By mutating the aromatase enzyme so it can no longer function, our Group has developed a mouse that is incapable of producing any oestrogen. This has given us enormous insight into the role of oestrogen in the body, and revealed unexpected functions in both males and females.

The Aromatase knockout or ArKO mice accumulate significant amounts of abdominal fat, causing obesity and diabetes. Men and postmenopausal women tend to develop this upper body distribution of fat, which is associated with a greater risk of insulin-resistant diabetes, cardiovascular disease and breast cancer. The mice also suffer from increased cholesterol and fat in their blood, as well as in their livers. Even more significant, the administration of oestrogen leads to a dramatic decrease in fat accumulation, such that the ArKO mice end up leaner than the control animals. The ovaries of the female ArKO mice are grossly impaired and contain structures which are very similar to those found in the testis, namely cells known as Sertoli cells.

Studies with the male ArKO mouse have shown that their gonads are also affected by a lack of oestrogen. They are infertile and in fact, there is a significant block to sperm production, suggesting that oestrogen is not always a ‘female’ hormone as previously thought, but necessary for reproduction in both sexes. Further studies have found that the sexual
behaviour of the mice is affected as well, since the male ArKO mice are unable to even mount the females in order to reproduce and are generally much less aggressive than normal male mice. It is expected that further studies will reveal more of the roles of this important hormone in both sexes.