The Role of ER-Alpha and the Ovaries in the Enduring Altered Behavioral Response to Pubertal Immune Stress

• Main Author: Rappleyea, Bethany
• Format: Others
• Published: ScholarWorks@UMass Amherst 2014
• Subjects: Puberty; Estradiol; ER-Alpha; LPS; Ovaries; Female; Behavioral Neurobiology; Biology; Molecular and Cellular Neuroscience
• Online Access: https://scholarworks.umass.edu/theses/1197; https://scholarworks.umass.edu/cgi/viewcontent.cgi?article=2334&context=theses

Peripubertal immune stress alters adult responsiveness to estradiol (E2) and progesterone (P). When female mice are injected with the bacterial endotoxin lipopolysaccharide (LPS) at six weeks of age, or during pubertal development, they display a decrease in response to ovarian hormones. In contrast, females ovariectomized prior to peripubertal immune stress display typical levels of sexual behavior following sequential injections of E2 and P in adulthood. Additionally, intact females exposed to peripubertal immune stress display a decrease in estrogen receptor alpha (ER-α)-immunoreactive (ir) cells in the medial preoptic area (MPOA) and ventromedial nucleus of the hypothalamus (VMH) in adulthood. However, ER-α has not been studied in mice that have been ovariectomized prior to receiving LPS. The objective of the present study is two-fold: to replicate the finding that ovariectomy prior to pubertal development prevents the deleterious effects of LPS administration, and to examine the status of ER-α in areas of the brain important to sex behavior. We predicted that mice ovariectomized after LPS injection would display fewer ER-α-ir cells and a decreased responsiveness to ovarian hormones than saline controls and those mice ovariectomized prior to LPS injection. To test this, female mice were ovariectomized or sham-operated prior to LPS treatment. Then, at six weeks of age, all mice were injected with saline or LPS. Following that, sham-operated mice were ovariectomized and ovariectomized mice were sham-operated. Mice were primed weekly with E2 and P, and sex behavior testing occurred once a week for 5 weeks. After the final behavior test, all mice were euthanized, their brains removed, and stained for ER-α via immunocytochemistry. Results revealed a large variability in hormone responsiveness. However, animals that received peripubertal LPS, but still had their ovaries, had significantly lower sexual receptivity when compared to animals that were ovariectomized prior to the pubertal period and given LPS. Further, there were no differences between groups in ER-α-ir numbers. External environmental stressors, such as animal housing and vibrations and noise from nearby construction, may have caused some of the results found here, which are inconsistent with previous findings.