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New discovery may help doctors treat infertility

July 21, 2005

New research suggests that medications commonly referred to as fertility drugs may be ineffective for women who lack a gene called the estrogen receptor beta. The study showed that fertility drugs did not improve ovulation rates in mice that were genetically engineered to lack estrogen receptor beta. The estrogen receptor beta is one of two estrogen receptor proteins which mediate the effects of estrogen hormones and are present throughout the female reproductive tissues. These new data indicate that this receptor plays a critical role in ovulation, and suggests that women who do not have this receptor may benefit more from alternative infertility treatments. The findings are reported in Endocrinology, published in August 2005.

"What we found is that the beta estrogen receptor plays a role in moving the egg outside the ovary so it can be fertilized," said Kenneth Korach, Ph.D., Laboratory Chief at the National Institute of Environmental Health Sciences (NIEHS) where the research was conducted. "We never knew before what function this receptor played in reproduction."

If the results from this animal study are found to be applicable to humans, a simple blood test will be able to provide enough information to determine if a genetic mutation may be altering the function of the estrogen receptor beta. The results of this blood test, coupled with information from other medical tests and evaluations conducted by the physician, will help diagnose infertility and better determine treatment options.

"Dealing with infertility can be emotionally, financially, and physically draining" said Dr. David Schwartz, Director of the NIEHS, a part of the National Institutes of Health, which funded the research. "If we can help couples understand the reasons for their infertility, doctors can further define their treatment options, help them to minimize the expense and risk of taking drugs that may be less effective for them, and increase their chances of having a safe and healthy child," he added.

The NIEHS researchers treated normal female mice and female mice that lack estrogen receptor beta with fertility drugs similar to those commonly used by women undergoing fertility treatments. The mice lacking this receptor are more likely to exhibit infertility or subfertility, including producing fewer offspring, or having less frequent pregnancies. Treatment with fertility drugs did not improve ovulation rates in these studies.

Years of study have shown that the hormone estrogen plays an important role in a variety of systems, most especially female reproduction. However, it was generally thought that there was only one receptor, the alpha receptor, that responded to estrogen. It wasn't until 1996 that the second receptor, estrogen receptor beta, was discovered. The current study provides evidence that the beta receptor plays a more significant role in ovarian function than the alpha receptor. Researchers would like to further their investigation into the role of the beta receptor by studying women already undergoing fertility treatment.

"The tools and animal models necessary to do these types of studies have only recently become available, but are already helping us to better understand the role of estrogen in the ovary," said John Couse, Ph.D., lead author of the August paper.

An earlier NIEHS study published in the June issue of Endocrinology, used a test tube or in vitro approach, to elucidate the role that estrogen receptors play in ovulation. "The combination of the two different methods, the in vivo and in vitro studies, complement each other nicely and provide more precise answers to the role that the estrogen receptor beta plays in ovulation," said lead author Judith Emmen, Ph.D.

The estrogen receptor beta is also known to respond to environmental and dietary chemicals that can mimic the effects of estrogen and stimulate the body's natural hormones. One example is genistein, a common component of soy products. These new studies by Korach and colleagues suggest that such environmental exposures could interact with estrogen receptor beta and possibly alter ovarian function in women.

NIH/National Institute of Environmental Health Sci