Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women in their reproductive age. Based on the Rotterdam criteria PCOS is defined by two out of the following three criteria: hyperandrogenism, oligo/anovulation, and polycystic ovaries. In addition, PCOS patients are often abdominal obese, which can lead to insulin resistance. The subsequent increased insulin levels stimulate the ovary to further increased androgen production. Thus, the elevated androgen and insulin levels may result in a detrimental vicious circle between ovary and adipose tissue. Our aim was to develop a mouse PCOS-like model, allowing the future use of transgenic mouse models to study the interaction between ovarian and adipose function in PCOS.

Prepubertal female mice received a 60 or 90 days continuous release pellet containing the non-aromatizable androgen dihydrotestosterone (DHT) or vehicle. At the end of the treatment period the estrous cycle was analyzed and ovaries were collected. Furthermore, body weight was measured, fat depots were morphologically analyzed and an intraperitoneal glucose tolerance test (IPGTT) was performed.

DHT treatment for 60 days did not result in differences in reproductive and metabolic characteristics compared to vehicle-treated mice. In contrast, 90 days DHT-treated mice were in continuous an-estrous and their ovaries lacked corpora lutea, consistent with anovulation. Antral follicles of 90 days DHT-treated mice had a cyst-like structure and there was an increase in the number of atretic follicles. These mice also showed a significantly higher body weight. In addition, fat depots of DHT-treated mice displayed an increased number of adipocytes of increased size. Furthermore, blood glucose levels during IPGTT were higher, suggesting that these mice are glucose intolerant.

We conclude that DHT treatment for 90 days in mice results in a metabolic and reproductive phenotype resembling the phenotype found in PCOS women.