Diamonds are forever: the cortisone legacy

Abstract

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 anti-inflammatory 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 11bhydroxysteroid 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.

11β-Hydroxysteroid Dehydrogenase Enzymes Modulate Effects of Glucocorticoids in Rheumatoid Arthritis Synovial Cells

“…In the late 1960s, a role for peripheral cortisone-cortisol interconversion in RA was described [2] and involvement of synovial tissue in this interconversion was shown [3]. However, more detailed elucidation of the underlying mechanisms was possible only after the necessary techniques became available [4]. …”

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

“…of cortisone from DCA ( 4 ), and this led to its commercial production on a small scale. Two years later, Hench, a rheumatologist at the Mayo Clinic, who worked closely with his colleague Kendall, an able steroid chemist, obtained a small supply of cortisone supplied by Merck ( 5 ). Hench showed that this compound caused a striking symptomatic improvement in patients with rheumatoid arthritis.…”

On gonads and gadflies: the estrus angle

“…Not least cortisone, which was crystallized independently by Edward Kendal (Mason et al 1936) and Tadeus Reichstein (Reichstein 1936) from bovine adrenal glands. Dubbed 'the hormone of life', the anti-inflammatory properties of cortisone made it one of the wonder drugs of the 20th century (Hillier 2007). Aldosterone, the salt-conserving adrenal steroid, would follow nearly two decades later (Simpson et al 1953), almost coincident with the discovery of ecdysone (see below).…”