The Hormonal Regulation of the Claudin Genes in the Ovary

The ovary is a dynamic organ that responds to many hormonal signals. When these hormonal signals are disrupted, ovarian dysfunction can occur. One such example is Polycystic Ovarian Syndrome (PCOS). PCOS patients suffer from high levels of testosterone. Excess testosterone may misregulate genes in the ovary and disrupt ovarian function. The Claudin (<em>Cldn</em>) 3 and <em>Cldn11</em> genes have been shown to be regulated by androgens in the testis, while studies in ovarian cancer cells suggests a coregulatory mechanism for the expressions of <em>Cldn3</em> and <em>Cldn4</em> in the ovary. The objective of this study was to characterize the hormonal regulation of <em>Claudin</em> gene expression in the ovary. The ovaries of estrogen receptor alpha knockout (αERKO) mice have high serum testosterone concentrations, therefore <em>Claudin </em>expression was measured in these ovaries. Experiments were conducted using Quantitative Real Time PCR (QRT-PCR) to monitor the expression of <em>Cldn3</em>, <em>4</em>, and <em>11 </em>in wild-type (WT) and αERKO mouse ovaries. These experiments indicated that <em>Cldn3</em>, <em>4</em>, and <em>11 </em>were more highly expressed in αERKO mice than their wild-type counterparts (p < 0.05, n = 5). Further experiments characterized Claudin<em> </em>expression in the ovaries of mice treated with Dihydrotestosterone (DHT) for 90 days which serve as a common mouse model of PCOS. DHT treated mice were found to express <em>Cldn3 </em>and <em>Cldn11</em> significantly higher than control mice.<em> Cldn4</em> expression decreased in DHT treated mice when compared to the controls (p < 0.05, n = 4 for control and DHT groups). These findings indicated that<em> Cldn3</em> and <em>Cldn11</em> are upregulated by testosterone in the ovary. The data also indicates<em> Cldn4 </em>is regulated via different mechanisms than the other Claudin genes in the mouse ovary. DHT reduces expression of <em>Cldn4</em>, while increases are observed in the absence of ERα. Claudin expression was also evaluated in the ovaries of mice that were treated with testosterone propionate (TP) for three or six days. No expression of <em>Cldn3</em> or <em>Cldn11</em> was found, however <em>Cldn4 </em>steadily increased in conjunction with the duration of the testosterone propionate treatment. Western blot analysis for the presence of CLDN3 in the ovaries of control and TP treated mice yielded no detectable signal for either group.<em> </em> Studies done in cell lines found that<em> CLDN4</em> expression decreased when BG-1 ovarian epithelial cells were treated with testosterone. These findings provide a first consider the regulation of the Claudin genes in the ovary, while providing a basis for future research to explore how they may contribute to PCOS.

Name thesis:degree_name

Master of Science (MS)

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2016

Authors dc:creator

• Gadson, Sean
• Binder, April
• Korach, Kenneth
• Hamilton, Katherine

Contributors dc:contributor

• April K. Binder
• Lucinda Carnell
• Holly Pinkart

• PCOS
• Polycystic Ovarian Syndrome
• Claudin
• Expression
• Endocrine System Diseases
• Female Urogenital Diseases and Pregnancy Complications
• Genetic Processes
• Medical Pathology
• Physiological Processes
• Reproductive and Urinary Physiology

Language dc:language

English

Repository record dc:identifier

https://digitalcommons.cwu.edu/etd/540

OAI identifier oai:identifier

oai:digitalcommons.cwu.edu:etd-1544