Tag Archives: PCOS

Investigating the role of the androgen receptor in polycystic ovarian syndrome

Research Project

For the past summer, I have been working in laboratory of Dr. Sheng UW at the Johns Hopkins School of Medicine. In the Wu lab, we are investigating the etiology of polycystic ovarian syndrome or disease (PCOS/PCOD). One of the major clinical presentations of PCOS is high levels of androgens, a condition known as hyperandrogenism, and the Wu lab focuses on the androgen receptor (AR) which binds to androgen outside of cells and acts inside the cell to express certain genes. The mouse model that we use mimics hyperandrogenism by exposure to dihydrotestosterone (DHT), which is present in low amounts in women without PCOS. To investigate mechanisms of hyperandrogenism and the AR, knockout mice without the receptor are compared to control mice, enabling us to investigate the effects of differential levels of DHT and the role of the AR on fertility, gene expression, protein and RNA levels, adipose tissue, and ovarian morphology (Wu et al., 2014). Despite the prevalence of PCOS in women of reproductive age, and its association with metabolic dysfunction, infertility and hirsutism, the exact cause is not known and effective treatment options are not available. By elucidating the pathophysiology of PCOS, treatment can be designed to target the cause as opposed to only clinically managing the symptoms temporarily.

Realities of Research

Although the prospect of doing research in a lab might sound like it involves the use of expensive equipment and the newest technology (and in many cases this is very true), a large portion of research involves spending hours maintaining and genotyping new litters, waiting for assays and reactions to finish, and pipetting hundreds of samples. Experiments sometimes work, and at other times they fail and must be repeated. Small errors in pipetting or mindlessly forgetting to include a certain solution can cause time-consuming experiments to fail. But, the most critical learning experiences I have had thus far were assessing what went wrong and fixing it by. Results are also not immediate; it takes several weeks before the effects of DHT can be assessed. Confirming the genotypes of our mice is critical to make sure that we are investigating what we claim to be, and ensuring DHT surgeries are done at the correct time requires attention and organization. Preliminarily, the effects of DHT we have observed have been physiologically plausible, although much of the data collection of the study is still ongoing.

Life of a Scientist

Simultaneously, the best and worst parts about doing research in a lab are that the hours are flexible and I can plan my week. But, this also means spending evenings working due to long wait times for experiments that extend past the usual 9 to 5 working day, or because a protocol calls for a certain experiment to be done at a certain time. The independence is exciting, but can also be intimidating as I must be aware of what needs to be done and when. However, research is collaborative. As the youngest and most inexperienced person in my lab, I am always learning how to do new experiments and how to interpret and analyze data. Others are always offering me tips and tricks, supporting me when I fail, and helping me deal with my constant fear of getting bitten by mice. The most rewarding moments of the summer so far have been presenting data to my PI and co-PI, and teaching members of the lab how to complete a computerized tissue analysis that had not been done in our lab before. The most disappointing? Waking up early to complete a western blot protein analysis only for it to fail – not once, but multiple times!

References:

  1. Wu, S., Chen, Y., Fajobi, T., DiVall, S., Chang, C., Yeh, S. and Wolfe, A. (2014). Conditional Knockout of the Androgen Receptor in Gonadotropes Reveals Crucial Roles for Androgen in Gonadotropin Synthesis and Surge in Female Mice. Molecular Endocrinology, 28(10), pp.1670-1681.
Gopika Punchhi is a rising senior at Johns Hopkins University in Baltimore, MD, pursuing degrees in Molecular and Cellular Biology and Public Health Studies. Through the Undergraduate Summer Research Fellowship (UGSRF) program, she is spending the summer working under Sheng Wu, PhD, an associate professor in the department of Physiology at the Johns Hopkins School of Medicine. UGSRF is funded by the APS. Gopika plans on attending medical school to become and gynecologist or endocrinologist, while also continuing involvement in molecular and population-level research in these fields.