Steroid research adrenal

Adrenal Cortical Hormones" under "Hormones" in ECT 1st ed., VoL 7, pp. 495—513, by H. B. MacPhUlamy, Ciba Pharmaceutical Products and T. F. Gallagher, Sloan-Kettering Institute for Cancer Research "Steroids with Cortical Hormone Activity" in ECT 1st SuppL, pp. 849—888, by G. Aimer and A. Wettstein, Ciba Limited, Basle "Adrenal-Cortical Hormones" under "Hormones" in ECT 2nd ed., Vol. 11, pp. 77—93, by W. R. Ebedein, The Children s Hospital of Philadelphia in ECT 3rd ed., Vol 12, pp. 575—602, by V. Petrow, Consultant. 

E.C. Kendall, Cortisone (New York, 1971) also see N. Rasmussen, Steroids in arms Hormones of the adrenal cortex and U S military research, 1940-45, submitted to Medical History. 

Although cholesterol is accepted as the major precursor of steroid hormones as a result of side-chain cleavage to pregnenolone (see below), research over the past decade or so has focused on the mechanisms by which steroidogenic tissues obtain cholesterol. It should be borne in mind that such tissues require cholesterol, not only for steroid synthesis but also for membrane synthesis, and hence require more of the precursor sterol than other tissues. Morris and Chaikoff [1] showed that the bulk of rat adrenal cholesterol was derived from circulating cholesterol, and later work revealed a similar state of affairs in humans. 

A great deal of research has been undertaken to determine if the dehydrogena-tion/isomerization reactions are properties of one system or of two separate enzymes (see Ref. 52) most of the evidence suggests that the former is true. Probably three, or even four, substrate-specific isomerases may occur in bovine adrenal cortex which can act on C19, C21 and C27 steroids. Likewise, separate 5-ene-3/3-HSDs may exist in the adrenal cortex for C19 and C21 steroids, because the latter did not compete with C19 steroids for active sites of the enzymes studied. 

In 1948 cortisone was made from bile acids in quantity sufficient for clinical trial, and the dramatic demonstration of its power to induce remission of rheumatoid arthritis was published the following year. In 1950 it was realised that cortisone was biologically inert and that the active natural hormone is hydrocortisone (cortisol). Since then an embarrassingly large number of synthetic steroids has been made and offered to the clinician. They are derived from natural substances (chiefly plant sterols), the constitutions of which approach most nearly to that of the steroids themselves. A principal aim in research is to produce steroids with more selective action than hydrocortisone, which induces a greater variety of effects than desired in any patient who is not suffering from adrenal insufficiency. 

Steroids include sex hormones and adrenal cortical hormones cortisone is one), cardiac glycosides, and bile acids. Because of their biological importance— and, undoubtedly, because of the fascinating complexity of the chemistry—the study of steroids has been, and is now, one of the most active areas of organic chemical research. 

The science of endocrinology was developing rapidly at this time. Outstanding was the isolation of insulin for treatment of diabetes by Banting in the early 1920s. Continuing research in this field led to the development of many hormones for treatment of a wide variety of disorders, especially the adrenal cortical steroid hormone (ACTH), cortisone, and thyroxine. 

DHEA (dehydroepiandrosterone) is another nonprescription antidepressant that has gone through cycles of popularity (Figure 6.2). DHEA, a steroid, is made from cholesterol in the adrenal gland and is part of the biochemical pathway in which hormones such as estrogen and testosterone are end-products. While its properties as a peripheral hormone are well characterized, less is known about DHEA s function in the brain. Media interest in DHEA arose when it was shown to prevent or slow memory loss in older populations. Further research showed that DHEA could influence neuronal function in the hippocampus, a region important for memory formation. However, several clinical studies showed mixed results when DHEA was used in... 

Data from many years of experimental animal research have tended to suggest that the steroids produced by the adrenal gland may also influence the growth and function of the prostate gland [19-22], and there is at present considerable interest in the role of the adrenal androgens in promoting the growth of human prostatic cancer [6, 23, 24]. These adrenal C,9-steroids,... 

Structure-Activity Relationship (SAR) Intensive and extensive clinical investigations have duly revealed that the anti-inflammatory activity emanated by the adrenal cortical steroids in humans invariably correlates intimately with their respective glucocorticoid activity. The advent of glaring and outstanding researches have evolved several synthetic steroids that exclusively possess distinctly higher glucocorticoid, and relatively lower mineralocorticosteroid activity in comparison to cortisone or cortisol that have been duly prepared, biologically screened, and marketed. 

Desoxycorticosterone was the first naturally occurring corticoid to be synthesized. It was prepared, before its isolation from the adrenal cortex, by Steiger and Reichstein (32). As a result of his synthesis of 11-desoxycorticosterone and other early work with corticoids, Reichstein later shared the Nobel Prize with Kendall, another chemist who was instrumental in carrying out early steroid syntheses, and with Hench, a rheumatologist who in 1929 discovered that cortisone is effective in the treatment of rheumatoid arthritis. Kendall s basic research ultimately led to the synthesis of cortisone from naturally occurring bile acids (33). 

In the study of the biogenesis and the transformation of steroids by the adrenal gland, the technique of paper chromatography applied to steroids by Zaffaroni and co-workers - has proved an invaluable aid to research, particularly where minute quantities of material were involved. Other ultramicro techniques for measuring adrenocortical hormones, such as the ultraviolet scanner and the automatic ultraviolet measuring fraction collector, have likewise been of considerable assistance. A variety of color reactions and similar analytical determinations have been widely employed in the study of the hormones and their metabolic transformation products. - ... 

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