Evan Simpson‘s research group were the first to clone the gene encoding aromatase, the enzyme responsible for oestrogen biosynthesis, and to show that tissue-specific regulation was under the control of tissue-specific promoters. In post-menopausal women, oestrogen action in breast, brain and bone is due to local production in these respective sites. New therapies for breast cancer prevent the formation of oestrogen in the breast – where it is implicated in cancer development – but would spare it in sites such as bone, brain and blood vessels, where it has important functions. Evan's group also generated a mouse in which the aromatase gene is inactivated. The mouse exhibits a range of symptoms: infertility and lack of libido in both sexes; loss of bone mineralisation in both sexes; cardio- and cerebro-vascular defects; a Metabolic Syndrome including obesity, fatty liver and insulin resistance; and behavioural defects including compulsive traits. Many of these symptoms are also found in humans with inactivating mutations in the aromatase gene. Thus estrogens have a variety of roles in both males and females, some of which have nothing to do with reproduction, and some of which were quite unexpected.

Oestrogens – the good, the bad, and the unexpected
by Professor Evan Simpson

Models of oestrogen insufficiency have revealed new and unexpected roles for estrogens in both males and females. These models include natural mutations in the gene encoding aromatase, the enzyme responsible for oestrogen biosynthesis, as well as mouse knock outs of aromatase and the oestrogen receptors. Many of these roles apply equally to males and females – for example, loss of fertility and libido – but also bone loss, cardio- and cerebro-vascular defects, obesity, insulin resistance and the Metabolic Syndrome. Thus oestrogens are involved in many aspects of physiology in both sexes.

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