Abstract

The use of estrogen is widespread among young women as a contraceptive and in older women for hormone replacement therapy. Although estrogen is known to have several beneficial effects on the brain, these effects are limited to non‐hypothalamic regions. Earlier studies have demonstrated inflammatory changes in the arcuate nucleus (AN) of the hypothalamus after E2 treatment. We hypothesized that chronic E2 exposure would increase the expression of cytokine and chemokine genes in the AN. To test this, young (Y) and middle aged (MA) female rats were sham implanted or implanted with slow release E2 pellets for 90 days. Ovariectomized Y and MA rats were treated the same way. At the end of treatment, animals were sacrificed and the AN was microdissected from brain sections. RNA extracted from the AN was subjected to a qPCR array. The array consisted of genes related to the inflammatory response like IL‐1β, TNF‐α, IL‐6, CCl2 and iNOS. In Y animals, E2 treatment significantly upregulated the following genes: IL‐6 by 3.73 fold, CCL2 by 4.76 fold, and iNOS by 9.42 fold compared to control (p<0.05). There was no change in the expression of these genes in MA animals after E2 treatment. These results indicate that chronic E2 exposure affects the expression of pro‐inflammatory genes in an age‐associated fashion. Supported by NIH AG027697.

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