Discovery of Steroid Hormones

The beginnings of steroid chemistry go back to Adolf Windaus (1876-1959), who laid the foundations of this captivating field in 1905. Important contributions came from Adolf Butenandt (1903-1995) and Heinrich Otto Wieland (1877-1957). [15] Oestrone was the first sex hormone to he isolated from the urine ofpregnant women in 1929 hy Butenandt in Gottingen. [16] Later,heused 

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Pharmacological knowledge, gained with the discovery of steroid hormones, their nuclear receptors and their function in normal and malignant tissues, has been successfully translated into the first targeted drugs in oncology. 

Stumpf, W. E. Receptor localization of steroid hormones and drugs discoveries through the use of thaw-mount and dry-mount autoradiography. Braz. J. Med. Biol. Res. 1998, 37(2), 197-206. 

European Company to produce insulin and important suppliers of oestrone,274 Lederle,275 and Roussel Uclaf and Schering AG in Europe.276 Another development arising from this early research on steroids was Barton s pioneering studies in conformational analysis. The reminiscences include those by Fried on the discovery of the fluorosteroids at the Squibb Institute for Medical Research in New Jersey,277 and of studies of the biochemistry of steroid hormones linked to genetics and the history of cancer.278 Clearly, the problems of unravelling the complex mechanisms of steroid action have aroused considerable interest.279... 

As indicated earlier, plant products can be useful as starting materials for the semisynthetic preparation of other drugs. An important example in this regard is the Mexican yam, which produces a steroid precursor (diosgenin) vital to the synthesis of steroidal hormones used in oral contraceptives (i.e., progesterone). The availability of diosgenin eliminates numerous expensive steps in the organic synthesis of the basic steroid molecule. It was this discovery that contributed to the development of the pharmaceutical company Syntex (now a subsidiary of Hoffman LaRoche) and the development of the first birth control pill. 

The discovery of this stereoselective hydroxylation at C-11 and the introduction of diosgenin as a cheap raw material had dramatic effects in reducing the cost of steroid hormones. Thus in the early 1950 s, the price of progesterone dropped within just three years from 80 to 3/g. In its turn cortisone cost about 200/g in 1949 whereas today its cost is less than l/g. Several other steroids are also prepared by processes which include a microbiological oxidation step among them, cortexone and fluocortolone. 

Table V. Precursors of Steroid Hormones (Timetable of Discovery)...

Introduction - Valuable contributions continue to be made in unfolding the intimate mechanisms of sterol biosynthesis. While the steroid molecule continues to be a useful model for organic synthesis, structural modification of its nucleus has not yielded mammalian hormones with novel or markedly enhanced biological properties. The discovery of new hormones and biologically active substances in the plant and lower animal kingdom has sustained the chemist s interest in steroids. As the chemist adds to the understanding of the role of the steroid hormone in the life process, the biochemist quickens his search for the mechanism of its action. ... 

The discovery in 1954 that fluorination of the glucocorticoid hormone cortisol could bring about remarkable changes in the biological properties of the hormone was entirely unexpected and violated the then prevalent belief that synthetic variants could not surpass a naturally occurring hormone in its biological activity. Because of the impact that fluorination of steroids has had on subsequent developments in this area the history of the discovery of fluorocortisol will be briefly recounted. 

Cherkasov, A., Shi, Z., Fallahi, M., and Hammond, G.L. (2005) Successful in silico discovery of novel non-steroidal ligands for human sex hormone binding globulin. J. Med. Chem. 48, 3203-3213. 

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