metribolone and Kidney-Neoplasms

Analyses of hormone receptors in cytosols from 41 renal cell carcinoma specimens were performed by the dextran-coated charcoal technique, using estradiol, synthetic progestin R5020 and synthetic androgen R1881. Binding data were calculated according to the method of Scatchard. Of 41 renal cell carcinomas estradiol receptor was detected in 11, R5020 receptor in 11 and R1881 receptor in 13. No significant correlation between histopathological findings and hormone receptors was observed. Patients were classified into those positive and negative for receptors. The clinical response of endocrine therapy for 17 with advanced residual or metastatic lesions after nephrectomy was studied in regard to the survival rates. Although there was no complete or partial regression in tumor size, the survival rate of patients with 1 or more receptors was significantly higher than that of patients negative for receptors (p less than 0.01). In conclusion, hormonal manipulation in patients with renal cell carcinoma cannot induce an antitumor effect but seems to increase survival in patients with receptors.

Topics: Adenocarcinoma; Aged; Estradiol; Estrenes; Female; Humans; Kidney Neoplasms; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Metribolone; Middle Aged; Promegestone; Receptors, Androgen; Receptors, Cell Surface; Receptors, Estrogen; Receptors, Progesterone; Testosterone

The purpose of this study was to partially characterize the steroid binding activity of murine renal tumor cells in continuous culture. The steroid receptor content of a cloned renal tumor cell line (RAG) and a subline RAG-2 was examined by sucrose gradient analysis, hydroxylapatite and dextran-coated charcoal methods. The RAG cells lacked estrogen- and progestin-binding activity, whereas specific 5 alpha-dihydrotestosterone (DHT) and dexamethasone (Dx) binding activities were detected as 8S peaks on low salt gradients. The specificity of DHT binding was examined by sucrose gradient analysis: DHT, R1881 and ORG2058 all completely inhibited [3H]DHT binding whereas diethylstilbestrol and Dx were ineffective. The androgen receptor content of the RAG cells was approx. 15 fmol/mg cytosol protein by the hydroxylapatite-filter assay, with an estimated Kd for methyltrienolone (R1881) of 5 nM at 0 degrees C. Scatchard analysis of [3H]Dx binding by RAG cytosol showed a Kd of 6 nM for Dx and 44 nM for corticosterone at 0 degrees C. Glucocorticoid receptor levels were estimated to be 182 fmol/mg cytosol protein by dextran-coated charcoal assay. Metabolism of [3H]testosterone and [3H]DHT by RAG cells was examined 1, 4 and 6 h after exposure to labeled hormone. Radioactive DHT was the primary intracellular metabolite recovered after exposure to [3H]testosterone. There was little conversion of DHT to androstanediol.

Topics: Animals; Binding Sites; Cell Line; Dexamethasone; Diethylstilbestrol; Dihydrotestosterone; Electrophoresis, Polyacrylamide Gel; Estradiol; Estrenes; Kidney Neoplasms; Metribolone; Mice; Pregnenediones; Steroids

The binding of methyltrienolone (R 1881, 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one), a highly active synthetic androgen, by cytosol preparations from human renal cell carcinoma was investigated. High-affinity, low-capacity binding components for R 1881 were detected in 3 out of 8 tumours analysed. The apparent dissociation constant of the R 1881-binder complexes was found to be in the range of 1.1-2.3 x 10(-9) mol/l. The number of binding sites in the positive tumours varied from 2.1 to 9.7 fmol/mg cytosol protein. Studies of binding specificity indicated a requirement for androgens. It is concluded that these binding components may be hormone receptors. If in consecutive studies this hypothesis holds true, progestins, most widely used in hormonal therapy of metastatic renal cancer, may possibly act on the tumour tissue by inhibiting the secretion of gonadotropins, thus lowering the blood levels of eventually growth-promoting.

Topics: Adenocarcinoma; Aged; Binding Sites; Cytosol; Estrenes; Female; Humans; In Vitro Techniques; Kidney Neoplasms; Male; Metribolone; Middle Aged; Testosterone Congeners