Hormones play an important role in mammalian reproduction. So when something goes wrong with them, a lot of other things can go wrong too. A University of Wyoming researcher is trying to figure out exactly what role misregulation of the hormones estrogen and progesterone play in female reproductive diseases like endometriosis, which affects one in ten women.
Jim Pru is a professor and the Rochelle Chair in the Department of Animal Science. His lab turns genes, which are responsible for the production and regulation of hormones, off and on one at a time in special "knockout mice" to learn what they do. A knockout mouse is a term for a genetically modified mouse that has a gene inactivated or "knocked out" by an artificial piece of DNA. They are important animal models for studying the role of genes that have been sequenced but whose functions haven't been determined yet.
According to Pru, their findings in mice should be applicable to all mammals, regardless of size or species.
"The focus in my laboratory is on genes that are evolutionarily conserved. In other words, the genes that are found to be important, or at least thought to be important, in a number of different mammalian species," said Pru. "If we show that a gene is important, then it has application to women and to large animals, like pigs and horses and sheep and cows."
Progesterone prepares the uterus for early embryo implantation and then helps maintain the pregnancy.
"So the progesterone is really important for normal fertility in all mammals, and when that signaling mechanism either decreases or alters production of progesterone or the ability of reproductive tissues like the uterus to respond to progesterone and [they] become dysfunctional, then we have infertility issues," said Pru.
Pru's lab was the first to study a family of genes known as the progesterone receptor membrane component (PGRMC) family, which mediates some of the actions of estrogen and progesterone.
"These mutations in the PGRMC-1 gene cause all sorts of issues everything from cancer to a number of women's reproductive diseases, such as endometrial cancer, early menopause, there's a condition called premature ovarian insufficiency, endometrial cancer. Endometriosis is another common disease in women," he said. "And we know that women with endometriosis have issues with the expression of this PGRMC-1 gene in the uterus."
Pru hopes the research in his lab can be used to help design therapies for individuals with diseases caused by these misregulations.
"If we understand which genes are important when they become abundantly expressed or mutated in developing endometrial cancer or endometriosis, then we can design therapies to target those genes," Pru said.
