Discoveries hormones

At the time of the discovery of Met-enkephalin, its sequence was observed to be identical to that of residues 61—65 contained in the C-fragment of the pituitary hormone p-Hpotropin [12584-99-5] (p-LPH) (see Hormones), first isolated in 1964 (11). In 1976, the isolation of a larger peptide fragment, P-endorphin [60617-12-1] that also displayed opiate-like activity was reported (12). This peptide s 31-amino-acid sequence comprised residues 61—91 of P-LPH. Subsequentiy, another potent opioid peptide, dynorphin [72957-38-17, was isolated from pituitary (13). The first five amino acids (qv) of this 17-amino-acid peptide are identical to the Leu-enkephalin sequence (see Table 1). 

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. 

It grew out of another discovery in the senior author s laboratory, namely, that Reichstein s compound S could be converted in high yield into 11-epicortisol (1) by the enzymes of fungi of the genus Aspergillus The conversion of this inactive substance into the hormone cortisol thus became a problem of considerable importance. A route involving the 9,11-dehydro steroid (3) readily prepared from 11-epicortisol via its 21-acetate 11-tosylate... 

As with the other sex hormones, the first clinical use of Hiidrogens was for support therapy in individuals deficient in the endogenous hormone. The discovery that androgens exert an ana-hnlic effect greatly extended the indications for their use. 

In conclusion, the discovery of incretins has now come to an end in terms of therapeutic strategy of metabolic diseases since new medicines will be put on the market these coming years. However, a lot more needs to be done with regard to the physiological role of the hormones. Whereas the major filed of investigation for GLP-1 now relates to the effect of the peptide on the central nervous system and on (3-cell proliferation, for GIP it remains to understand its role in the numerous tissues where the corresponding receptor is expressed. 

A scientific procedure that turns the classical pharmacology approach upside down. Instead of finding the elusive receptor for a known hormone or transmitter what classical pharmacology aims at, reverse pharmacology is initiated through the discovery of the receptor gene and aspires to the identification of the receptors unknown ligand. 

Schapira M, Raaka BM, Samuels HH, Abagyan R. Rational discovery of novel nuclear hormone receptor antagonists. Proc Natl Acad Sci USA 2000 97 1008-13. 

R, Samuels HH. Discovery of diverse thyroid hormone receptor antagonists by high-throughput docking. Proc Natl Acad Sci USA 2003 100 7354-9. 

An important observation linking Ca + to hormone action involved the definition of the intracellular targets of Ca action. The discovery of a Ca -dependent regulator of phosphodiesterase activity provided the basis for a broad understanding of how Ca and cAMP interact within cells. 

Single protein kinases such as PKA, PKC, and Ca +-calmodulin (CaM)-kinases, which result in the phosphorylation of serine and threonine residues in target proteins, play a very important role in hormone action. The discovery that the EGF receptor contains an intrinsic tyrosine kinase activity that is activated by the binding of the hgand EGF was an important breakthrough. The insuhn and IGF-I receptors also contain intrinsic... 

Whole microbial cells as well as microbially derived enzymes have played a significant role in the production of novel antibiotics. The potential of microorganisms as chemical catalysts, however, was first fully realized in the synthesis of industrially important steroids. These reactions have assumed increasing importance following the discovery that certain steroids such as hydrocortisone have anti-inflammatory activity, whilst derivatives of the steroidal sex hormones are nsefiil as oral contraceptive agents. More recently, chiral inversion of non-steroidal anti-inflammatory dmgs (NS AIDs) has been demonstrated. 

Historically, the 1950s represented an important time in the control of human fertility. It was during that decade that the first combined oral contraceptives were developed. Shortly after the discovery that the exogenous administration of hormones such as progesterone successfully blocked ovulation, the use of hormonal steroids quickly became the most popular method of contraception worldwide. Specifically, combined oral contraceptives represent the most commonly used reversible form of contraception today and it is estimated that nearly 100 million women worldwide take oral contraceptives.1 Further, in the United States, it is estimated that at some time during their lives, more than 80% of women born since 1945 have used oral... 

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