metribolone and Uterine-Neoplasms

Primary endometrial carcinomas from 35 non-treated patients were investigated by measurement of androgen receptors in the tumor cytosols. Receptor analysis was done with a labelled synthetic androgen, methyltrienolone 3H-R1881 and triamcinolone acetonide, and dextran-coated charcoal absorption. The concentrations of androgen receptors in the endometrial carcinomas were, in decreasing order: highly-differentiated tumors, 15.7 +/- 1.8 (fmol/mg protein, mean +/- SE) (number of cases, 21); moderately differentiated tumors, 4.6 +/- 1.6 (n = 7); poorly differentiated tumors, undetectable in 7 out of 8 cases. Highly-differentiated tumors contained a much greater concentration of receptors than the two less differentiated ones. One highly-differentiated endometrial carcinoma with pyometra virtually lacked the receptor. The moderately differentiated endometrial carcinomas contained very low levels of the receptors. The poorly differentiated tumors virtually lacked the receptors. Metastatic lymph nodes from primary endometrial carcinomas with moderate differentiation had a very low receptor level. From these results, it is concluded that human endometrial carcinomas, particularly with histologically high differentiation, contain a considerable amount of androgen receptor and that the receptor concentrations appear to correlate with the histologic grade of tumor differentiation.

Topics: Adult; Aged; Carcinoma; Cytosol; Estrenes; Female; Humans; Metribolone; Middle Aged; Receptors, Androgen; Receptors, Steroid; Triamcinolone Acetonide; Uterine Neoplasms

This paper describes the dose-response inhibitory effects of a synthetic androgen, methyltrienolone, on the growth of a grade II endometrial adenocarcinoma in vitro. Derived from a nude mouse heterotransplant, this cell line has maintained the morphological characteristics of the original human tumor, remains tumorigenic in the nude mouse, forms colonies on soft agar, and exhibits low levels of estrogen receptors. Data reported in this paper indicate that the cells contain androgen binding sites. At low doses of 0.25 micrograms/ml methyltrienolone had no effect on these cells, whereas at 1.0 and 10.0 micrograms/ml there was significant dose dependent inhibition of cell growth and an increase in the cell doubling time. Both testosterone and dihydrotestosterone were not inhibitory to the cells except at high doses where inhibition was slight. Methyltrienolone was not inhibitory to normal human foreskin fibroblast cultures tested as a control for cytotoxicity of the synthetic androgen. These data suggest that androgens may play a role in the treatment of tumors not responsive to conventional forms of hormonal therapy.

Topics: Adenocarcinoma; Cell Division; Cell Line; Dihydrotestosterone; Dose-Response Relationship, Drug; Estradiol; Estrenes; Female; Humans; Metribolone; Testosterone; Testosterone Congeners; Uterine Neoplasms