hybridization we have determined that the corticosterone-induced increase in striatal preproenkephalin mRNA is evident after 16 h, but not after 2 h, of corticosterone replacement of ADX animals. Elevation of circulating corticosterone levels in intact rats by 2-3 h of restraint stress, a multiple daily stress regimen over 1-21 days, or corticosterone injection did not change the level of preproenkephalin mRNA in the striatum; however, a single 16-h restraint stress resulted in a decreased level of expression. In intact rats there was a diurnal variation in the level of striatal preproenkephalin mRNA expression; ADX resulted in a decrease in the mRNA level, but did not abolish the diurnal variation in expression. Thus, while there is clearly regulation of striatal preproenkephalin mRNA by glucocorticoids, our results provide evidence for regulation by nonglucocorticoid mechanisms as well.