Estrogen Receptor Alpha May Be Involved in Development of Cushing’s During Pregnancy

Estrogen receptor alpha — one of the two main types of protein receptors activated by the female sex hormone estrogen — likely is involved in the development of Cushing’s syndrome during pregnancy.

The study with that finding, “Estrogen receptor α plays an important role in Cushing’s syndrome during pregnancy,” was published in the journal Medical Hypotheses.

Cushing’s syndrome is caused by the excessive production of the glucocorticoid hormone cortisol by the adrenal glands, which sit atop the kidneys.

In 60–70% of the cases, the disorder is caused by the excessive production of the adrenocorticotropic hormone (ACTH) driven by a tumor in the pituitary gland or elsewhere in the body. However, in approximately 25% of the cases, it may be caused by tumors in the adrenal glands that produce too much cortisol.

Although Cushing’s syndrome is rarely seen during pregnancy, when it occurs it may lead to complications for both the mother and the developing fetus.

“[T]he fetal mortality is as high as 25–40% due to spontaneous abortion, stillbirth and prematurity. Therefore, a high degree of clinical awareness is required to recognize CS [Cushing’s syndrome] and to avoid maternal and fetal complications,” researchers wrote.

In most cases described in the literature to date, the disease in pregnant women seems to be caused by tumors in the adrenal glands, and in some women it can resolve spontaneously following delivery or spontaneous abortion.

“These observations suggest that adrenal hyperfunction should be associated with some elevated product or hormones during pregnancy. However, the specific mechanisms of CS during pregnancy remain unclear,” researchers wrote.

Here, investigators at Shandong University, in China, hypothesized that estrogen receptor alpha (ER alpha) probably is involved in the development of Cushing’s syndrome during pregnancy.

ER alpha can be found in the adrenal glands, as well as in adrenal tumors. It also is known to be involved in the production of cortisol by the adrenal glands. Some studies have indicated that, when active, ER alpha may stimulate the development of adrenal tumors.

Hormonal changes during pregnancy result in an increase in the production of estrogen — the female sex hormone that is able to interact and activate ER alpha.

So, it is possible that high levels of estrogen during pregnancy lead to an excessive activation of ER alpha in the adrenal glands and/or adrenal tumors, resulting in an excessive production of cortisol accompanied by tumor development.

“ER [alpha] is involved in the adrenal cortisol production and adrenocortical tumorigenesis, suggesting that ER [alpha] may play an important role in the pathogenesis [development] of CS during pregnancy,” the researchers wrote.

“Definition of the mechanism involved may eventually lead to biologic insights and potential improvements in diagnosis and treatment for CS during pregnancy,” they concluded.