Gene expression profile analysis of the rat basal forebrain in response to hormonal status
Author Block: *J. W. Lunden1, P. E. Micevych2, S. de Lacalle3;
1Cal State Los Angeles, Los Angeles, CA, 2Neurobiology, UCLA, Los Angeles, CA, 3Biomedical
Sciences, Charles R. Drew U., Los Angeles, CA.
Gene expression is a highly complex and tightly regulated process that allows a cell to respond dynamically both to environmental stimuli and to its own changing needs. This mechanism acts as an on/off switch to control which genes are expressed in a cell, and as a volume control that increases or decreases the level of expression of particular genes as necessary. Estrogen exerts powerful influences on the basal forebrain region, suggesting an anatomical location for some of its broad behavioral effects. We speculate that altered levels of circulating estrogen may result in long lasting, deleterious changes in gene expression, and used the Affymetrix Rat Genome 230 2.0 array to test our hypothesis, determining global differences in basal forebrain gene expression across the estrous cycle and in ovariectomized rats treated with estrogen or oil. Data was analyzed using Genesifter software, having computed RMA expression values, applying a 1.5 fold cutoff and p<0.05 (t-test and ANOVA). With this stringent filter, in gonadectomized animals we identified 138 transcripts differentially expressed between the estrogen and oil groups (n=4 each), representing <.5% of all probe sets examined. Of those, 60 genes responded to estrogen deprivation with up regulation of their expression, and 78 responded with down regulation. Among those significantly changed by the lack of estrogen, 11 genes were classified in the response to stimulus category (5 down- and 6 up-regulated), 5 were involved in cell death (up-regulated), 15 belonged to plasma membrane (7 up- and 8 down-regulated), and 25 related to binding (13 down- and 12up-regulated). In the intact cycling animals (n=4 each group), 142 genes (also less than .5% of all probe sets examined) were differentially expressed across 3 time points of the estrous cycle, determined by vaginal cytology: 10 a.m. of proestrus, 6 p.m. of proestrus, and 10 a.m. of estrus. Using the Gene Ontology classification, we examined changes in the expression of subsets of genes related to biological processes (response to stress and behavior), cellular components (plasma membrane) and molecular function (binding), and found that levels of expression were consistently higher at 10 a.m. of estrus followed by 10 a.m. of proestrus, with the lowest at 6 p.m. of proestrus, suggesting an inverse relationship between those particular genes and circulating levels of estrogen.
Author Disclosure Block: J.W. Lunden, None; P.E. Micevych, None; S. de Lacalle, None.
Theme and Topic (Complete): D.1.b. Cellular signaling ; E.4.e. Regulatory factors (hormones,