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Estradiol Effects on Inflammation Related Gene Expression in the Nucleus Tractus Solitarius

Hormone replacement therapy is known to have significant effects on protein expression and function in brain regions important for blood pressure regulation. The nucleus of the solitary tract (NTS) is a key brainstem region involved blood pressure control and has been found to have sex differences in microglia activation during hypertension. The goal of the present study was to identify genes in the NTS sensitive to estradiol (E2) hormone replacement and may be involved in a hypertension induced brain inflammatory response. Affymetrix microarrays were used to compare mRNA levels in the NTS in ovariectomized female rats receiving either E2 (n=12) or saline (n=12) administered for 21 days via subcutaneous pellet implant. Using a combination of criteria, we identified a small set of genes on the array (6 of 431 significantly changed genes) with the largest significant responses to E2 and also known to be related to inflammation. Of these 6 genes, 5 were down‐regulated by E2 with negative fold changes including: ‐IL‐1 type 1 receptor, ‐47.2 fold change; LPS binding protein, ‐10.2 fold change; T‐cell receptor B‐chain, ‐6.4 fold change; tenascin‐C, ‐2.4 fold change and CD5 lymphocyte antigen, ‐1.97 fold change. The one significant fold increase was for heat‐shock protein (hsp) 70, + 3.1 fold change. These results may suggest that E2 hormone replacement therapy may affect brain blood pressure regulation by down‐regulating pro‐inflammatory genes and up‐regulating protective genes, such as hsp 70. NIH HL6226, HL098207.