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Scientists Detect Key Proteins Needed for Ovulation

Unfertilized human egg sitting on the point of a pin. Yorgos Nikas. All rights reserved by Wellcome Images

Researchers have identified 2 proteins that are essential for ovulation in mice. The finding has implications for treating infertility and may also offer new options for preventing pregnancy by blocking release of the egg.

Ovulation-the release of a mature egg from an ovary-results from a complex series of biochemical events. Each month, prompted by hormones, the immature egg and the protective follicle that surrounds it grow and develop. Midway through a woman's monthly cycle, the pituitary gland releases a surge of luteinizing hormone, which causes the egg to mature and the follicle to burst open, releasing the egg. The primary cells in the follicle, called granulosa cells, then transform into luteal cells, which produce progesterone to continue the reproductive cycle.

Previously, scientists were uncertain how luteinizing hormone manages to trigger egg maturation, ovulation and the creation of progesterone-secreting cells. Some studies have hinted that 2 proteins, called extracellular-regulated protein kinase 1 and 2 (ERK 1 and 2), play a role in the ovulatory process. These enzymes are known to act as signaling molecules that help to direct cell division and other activities throughout the body. To learn more about their function, Dr. JoAnne S. Richards of Baylor College of Medicine and her colleagues created genetically altered mice that lacked ERK 1 and 2 in the ovary's granulosa cells. Their work was funded in part by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Cancer Institute (NCI).

In the May 15, 2009, issue of Science, the researchers reported that the altered mice were able to produce eggs in their ovaries, but the eggs did not mature and were not released after exposure to luteinizing hormone. Moreover, the granulosa cells didn't transform into luteal cells and begin producing progesterone.

Further analysis suggested that luteinizing hormone normally binds to granulosa cells and signals the release of ERK 1 and 2. These enzymes, in turn, trigger gene activation and a chain of chemical events that ultimately lead to the maturation and release of the egg, the transformation of granulosa cells into luteal cells and the production of progesterone. Disrupting the ERK 1 and 2 genes completely derails the ability of luteinizing hormone to stimulate these important events.

“The researchers have identified a crucial biochemical intermediary controlling the release of the egg,” says NICHD Director Duane Alexander. “The finding advances our understanding of the ovulatory process and may one day contribute to new treatments for infertility as well as new ways to prevent pregnancy from occurring.”