Genes and infertility

15 July 2003

Scientists funded by the Wellcome Trust have found one of the causes of a disease that leads to infertility, miscarriages and obesity in thousands of women. Polycystic ovary syndrome (PCOS) can also cause excessive hair growth and irregular periods, and is believed to affect between 5 and 10 per cent of pre-menopausal women in England and Wales. It is caused by overproduction of male hormones in females.

Working at the Queen Elizabeth Hospital Wellcome Trust Clinical Research Facility, Professor Paul Stewart and colleagues at the University of Birmingham have discovered the genetic basis of a hormone disorder in three individuals with PCOS-like symptoms. Each of the three patients had mutations in two genes affecting the cortisol-cortisone hormone system, which led to reduced levels of cortisol - and consequent overproduction of male hormones.

One of the genes is involved directly in the conversion of cortisone to cortisol (HSD11B1, encoding the enzyme 11bhydroxysteroid dehydrogenase). The second (H6PDH, encoding hexose-6-phosphate dehydrogenase) has a more subtle role, affecting the production of an essential factor which ensures that the chemical conversion goes in the correct direction - that cortisone is converted to cortisol rather than vice versa.

Combined mutations in the two genes are likely to be rare, but more research will be needed to determine how common related mutations are in PCOS patients. In addition, abnormalities in the cortisol-cortisone pathway could be involved in other common metabolic disorders, and studies of the possible role of H6PDH in these conditions is now eagerly anticipated.

The results were published in Nature Genetics, 13 July 2003 (Vol. 34: 434-9).

See also

• Infertility breakthrough (Press release: 13 July 2003)

External links

• Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency, Nature Genetics 34, 439-9 (13 July 2003)
• Professor Paul Stewart at the Queen Elizabeth Hospital, University of Birmingham (Research details)