a problem of sensitivity to estradiol · Inserm, Science for Health

Polycystic ovary syndrome is a common disorder that causes ovulation disorders, often accompanied by infertility. It manifests itself particularly through an accumulation of immature follicles in the ovaries. Scientists have just discovered it The These follicles are insensitive to estradiol, a locally produced hormone involved in their maturation and ovulation. It remains to be seen what the cause of this insensitivity is and may hold the key to new therapeutic solutions for patients.

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in women of childbearing age: 5 to 10% are affected. The disease is associated with excessive production of androgen hormones, especially testosterone, which leads to symptoms whose intensity varies from patient to patient: ovulation disorders leading to irregular cycles and infertility, excessive hair growth, hair loss, acne or even metabolic disorders such as bloating Obesity or diabetes. To date, however, the abnormalities of the endocrine system that cause this syndrome are poorly understood.

Recent work by Stéphanie Chauvin and her team Insert at the Paris Cité University nevertheless provided new insights into the mechanisms involved. As a specialist in estradiol receptors, the researcher wondered what role this hormone plays in the development of PCOS. As a reminder, ovarian follicles are structures composed of multiple layers of nourishing cells that contain rich fluid Growth factorsIn nutrientIn Metabolites or even in hormones in which an immature egg cell bathes. These follicles develop gradually to allow the maturation of this egg and its release (ovulation). This process depends in particular on estradiol: without this hormone, follicle development is interrupted and ovulation cannot take place. However, that is exactly what we see with PCOS: the disease is characterized by an accumulation of immature follicles in the patient’s ovaries.

A hormone that is produced but ineffective

Within the follicles, the local production of estradiol is ensured by the so-called “granulosa” feeder cells. The hormone is released into the follicular fluid, where it responds to the cells that produced it to promote follicular development. In addition, Stéphanie Chauvin’s team quantified this hormone at the follicle level and examined its effect on granulosa cells using samples taken from women with PCOS or not through a medically assisted reproductive process.

Several important observations were made. In women with PCOS, it appeared that estradiol is produced in normal amounts, but its concentration in the follicular fluid is lower than expected. “ Proteins responsible for protection the hormone are you too currently in smaller quantity. We assume SO that the hormone is further broken down this Women », explains Stéphanie Chauvin. Another important fact is that estradiol has no retroactive effect on the granulosa cells of patients with polycystic ovaries. While this hormone is thought to alter the expression of many genes involved in follicle development, this effect disappears in PCOS. “ Granulosa cells patients have estradiol receptors, but the intracellular signaling pathway is theoretically activated by this hormone appears clogged : The cells do not respond to the hormoneStéphanie Chauvin clarifies. We now need to find out whether this blockage occurs at the receptor level or further downstream. »

Anyway ” These results represent an advance in understanding the subtle mechanisms of the disease And show that exogenous intake of estradiol does not initiate follicle development. We need to find out why this hormone doesn’t work as expected THE follicles of Women with PCOS, try to develop new therapeutic approaches », concludes the researcher.

To learn more about polycystic ovary syndrome and its treatment, consult our file

Stéphanie Chauvin is an Inserm researcher on the team Physiology of the gonadotropic axis