Monday, March 31, 2014
Researchers from Penn State College of Medicine and Virginia Commonwealth University School of Medicine have found that a specific protein is increased in theca cells, the source of excess male sex hormones, or androgens, that characterizes polycystic ovary syndrome (PCOS). The results of the study will be published in an upcoming issue of the Proceedings of the National Academy of Sciences of the United States of America (PNAS) as the journal cover article. The paper will be available in this week’s online Early Edition.
PCOS is a common disease affecting 7 percent of reproductive-aged women worldwide. Symptoms of PCOS include increased male sex hormone levels, which cause hirsutism and acne; infertility due to the failure to ovulate; and enlarged ovaries with follicle cysts. In addition, obesity and diabetes are often associated with PCOS.
“There is a consensus that theca cells of ovarian follicles are the primary source of excess androgens that characterizes PCOS,” said Jan M. McAllister, Ph.D., lead author of the study and professor of pathology and obstetrics and gynecology at Penn State College of Medicine.
Studies conducted over the past decade have built a convincing argument that genetic factors contribute to PCOS. However, despite advances in genetic technologies, few if any PCOS susceptibility genes have been validated. The current study found that an alternative product of the DENND1A gene, DENND1A.V2, is increased in PCOS theca cells.
McAllister noted, “Prior to our studies, there was no pathophysiological link between DENND1A to reproduction or ovarian function. Our observations suggest that DENND1A is involved in a signaling cascade that subsequently results in increased androgen production.”
The study showed that raising DENND1A.V2 in normal theca cells increases the expression of genes that lead to elevated androgen production. It also found that silencing DENND1A.V2 in PCOS theca cells reverts them to a normal phenotype.
“Our findings establish that increased DENND1A.V2 expression is sufficient to promote a PCOS phenotype in human theca cells,” said Jerome F. Strauss, M.D., Ph.D., senior author of the study and dean of the VCU School of Medicine. “This information can inform development of diagnostic tests for PCOS based on measurements of DENND1A.V2, and may one day lead to novel therapeutic interventions, including drugs or antibodies that neutralize the action of DENND1A.V2.”
This is one of the first published studies following an informal agreement signed by the two universities to work closely together on health research with the common goal of moving important findings from the lab to the clinic and community more efficiently.
The memorandum of understanding signed by Penn State and VCU in fall 2013 is built around the National Institutes of Health’s Clinical and Translational Science Award (CTSA). The two institutions are among 62 academic research centers in the nation to receive CTSAs, which are intended to spur collaboration around scientific health discoveries.
About VCU and VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 226 degree and certificate programs in the arts, sciences and humanities. Sixty-seven of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.
About Penn State and Penn State Milton S. Hershey Medical Center
Penn State is a multi-campus public research university that educates students from Pennsylvania, the nation and the world, and improves the well-being and health of individuals and communities through integrated programs of teaching, research, and service. For more, see www.psu.edu. Founded in 1963 through a gift from The Milton S. Hershey Foundation, Penn State Milton S. Hershey Medical Center is a leading academic medical center located in Hershey, Pa. The Medical Center campus includes Penn State College of Medicine (Penn State’s medical school), Penn State Hershey Cancer Institute, and Penn State Hershey Children’s Hospital—the region’s only children’s hospital. For more, see www.pennstatehershey.org.