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  • Title: Subcellular effects of monohydroxytamoxifen in the rat uterus: steroid receptors and mitosis.
    Author: Dix CJ, Jordan VC.
    Journal: J Endocrinol; 1980 Jun; 85(3):393-404. PubMed ID: 7411007.
    Abstract:
    The administration of either monohydroxytamoxifen (25 micrograms) or oestradiol benzoate (25 micrograms) to immature rats resulted in similar depletion of the cytoplasmic oestrogen-receptor pool, with a transient (approx. 48 h) increase in nuclear oestrogen-receptor levels. Oestradiol benzoate increased uterine wet weight with a corresponding increase in uterine cytoplasmic progesterone-receptor levels, DNA content and cell division at 48 h. In contrast, monohydroxytamoxifen produced only a partial increase in uterine wet weight. Although the increase in concentration of uterine progesterone receptors (per mg DNA) by monohydroxytamoxifen was comparable to that produced by oestradiol benzoate, the nuclear antioestrogen-oestrogen-receptor complexes were unable to stimulate a large rise in whole uterine DNA content and cell division. Examination of stromal and epithelial mitotic activity 48 h after administration of 0.25, 2.5 and 25 micrograms oestradiol benzoate, monohydroxytamoxifen or tamoxifen showed that the inability of antioestrogens to stimulate oestrogen-like mitotic activity was not related to the dose of antioestrogen that was administered. It is suggested that the inability of the antioestrogen-oestrogen-receptor complexes to initiate the nuclear events which lead to cell division should be exploited in the investigation of the nuclear mechanism of oestrogen action. The high potency of monohydroxytamoxifen and its inherent biological activity, in that it is not metabolically activated before exerting its effects, provide clear advantages for its future use as a pharmacological probe.
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