Estrogen Insensitivity Syndrome And The Use Of Gene Therapy To Increase Height

Me: When I was reading through the PubMed articles yesterday there was a passage in one of the papers that seemed to provide an insight on an idea which I had for a long time. It deals with the possibility of decreasing either the number of function of the estrogen receptors one has in one’s growth plates.

The idea is that there have been three documented cases written up in articles which have been submitted to PubMed looking at males who have one specific gene mutation which have caused them to be insensitive to the effects of estrogen. They would go on to have unclosed epiphyseal plates even past into their 30s. two of them was recorded around the 6′ 8″ mark and they seemed to have normal body functions except one big issue, which is infertility. The medical experts even got them to use a type of estrogen/ cortisol mixture to help seal their growth plates and remove most of the other side effects from the gene mutation.

The idea that I had was that it might be possible to use vectors to target that specific cell area when the child still has their growth plates open, right after they have just started to hit the puberty growth spurt but also start developing their body into adult maturity. The sperm of the child (assuming the subject is male) can be collected for later while the treatment causes their growth plates to be open and make them as tall as desired. ONce they reach adulthood and have decided to stop growing, they can go back to the doctor for estrogen treatment to close the growth plates. Their problem on infertility can be solved by using the old sperm samples they have stored up for in vitro fertilization. This can also help people avoid unplanned pregnancies. 

It will be a good idea to read up on the wikipedia article on what exactly is estrogen insensitivity syndrome.

Estrogen insensitivity syndrome

From Wikipedia, (HERE)

The estrogen insensitivity syndrome (EIS) or estrogen resistance is a form of congenital estrogen deficiency[1] caused by a defective estrogen receptor(ER). Thus, estrogens cannot be recognized and initiate their biological action.[2]

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 theepiphyseal line, at risk for osteoporosis, and sterile (suggesting that in humans estrogens are necessary for reproduction).[3]

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.[4] ERKO mice show development of the respective female or male reproductive systems, 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 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.


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.

Tyler: Here’s a study I found that might be related.

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

“Estrogen exerts important effects in the skeleton, which are primarily mediated via estrogen receptor (ER)α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. Previous studies demonstrate that ERα ligands might act as agonists, partial agonists, or antagonists. ERα antagonist ICI 182,780 (ICI) acts in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. Importantly, ICI exerted a pronounced inverse agonistic activity in the growth plate of mice lacking ERαAF-2. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. ”

So can ICI increase height?

“The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. Ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. ”

So if you’re estrogen insensitive such that you lack AF-2 ICI(an ERalpha agonsit) can help you grow taller.

“the ICI–ERα complex is unstable, resulting in accelerated degradation of the ERα protein”

“ICI is used as an adjuvant endocrine therapy to treat ER-positive metastatic breast cancers in postmenopausal women with disease progression following the first line of antiestrogen therapy, as tamoxifen-as well as aromatase-resistant tumors might remain sensitive to ICI treatment”

“E2 reduced both the thymus weight (–73%) and the bone-marrow cellularity (–52%) in WT mice,whereas no effect of ICI was observed on these two parameters in WT or ERαAF-20 mice”

“The increase in growth plate height by ICI in the ovx ERαAF-20 mice resulted in an increased tibia and femur length (+4.2% and +2.8%, respectively) and was specific to the appendicular
skeleton, as neither the crown-rump length (axial skeleton) nor the total body weight was altered”

The increase in height by ICI was not due to altered IGF-1 levels.

ICI resulted in a slight, not statistically significant increase in femur and tibia length in wild type mice.

But some Estrogen receptors are constitutively active even when not binding so even if you don’t have estrogen, the estrogen receptors still decrease your height thus highlighting the purpose of inhibiting the estrogen receptors themselves with something like ICI.

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