Endocrine Abstracts

Evan Simpson, Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia Abstract

Professor Simpson is generally recognised as a world leader in the area of oestrogen biosynthesis. His lab was the first to clone the cDNA and subsequently the human gene encoding aromatase, the enzyme responsible for oestrogen biosynthesis. They were the first to show that tissue-specific regulation of this gene is mediated via alternative promoters which are expressed in a tissue-specific fashion. This is of great consequence because in men and in postmenopausal women, most of the oestrogen synthesised is in extragonadal sites such as breast, bone, brain, vascular smooth muscle etc., and because of the unique promoter structure, regulation of oestrogen biosynthesis in each of these sites is different, thus allowing for tissue-specific intervention by drug therapies e.g. in breast cancer treatment. The lab was also the first to develop a mouse model of oestrogen insufficiency by targeted disruption of the aromatase gene. The various phenotypes that emerged are duplicated in human beings with natural mutations of the aromatase gene, and have led to new insights into the physiological and pathophysiological roles of oestrogen in both males and females.