Isoflavonoids and lignans, constituents of many plant foods, have been proposed as protective agents in those populations with a low incidence of hormone-dependent cancers. They may act by their inhibition of the metabolism of growth-promoting steroid hormones. This report describes the inhibition of 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase by six isoflavonoids and two lignans in human genital skin fibroblast monolayers and homogenates, and in benign prostatic hyperplasia tissue homogenates. In genital skin fibroblasts, genistein, biochanin A and equol were the most potent inhibitors of 5 alpha-reductase activity, each resulting in greater than 80% inhibition at a concentration of 100 microM. The IC50 values for genistein and a seven-compound mixture were approximately 35 microM and 20 microM (2.9 microM of each compound) respectively. Of the lignans, enterolactone was the most potent inhibitor. Inhibition by biochanin A was shown to be reversible. When genital skin fibroblast homogenates were used, biochanin A was found to inhibit 5 alpha-reductase isozymes 1 and 2 to differing extents (30% and 75% respectively). Genistein was shown to inhibit 5 alpha-reductase 2 in a non-competitive nature (Vmax and Km values without and with inhibitor were 30 and 20 pmol/mg protein per h and 177 and 170 nM respectively). All of the compounds tested inhibited 17 beta-hydroxysteroid dehydrogenase activity in genital skin fibroblast monolayers. When prostate tissue homogenates were used, the compounds tested were better inhibitors of 5 alpha-reductase 1 than 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Asian individuals have much lower incidences of prostate and breast cancer than populations from Western developed countries. They also consume a lower fat, higher fiber diet, with a large intake of phytoestrogens. These phytoestrogens may protect against hormone-dependent cancers and other diseases. Our study used established gas chromatography-mass spectrometry (GC-MS) methodologies to measure the concentrations of four phytoestrogens (daidzein, genistein, equol and enterolactone) in serum samples obtained from Japanese men (n = 102) and women (n = 125) > 40 y old. The results were compared with those obtained with samples from the UK. The Japanese men and women had higher (P < 0.001) concentrations of circulating daidzein, genistein and equol than individuals from the UK. The mean concentration of genistein in Japanese men, for example, was 492.7 nmol/L, compared with 33.2 nmol/L in men from the UK. The two populations, however, had similar serum concentrations of enterolactone. Furthermore, 58% of the Japanese men and 38% of the Japanese women had equol concentrations > 20 nmol/L, compared with none of the UK men and 2.2% of the UK women. These results support previously published GC-MS results from studies with low numbers of samples.
Plasma levels of the lignans enterodiol and enterolactone, and also the isoflavonic phyto-oestrogens daidzein, equol and genistein, are reported for postmenopausal Australian women consuming a traditional diet supplemented with linseed, soya flour or clover sprouts. Analysis was performed by gas chromatography-mass spectrometry, after enzymatic hydrolysis and ion-exchange chromatography. Following linseed supplementation, combined levels of enterolactone and enterodiol reached 500 ng/ml, whereas after soya flour or clover sprouts the respective concentrations of equol, daidzein and genistein reached 43, 312 and 148 ng/ml. Not all subjects were able to produce equol from daidzein. The possible relationship and role of these weak dietary oestrogens as restraining factors in the development of hormone-dependent cancers in Asian populations is discussed.
Management in the 1990s Sloan School of Management Massachusetts Institute of Technology---·I PP-EI II - Management in the 1990sManagement in the 1990s is an industry and governmental agency supported research program. Its aim is to develop a better understanding of the managerial issues of the 1990s and how to deal most effectively with them, particularly as these issues revolve around anticipated advances in Information Technology.Assisting the work of the Sloan School scholars with financial support and as working partners in research are: The conclusions or opinions expressed in this paper are those of the author(s) and do not necessarily reflect the opinion of the Massachussetts Institute of Technology, the Management in the 1990s Research Program, or its sponsoring organizations. IntroductionThis paper is deliberately narrowly focused. It does not deal with a large number of important issues in the fascinating and constantly evolving field of corporate strategy. It contributes, as do the other papers in this issue, to the mosaic which somehow defines the elusive concept of corporate strategy. As is so often true in emerging fields, no one has yet been able to define the concept and identify the elements in a way that is satisfactory to all people who consider themselves to be in the field. Nonetheless, the substantive work represented by all the articles in this issue attests to the constantly evolving nature of the field and each contributes to this evolution.The work discussed in this paper is a small piece of the strategic planning domain and deals not at all with the process of planning but rather with one piece of substantive content that organizations are using to create strategic moves that will help them deal successfully with the future. The work discussed here is part of a project that is ongoing in the Sloan School. It logically follows from Chandler's 5 classic study "Strategy and Structure" written at MIT in 1962. Chandler's book, which has been through eleven printings in the intervening years, is an example of the richness and complexity of the field of corporate strategy.-2-In this work, among other things, Chandler developed omne of the first notions of causality and balance in organizational processes and structure. He observed that in his sample of organizations the organization structure of the firm was changed to follow the strategy the firm was pursuing. For example, as executives at DuPont in 1919 decided on a strategy of aggressively extending their business out of munitions and into industrial chemicals they changed DuPont's organization structure and reporting relationships to reflect this strategic change.In a broadly analogous way, it is generally believed today that in successful firms, information technology should be managed to support business strategy and must fit the current organization structure.However, the main argument of this article is that this previously perceived one-way view is too limited. Beyond the use of information technology to support the existing busines...
A population-based case -control study of diet, inherited susceptibility and prostate cancer was undertaken in the lowlands and central belt of Scotland to investigate the effect of phyto-oestrogen intake and serum concentrations on prostate cancer risk. A total of 433 cases and 483 controls aged 50-74 years were asked to complete a validated FFQ and provide a non-fasting blood sample. Multivariate logistic regression analysis found significant inverse associations with increased serum concentrations of enterolactone (adjusted OR 0·40, 95 % CI 0·22, 0·71] and with the consumption of soy foods (adjusted OR 0·52, 95 % CI 0·30, 0·91). However, no significant associations were observed for isoflavone intake or serum genistein, daidzein and equol. This study supports the hypotheses that soy foods and enterolactone metabolised from dietary lignans protect against prostate cancer in older Scottish men.
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