A genetic receptor mutation that blocks the action of estrogen has been discovered for the first time in a female, according to a report published in the New England Journal of Medicine.
The 18-year-old woman was showing classic symptoms of having lower estrogen levels than normal after experiencing no breast development or menstruation. But researchers at Augusta's Medical College of Georgia found that the female had extremely high levels of estrogen in her blood.
Dr. Lawrence Layman, head of reproductive endocrinology, infertility and genetics at the medical school, said: "Her body totally ignores estrogen. Even at levels that are 10 to 15 times normal, it has no effect."
Dr. Layman adds that in laboratory studies, it took 240 times the normal level of estrogen to gain a response from the woman's receptor.
There are two types of estrogen receptor that have been confirmed by research, the authors point out: estrogen receptor-alpha, and estrogen receptor-beta.
Genetic testing revealed that this woman had a mutation in estrogen receptor-alpha, the type essential for bone health and reproduction, the researchers say. They add that the estrogen levels in her blood were as low as those seen in research mice whose receptor-alpha genes have been removed.
Woman's body was unable to have a normal menstrual cycle
The researchers explain that the woman's defected estrogen receptor is "unable to use the estrogen within her body, control how much of it is made or control its result." They explain that the woman had cystic ovaries because her body was in continual production of follicles, when usually the body provides just one a month as part of the menstrual cycle.
Samuel D. Quaynor, the study's first author, explained that it is estrogens binding with the receptor that activates the negative feedback system, telling the brain that there is a lot of estrogen, but this was not happening in the woman.
In the report, the researchers speak of the first discovery - but in a man - of a mutated estrogen receptor, in a 28-year-old man almost 20 years ago. The man was suffering from knock-knees, an abnormal curvature of the legs, and signs of insulin resistance.
The study about the man published in the New England Journal of Medicine by researchers at the Children's Hospital Medical Center in Cincinnati, revealed that although his testosterone levels were high, as well as his estrogen and related hormone levels, he also had no response to estrogen. The research team concluded that the man had an estrogen receptor defect, and that estrogen is "important for bone maturation and mineralization" in both men and women.
In this most recent study, researchers point out that without estrogen, insulin levels will increase, resulting in a higher risk of diabetes - which was a consequence for the man with the mutated estrogen receptor. However, the woman's glucose and insulin levels were normal, although the authors note that her oral glucose test did suggest a future risk of diabetes.
The researchers would now like to do more to fully understand the impact of the receptor mutation. They hope to carry out large-scale screening to see if other substances bind to the altered receptor.