Large-scale prediction and testing of drug activity on side-effect targets. (1/3)

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Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor. (2/3)

Chlorotrianisene (TACE) exhibits in vitro little or no binding to the uterine estrogen receptor (ER) but demonstrates potent estrogenic activity in vivo, indicating that TACE is a proestrogen/proantiestrogen. Our earlier studies demonstrated that the incubation of TACE with rat liver microsomes and NADPH generates a reactive intermediate (T*) which binds covalently to proteins. The current study examined the possibility that T* may inactivate the uterine ER. The incubation of TACE with rat liver microsomes and NADPH in the presence of rat uteri, under conditions which generate T*, markedly decreased the binding capacity of the ER for [3H]estradiol (E2). The evidence indicates that ER inactivation was probably due to irreversible (covalent) binding of T* to the E2 binding site. The possibility that the antiestrogenic action of TACE and of other triphenylethylenes involves such a novel mechanism is discussed.  (+info)

Effect of oestrogen on liver function of prostatic cancer patients. (3/3)

Liver function of patients with cancer of the prostate gland was studied while they were receiving oestrogen therapy. When synthetic oestrogens were given, raised values of serum aspartate and alanine amino-transferase (S.G.O.T. and S.G.P.T.) were found in about 30-50% of them. As treatment continued the increased values usually returned to normal levels. No serious liver damage was observed, though the serum bilirubin content rose temporarily in some patients.  (+info)