DISTRIBUTION AND REGULATION OF CALMODULIN MESSENGER-RNAS IN RAT-BRAIN

Selective oligonucleotide probes were developed to determine the distribution and hormonal regulation of different calmodulin genes in rat brain and the relationship to calmodulin-dependent adenylate cyclase activity. (1) Probes directed against known CaMI, CaMII and CaMIII mRNA sequences selectively recognized molecular mRNA species of approximately 4.1 and 1.7 (CaMI mRNA), 1.4 (CaMII mRNA) and 2.0 and 1.0 kb (CaMIII mRNA) in rat brain. All three calmodulin genes appeared actively coexpressed at high levels in neuronal cell layers, as revealed by in situ hybridization and northern analysis. (2) Adrenalectomy selectively attenuated levels of CaMIII, but not CaMI or CaMII mRNA, in both cerebral cortex and hippocampus. (3) Adrenalectomy also decreased calmodulin dependent adenylate cyclase activity in hippocampal, but not cortical, cell membranes. (4) Corticosterone administration prevented adrenalectomy effects on hippocampal adenylate cyclase activity and calmodulin mRNA levels. However, steroid treatment also increased forskolin-stimulated enzyme activity in cerebral cortex, but not in hippocampus. These results suggest that hormonal factors regulate calmodulin gene expression in adult brain. Further evidence is required to establish the temporal interrelationships between steroid regulation of calmodulin and its target proteins.