Researchers at the University of Wisconsin, Madison have found that in order for ovulation to occur in monkeys, estrogen must be produced in the brain. The work was published earlier this week in Proceedings of the National Academy of Science.
The hypothalamus in the brain stimulates cells in the pituitary gland, which then causes the ovaries to produce a hormone called estradiol, a type of estrogen. Estradiol builds in the bloodstream until it reaches a concentration that causes a surge of the hypothalamic and pituitary hormones, including one called luteinizing hormone, which in turn trigger an ovary to release an egg.
"It's a feedback loop, and scientists have thought for some time that it was all to do with the estrogen from the ovaries," says Ei Terasawa, professor of pediatrics at the UW-Madison School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. "Then, in 2013, we discovered the hypothalamus was releasing estradiol like the ovaries, and we were so surprised. We knew it had to be important."
To figure out what this important role could be, Terasawa, Brian Kenealy and colleagues implanted capsules under the skin of rhesus macaque monkeys. In addition, they also prevent the production of estrogen from the monkeys themselves using an enzyme called aromatase.
The researchers saw that the rising release of luteinizing hormone began, but fell short of the full surge required to spark ovulation by about 70 percent compared to animals whose estrogen production wasn't suppressed.
To take a closer look, the researchers repeated the process but blocked estradiol production specifically in the hypothalamus in the monkeys. They looked for the emergence of hypothalamic hormones, gonadotropin-releasing hormone and kisspeptin, which were indicators that the key neurons were ramping up to cue the luteinizing hormone surge.
However, this time, all three ovulation-signaling hormones were reduced. This indicated that the brain was where the estradiol effects were happening.
"The ovarian estrogen starts the surge, but the brain estrogen allows the surge to continue," says Kenealy. "When we block the production of brain estrogen, we still start the surge, but basically we cut the top off the mountain and the surge is drastically reduced."
"This shows the brain's estrogen is a huge helper, necessary for the release of an egg that makes pregnancy possible," says Terasawa.
Kenealy notes that their work fills in some of the gaps of knowledge they didn't know before and will help people in the future in regards to fertility issues.