The estrogen insensitivity syndrome (EIS) or estrogen resistance is a form of congenital estrogen deficiency

Congenital estrogen deficiency

Congenital estrogen deficiency is a genetic condition by which the body is unable to produce or use estrogens.Conditions include:* Aromatase deficiency, a condition where the enzyme aromatase is absent and androgens are not converted to estrogens....

 caused by a defective estrogen receptor

Estrogen receptor

Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...

 (ER). Thus, estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

s cannot be recognized and initiate their biological action.

In humans, the condition is very rare and only one case has been described. A reported male with EIS was tall as estrogens were unable to act to close the epiphyseal line

Epiphysis

The epiphysis is the rounded end of a long bone, at its joint with adjacent bone. Between the epiphysis and diaphysis lies the metaphysis, including the epiphyseal plate...

, at risk for osteoporosis

Osteoporosis

Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

, and sterile (suggesting that in humans 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 system

Reproductive system

The reproductive system or genital system is a system of organs within an organism which work together for the purpose of reproduction. Many non-living substances such as fluids, hormones, and pheromones are also important accessories to the reproductive system. Unlike most organ systems, the sexes...

s, and male and female alpha ERKO mice are infertile, beta ERKO males are fertile while females are subfertile, male and female double alpha and beta ERKO mice are sterile. The hypoplastic uterus

Uterus

The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

 does not respond to exogenous stimulation by estrogens. Males are infertile with atrophy

Atrophy

Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...

 in the testes. Bones age is delayed and bones are more brittle

Brittle

A material is brittle if, when subjected to stress, it breaks without significant deformation . Brittle materials absorb relatively little energy prior to fracture, even those of high strength. Breaking is often accompanied by a snapping sound. Brittle materials include most ceramics and glasses ...

. Variations in these patterns can be achieved by selectively disabling the alpha or beta ERs.

AIS

In contrast to EIS, the androgen insensitivity syndrome

Androgen insensitivity syndrome

Androgen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...

 (AIS) where the androgen receptor

Androgen receptor

The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...

 is defective is relatively common. This can be explained by the genetics of each syndrome. AIS is a X-linked recessive

X-linked recessive

X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...

 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

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 and is not transmitted to offspring.

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

Aromatase

Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...

.