Estrogen insensitivity syndrome

The estrogen insensitivity syndrome (EIS) is a form of congenital estrogen deficiency caused by a defective estrogen receptor (ER). Thus, estrogens cannot be recognized and initiate their biological action.

In humans, the condition is very rare and occurs sporadic. Only a few cases have been described. A reported male with EIS was tall as estrogens are not present to close the epiphyseal line, at risk for osteoporosis, and sterile (suggesting that estrogens are necessary for reproduction).

ERKO mice
Estrogen insensitivity syndrome of can be experimentally induced in animals, typically mice, by knocking out the estrogen receptor. In so-called ERKO mice different estrogens receptors can be disabled allowing to study the role of such receptors. ERKO mice show development of the respective female or male reproductive systems, and are sterile if both, alpha and beta estrogen receptors are defective. The hypoplastic uterus does not respond to exogenous stimulation by estrogens. Males are infertile with atrophy in the testes. Bones age is delayed and bones are more brittle. Variations in these patterns can be achieved by selectively disabling the alpha or beta ERs.

AIS
In contrast to EIS, the androgen insensitivity syndrome (AIS) where the androgen receptor is defective is relatively common. This can be explained by the genetics of each syndrome. AIS is a X-linked recessive condition and thus carried over into future generations. EIS is not compatible with reproduction, thus each occurrence in humans would have to be a de-novo mutation and is not transmitted to offspring.

Congenital estrogen deficiency can also be caused by a defect in the aromatizing enzyme.