P450 oxidoreductase: Novel regulator of steroid synthesis and metabolism in health and disease

人肾上腺产生激素脱氢表雄酮（DHEA），其是男性和女性中产生雄激素（即活性雄性激素）的主要前体。过多的雄激素会导致女性月经不调、不孕、痤疮，并增加患糖尿病和高血压的风险，概括为多囊卵巢综合征。这种情况影响到所有妇女的5-10%。我们已经发现了两种新的机制，分别调节DHEA的生产和分解。具有突变的患者，即其遗传密码中的一个小的拼写错误，影响我们已经确定的两个因素之一，POR和PAPSS 2，患有雄激素过多。我们的研究旨在找出POR和PAPSS 2的破坏导致雄激素过多的机制。POR和PAPSS 2在调节肝脏中药物和激素代谢方面也起着重要作用，因此我们的研究也将为这些机制提供重要见解。阐明这两种新的调节途径在人类生理学和疾病中具有明确的翻译潜力，即有可能将新知识应用于新疗法的开发。

The human adrenal gland produces the hormone dehydroepiandrosterone (DHEA), which is a major precursor for the production of androgens, i.e. active male hormones, in both men and women. Too much androgen in women can cause irregular periods, infertility, acne and increases the risk to diabetes and high blood pressure, summarised by the term polycystic ovary syndrome. This condition affects 5-10% of all women. We have discovered two novel mechanisms that regulate the production and the breakdown, respectively, of DHEA. Patients who have a mutation, i.e. a small spelling error in their genetic code, affecting one of the two factors we have identified, POR and PAPSS2, suffer from androgen excess. Our research will aim to find out by what mechanisms disruption of POR and PAPSS2 causes androgen excess. POR and PAPSS2 also play an important role in regulating the metabolism of drugs and hormones in the liver and thus our research will also give important insights in these mechanisms. Clarification of these two novel regulatory pathways in human physiology and disease carries clear translational potential, i.e. comes with the possibility of applying new knowledge to the development of novel therapies.