The Identification of Transcriptional Signatures of Steroid Response in Human Neurons and Microrna Networks as a Contributor to Reproductive Steroid Pathology
Year: 2021
Type: dissertation
Abstract: Ovarian steroids change the brain in utero, during puberty, and in adulthood.At the neuronal level, ovarian steroids affect structure, gene networks, and physiological outputs, and at the neurocircuitry level they modulate working memory, reward, and emotion.In reproductive related affective disorders such as premenstrual dysphoric disorder (PMDD), alterations in mood and affect are linked to changes in ovarian steroid levels.However, the pathophysiology of these disorders is just beginning to be characterized.For PMDD, previous work demonstrated intrinsic differences in the ESC/E(Z) complex, a major epigenetic modifier.However, this work showed a discrepancy between transcripts and protein: while transcripts in this complex tend to be upregulated in PMDD, protein quantities were downregulated.The work in this thesis builds directly on this knowledge by investigating the role of microRNAs, a unique class of regulatory molecules that dynamically regulate gene networks and are capable of resolving seemingly paradoxical relationships between transcript and protein levels.Congruently, several of the leading microRNA gene networks that were identified by this objective targeted ESC/E(Z) transcripts.This thesis also uncovered evidence for a key role of the Vascular Epithelial Growth Factor A gene (VEGFA) in PMDD and began the foundational work of identifying transcriptional signatures of estradiol, progesterone, and allopregnanolone on human
Author: Allison Goff
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3195078142