cyproterone and Nasopharyngeal-Neoplasms

Since the publications of Martin, et al. (1948) and Schiff (1959), who were the first to report on the administration of sex hormones to juvenile nasopharyngeal fibroma (JNF) patients, several authors have described the different clinical effects and histologic changes after androgen and estrogen application. Since the mechanism of action of sex steroids in juvenile nasopharyngeal fibroma is almost unknown, the authors have studied androgen receptor binding in cultured tumor fibroblasts from three patients with JNF. Maximum androgen binding (Bmax) of the tumor fibroblasts approximated to that of genital skin fibroblasts, which served as a control androgen target tissue with high receptor density. Furthermore, in vitro experiments showed that the growth rate of tumor fibroblasts increased when testosterone was added to the culture medium, while the addition of two antiandrogens, cyproterone and flutamide, caused a reduction in growth rate. It is concluded from these results that JNF is a hormone-dependent tumor stimulated by testosterone whose growth rate may, at least in vitro, be reduced by antiandrogens such as cyproterone and flutamide.

Topics: Cell Division; Child; Cholestenone 5 alpha-Reductase; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Fibroblasts; Fibroma; Flutamide; Humans; Male; Nasopharyngeal Neoplasms; Oxidoreductases; Receptors, Androgen; Scrotum; Skin; Testosterone; Tritium; Tumor Cells, Cultured

Since Martin (1948) and Schiff (1959) first reported the use of sex hormones in JNF patients, many authors have described the various clinical effects and histological changes found after administration of androgens or estrogens. In 1980, Johns attempted unsuccessfully to detect estrogen receptors in the tissue of tumors from JNF patients. In 1987, however, Farag et al. succeeded in the demonstration of androgen receptors in homogenates of such tumor tissue.--In 1989, the authors were able to determine the uptake and receptor-binding of radioactively labelled dihydrotestosterone in cultured fibroblasts from a tumor from a 16-year-old JNF patient, and to confirm this result in two other cases. The maximum levels of hormone binding to the fibroblasts was much the same as is found with genital skin fibroblasts, included in the study as a control androgenic target-tissue with high receptor-density. At the same time it was demonstrated that it was possible to stimulate the tumor fibroblasts in vitro by adding testosterone to the culture medium. The attempt to block cell growth with the antiandrogen cyproterone acetate, was not successful, however. This can possibly be put down to the high progestogenic activity of this antiandrogen. Further in vitro studies with substances which are purely androgenic (e.g., flutamide) or with the acetate-free form of cyproterone (which has no progestogenic activity) will possibly be of help in the search for a substance capable of blocking tumor growth.

Topics: Adolescent; Cells, Cultured; Culture Media; Cyproterone; Cyproterone Acetate; Fibroblasts; Fibroma; Humans; Male; Nasopharyngeal Neoplasms; Receptors, Androgen; Skin; Testosterone; Tumor Cells, Cultured