Hillier Stephen G
The Queen's Medical Research Institute, Centre for Reproductive Biology, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
J Endocrinol. 2007 Oct;195(1):1-6. doi: 10.1677/JOE-07-0309.
The year 1946 was not only the year that the Society for Endocrinology was founded, but also the year that Edward Kendall's compound E (cortisone) was first synthesised by Louis Sarett. By 1948, sufficient quantities of compound E were available for the rheumatologist Philip Hench to test it successfully for the first time in a patient with rheumatoid arthritis. It was immediately hailed as a 'wonder drug' and was shown to be effective in a number of inflammation-associated conditions, most notably rheumatoid arthritis. The subsequent development of endocrinology as a discipline is inextricably linked to the chemistry, biology and medicine of antiinflammatory glucocorticoids. Sixty years after the first chemical synthesis of cortisone, corticosteroids remain among the top ten most commonly used prescription and over the counter drugs. Basic and clinical studies of glucocorticoid biosynthesis, metabolism and action have trail-blazed developments in endocrinology ever since. This article surveys the extraordinary cortisone timeline, from first synthesis until now. The concluding scientific message is that intracrine metabolism of cortisone to cortisol via 11beta hydroxysteroid dehydrogenase type 1 likely sustains local amplification of glucocorticoid action at sites of inflammation throughout the body. The broader message is that the discovery of compound E by Kendall (basic scientist), its large-scale synthesis by Sarett (industrial chemist) and its therapeutic application by Hench (rheumatologist) serves as a paradigm for modern translational medicine. It is concluded that endocrinology will remain a force in health and disease if it continues to evolve sans frontières at the basic/applied/clinical science interface. A challenge for the Society for Endocrinology is to ensure this happens.
1946年不仅是内分泌学会成立的年份,也是路易斯·萨雷特首次合成爱德华·肯德尔的化合物E(可的松)的年份。到1948年,已有足够数量的化合物E可供风湿病学家菲利普·亨奇首次在一名类风湿关节炎患者身上成功进行测试。它立刻被誉为“神药”,并被证明在多种与炎症相关的病症中有效,最显著的是类风湿关节炎。内分泌学作为一门学科的后续发展与抗炎糖皮质激素的化学、生物学和医学有着千丝万缕的联系。可的松首次化学合成六十年后,皮质类固醇仍然是最常用的十大处方药和非处方药之一。从那时起,糖皮质激素生物合成、代谢和作用的基础与临床研究一直引领着内分泌学的发展。本文综述了从首次合成至今非凡的可的松历程。最后的科学结论是,可的松通过11β羟类固醇脱氢酶1型向皮质醇的细胞内代谢可能维持全身炎症部位糖皮质激素作用的局部放大。更广泛的结论是,肯德尔(基础科学家)发现化合物E、萨雷特(工业化学家)进行大规模合成以及亨奇(风湿病学家)将其用于治疗,为现代转化医学树立了典范。结论是,如果内分泌学继续在基础/应用/临床科学界面无国界地发展,它将在健康与疾病领域继续发挥重要作用。内分泌学会面临的一项挑战就是确保这种情况发生。