Rapid corticosteroid-dependent regulation of mineralocorticoid receptor protein expression in XXXX brain.

@entity230 @entity1369 @entity2819 @entity7834 @entity35
Corticosteroid hormones regulate many aspects of neural function via mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Although GR expression is negatively regulated by endogenous corticosteroids, the autologous regulation of MR expression has been less well studied, partly due to limitations of receptor binding assays that cannot measure the ligand-activated form of MR. Using MR-reactive antibodies and Western blot, we examined relative MR protein expression in @entity35 brain and its potential autoregulation by corticosteroids. We found that MR protein expression is autoregulated in a negative fashion by adrenal @entity230 . Compared with GR, we see a more rapid regulation of MR, such that there is a substantial increase in MR protein within 12 h after adrenalectomy, whereas GR levels show very little increase until more than 24 h after adrenalectomy. Also, in contrast to GR, which has been found to be regulated by both MR and GR, adrenalectomy-induced increase in MR was prevented by treatment with the MR selective agonist, @entity1369 , but not the GR selective agonist, @entity7834 . Interestingly, acute treatment of adrenalectomized @entity35 with @entity2819 produced a significant decrease in whole-cell MR protein within 45 min, suggesting ligand-induced rapid degradation of MR. Chronic high levels of @entity2819 also produced a significant decrease in MR protein levels below adrenal-intact @entity35 levels. These results have important implications for previous studies that estimated the proportion of MR that are occupied in vivo by various circulating levels of @entity2819 . Those studies compared available MR binding levels in adrenal-intact @entity35 with 24-h adrenalectomized @entity35 , with the assumption that there were no differences between the various conditions in total receptor expression. Those studies concluded that MR is nearly fully occupied by even the lowest circulating @entity2819 levels. Given the 2- to 3-fold increase in MR protein that we have observed within 24 h after adrenalectomy, it is likely that those studies significantly overestimated the proportion of MR that were occupied by low basal @entity2819 levels. These results support the prospect that MR as well as GR can participate in the transduction of phasic corticosteroid signals.
