MODULATION OF A NOVEL RNA IN BRAIN NEURONS BY GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS

A novel cDNA clone, CR16, was isolated from a rat hippocampal cDNA lib rary and characterized for responses to corticosteroids and regional e xpression. The 4-kb RNA was increased 3-fold by treatment of adrenalec tomized (ADX) rats with corticosterone (CORT). Overlapping cDNA totali ng 4,374 nt were used to define an open reading frame of 1,356 nt begi nning 191 nt from the 5'-end and encoding a 45-kD protein containing 3 2% proline. CR16 has no obvious homologies to GenBank or protein datab ases. CR16 RNA was detected by in situ hybridization in neuron-rich la yers of the hippocampal formation, layers II, III and VI of the cerebr al cortex, thalamus, ventromedial nucleus of the hypothalamus, bed nuc leus of the stria terminalis, lateral septal nucleus, nucleus accumben s, olfactory bulb, inferior colliculus, pens and inferior olive. The C R16 RNA has low prevalence in the hippocampus and cortex (<10 pg/mu g total RNA) and is elevated 3-fold in both structures in a dose-depende nt manner by CORT in ADX rats. Treatment of ADX rats with aldosterone (ALDO), CORT, or RU28362 increased CR16 RNA to similar levels in the h ippocampus while ALDO had minimal effects on the level of CR16 RNA rel ative to CORT or RU28362 in the cortex. Neither shaking stress (2 h) n or 2 h CORT significantly elevated CR 16 RNA in the hippocampus, sugge sting that its response to elevated CORT is not rapid. ADX lowered CR1 6 RNA levels by 50% relative to intact rats while low-level CORT repla cement (greater than or equal to 4 ng/ml serum CORT) significantly ele vated CR16 RNA 2-fold in ADX rats. These results are consistent with b oth the mineralocorticoid receptor (MR) and glucocorticoid receptor (G R) regulating the CR16 gene. This gene will be useful in dissecting th e role of MR and GR in CNS neurons.