Investigations of droloxifene and other hormonal manipulations on N-nitrosomethylurea-induced rat mammary tumours. 2. Influence on oestrogen receptor
| Autor: | Hauff P, Staab Hj, Arnold W, Görlich M, Iduna Fichtner, Winterfeld G |
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| Rok vydání: | 1992 |
| Předmět: |
Drug
Cancer Research medicine.medical_specialty media_common.quotation_subject Ovariectomy Mammary gland Antineoplastic Agents Biology Internal medicine medicine Animals Binding site skin and connective tissue diseases Receptor media_common Estradiol Estrogen Antagonists Mammary Neoplasms Experimental Methylnitrosourea General Medicine Antiestrogen Aminoglutethimide Rats Tamoxifen medicine.anatomical_structure Endocrinology Oncology Receptors Estrogen Female hormones hormone substitutes and hormone antagonists medicine.drug Hormone |
| Zdroj: | Journal of cancer research and clinical oncology. 119(2) |
| ISSN: | 0171-5216 |
| Popis: | In N-nitrosomethylurea-induced rat mammary tumours, tamoxifen is found to compete at the binding sites of the oestradiol receptor if a receptor determination is performed 1 day following the last drug application to animals. Despite a higher binding affinity of droloxifene (3-OH-tamoxifen) to oestradiol receptor, compared to tamoxifen, its influence on the measurable receptor quantity is only very weak or not demonstrable. Therefore, binding affinity is not a valid explanation for the different influences of the two anti-oestrogens on the receptor. These only can be attributed to different behaviour patterns of both substances in relation to their half-lives and metabolism and accumulation in the organism. Owing to the short half-life of droloxifene, even 1 day after the last application too little drug is available to compete for oestradiol binding sites. In the case of both anti-oestrogenic substances, cessation of drug application for 8 weeks abolished any influence on the oestradiol receptor. Furthermore, failure of aminoglutethimide to influence the oestradiol receptor could be observed because this substance does not act via this receptor. The experiments performed confirm literature data regarding the effect of aminoglutethimide therapy on oestradiol receptors in breast tumour tissue of human beings. In summary: receptor investigations of N-nitrosomethylurea-induced rat mammary tumours, used as a model to test therapy regimens with droloxifene or other drugs with a short half-life, may be of limited value only. |
| Databáze: | OpenAIRE |
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