Childhood obesity has been blamed for a number of medical conditions affecting too many American children. Researchers at the University of Virginia School of Medicine have received a $7 million U54 Center Grant from the National Institutes of Health (NIH) to examine yet another condition believed to be related to obesity-Polycystic Ovary Syndrome (PCOS). The condition is on the rise among young women, causing them hormonal imbalances that lead to infertility, male-pattern hair growth, metabolic syndrome, and an increased risk of developing diabetes and coronary artery disease in mid-life.
Past animal studies have shown that a female fetus exposed to too much male hormone in the womb will show changes in puberty that are similar to those seen in women with PCOS. According to John C. Marshall, MD, professor of internal medicine and director of the Center for Research in Reproduction, high levels of male hormones are present in girls who are obese. The goal of Marshall’s team is to learn how to normalize those levels in girls so that they can have a normal journey through adolescence and ultimately avoid PCOS in early adulthood.
“We already know that signals coming from the brain and the pituitary gland to the ovaries are abnormal in girls with too much testosterone,” says Marshall. “Now we have to prove that the high levels of testosterone are present before puberty and if these high levels affect the way girls go through puberty. Then we hope to learn how to prevent it from occurring.”
Marshall’s research collaborators include Margaret Shupnik, PhD, professor of endocrinology and molecular physiology and biological physics; Suzanne Moenter, PhD, professor of endocrinology; Dan Haisenleder, PhD, associate professor of research; and Christopher McCartney, MD, assistant professor of research.
Marshall and McCartney both have clinical projects funded by the grant, which investigate brain signaling to the ovary in adolescent girls and the ovarian response in terms of hormone production. Moenter studies mechanisms by which the brain signaling gonadotropin-releasing hormone (GnRH) neurons are regulated by the central nervous system and by external influences such as plasma steroid hormones and insulin. Shupnik investigates the effect of the changes in plasma steroids on pituitary gland responses to GnRH, producing the two pituitary hormones LH and FSH that control the ovaries.
The NIH U54 Center Grant is an institutional award given to a principal investigator and is distributed over a five-year period. The Center grant awarded to Marshall and his team also provides funding for a Ligand Assay and Analysis Core which serves as a national resource to other NIH U54 Centers throughout the country.
“This grant was a very generous gift, and we are very fortunate that the review groups at the NIH considered these studies worthy of funding for the next five years,” Marshall says.