Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jan 1990
The key scientific issue of the next century: the science of addiction.
The problem of addiction is believed to be the most important scientific issue of the next century. The solution to the riddle of pharmacologic, psychological, and social addiction to nicotine, heroin, alcohol, and a high-fat diet, and the discovery and implementation of strategies for spreading healthy "addictions" will aid in solving many major public health and social science problems in the next century. All-out efforts should be expended on the comprehensive development of a science of addiction and to the wide-scale effective application of the results of such research in order to promote health, prosperity, and peace for every community in the world.
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Ann. N. Y. Acad. Sci. · Jan 1990
Interactions between estrogens, androgens, progestins, and glucocorticoids in ZR-75-1 human breast cancer cells.
The human breast cancer cell line ZR-75-1 possesses androgen, estrogen, progesterone, and glucocorticoid receptors, thus offering a good model to study the specific role of each class of steroids in the control of breast cancer growth. Although the stimulatory action of classical estrogens (E2 and estrone) is well known, we have found a potent mitogenic effect of the adrenal estrogen androst-5-ene-3 beta,17 beta-diol (delta 5-diol) at concentrations within the range of those found in the serum of adult women, thus suggesting that delta 5-diol might be the most important estrogen in women. Androgens, on the other hand, exert a potent inhibitory effect on basal ZR-75-1 cell growth and completely reverse the stimulatory effect of estrogens on the same parameter. ⋯ Medroxyprogesterone acetate (MPA), a compound frequently used in the treatment of breast cancer in women, exerts its main inhibitory action through an androgen receptor-mediated action, whereas its glucocorticoid-like activity could play an additional role at high concentrations. All four classes of steroids are present, to various extents, as lipophilic esters of long-chain fatty acids. It is of interest to mention that all steroids that inhibit ZR-75-1 breast cancer cell growth (androgens, progestins, and glucocorticoids) stimulate the secretion and mRNA levels of gross cystic disease fluid protein-15 (GCDFP-15), whereas estrogens have the opposite effects, thus suggesting that GCDFP-15 could well be a good marker for monitoring the response to androgens, progestins, and antiestrogens during the course of breast cancer therapy.