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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

Summer 2014

First Advisor

Sandra L. Petersen

Second Advisor

Robert Thomas Zoeller

Third Advisor

Kathleen F. Arcaro

Fourth Advisor

Sallie Smith-Schneider

Subject Categories

Molecular Biology

Abstract

Estradiol (E2) is critical in the reproductive mechanisms of mammals. In female rodents E2 acts through the neurons of the anteroventral periventricular nucleus (AVPV) to exert neuroendocrine control over ovulation, via synaptic activation of the gonadotropin releasing hormone (GnRH) neurons. The neurocircuitry of the AVPV is complex, receiving input from the suprachiasmatic nucleus and ventral premammillary nucleus and the as well as projecting to organum vasculosum of lamina terminalis and the arcuate. This suggests a broader role for the AVPV as a center of multisignal-integration in regards to ovulation. I used full genome expression microarrays to assess the E2-induced transcriptome in the female mouse AVPV and further investigated several targets using mouse neuronal cells. I discovered that within the AVPV, E2 regulates several genes important for energy balance. Additionally, I found that E2 regulates transcription factor v-ets avian erythroblastosis virus E26 oncogene homolog 2 (Ets2), which in turn regulates estrogen receptor α and is necessary in the E2-dependent regulation of kisspeptin. Together these findings support a broader role for AVPV function and identify a novel mechanism by which E2 mediates transcription.

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