A receptor mutation that essentially blocks estrogen’s action has been identified for the first time in a female, researchers report.
The 18-year-old wasn’t experiencing breast development or menstruation, classic symptoms of too little estrogen, the usual cause of delayed puberty. Subsequent studies revealed instead sky-high levels of the sex hormone in her blood, said Dr. Lawrence C. Layman, Chief of the Section of Reproductive Endocrinology, Infertility and Genetics at the Medical College of Georgia at Georgia Regents University.
“Her body totally ignores estrogen,” Layman said. “Even at levels that are 10 to 15 times normal, it has no effect.” In fact, in laboratory studies, 240 times the normal level was required to get a response out of the receptor.
There are two confirmed estrogen receptors, and genetic testing subsequently determined she had a mutation in estrogen receptor-α, which is essential to reproduction and bone health, researchers report in the New England Journal of Medicine. Estrogen levels in her blood were comparable to those of a mouse whose estrogen receptor-α gene has been deleted.
Interestingly the first mutation in this receptor was reported nearly 20 years earlier in the NEJM in a 28-year old man with knock-knees and signs of insulin resistance. Studies showed his testosterone levels were normal and, although his estrogen and related hormone levels were high, he also had essentially no response to estrogen. The research team, led by Children’s Hospital Medical Center in Cincinnati, found the estrogen receptor defect, concluding that estrogen is important to bone health in men as well as women.
- Published in Genetics and Birth Defects