Document Type

Thesis

Date of Degree Completion

Spring 2020

Degree Name

Master of Science (MS)

Department

Biology

Committee Chair

April Binder

Second Committee Member

Lucinda Carnell

Third Committee Member

David Darda

Abstract

Polycystic ovary syndrome (PCOS) is the leading cause of infertility among women in the US and the most common endocrine disorder among women. PCOS is characterized by cystic ovaries, hyperandrogenism (heightened levels of male sex hormones), altered menstrual cycles and various metabolic dysfunctions. The metabolic symptoms associated with PCOS are difficult to treat, as they are a result of hormonal imbalances, rather than diet. The human Non-Steroidal Anti-Inflammatory Drug Activated Gene (NAG-1) been shown to prevent diet-induced metabolic disorders and weight gain in mice. We hypothesized that the expression of NAG-1 may also prevent hormonal-induced metabolic disorders. To test this question, we induced PCOS via dihydrotestosterone (DHT) implantation in transgenic mice expressing the human NAG-1 gene. Our findings suggest that NAG-1 mice have similar physiological responses to DHT-treatment as compared to wild-type mice throughout the 90-day study. Specifically no changes in the age of puberty and anal-genital distance (AGD) were observed. NAG-1 mice also display similar ovarian phenotypes, developing fewer corpora lutea, and having disrupted estrus cycles. NAG-1 mice displayed no significant weight gain between treatment groups throughout the study, and no significant increase in triglyceride levels. Additionally, NAG-1 mice showed no change in white adipocyte morphology after DHT-treatment. However, wild-type mice treated with DHT showed an increased amount of brown adipocytes differentiating to white adipocytes, compared to NAG-1 mice. Our findings indicate that NAG-1 mice respond similarly to DHT-treatment as wild-type mice in ovarian response, but continue to maintain their lean phenotype in the presence of induced PCOS. These findings suggest that expression of NAG-1 may have therapeutic benefits in the prevention of hormonal induced weight gain, and brown adipocyte hypertrophy.

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