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Conjugation of androgens and estrogens by human breast tumors in vitro
Abstract:
The metabolism of 3H-androstenedione (delta 4-A) and 3H-estriol (E3) was studied in 12 human breast tumors. Part of each tumor was analyzed for estrogen receptor content. Aliquots of tumor homogenates were incubated for 2 hr separately with 3H-delta 4-A and 3H-E3 in the presence of appropriate cofactors. No distinct differences emerged in the profiles of the unconjugated metabolites of 3H-delta 4-A, the major compounds in the approximate order of descendence being androsterone, androstanedione, testosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, epiandrosterone, and dihydrotestosterone. One tumor homogenate from an infiltrating lobular carcinoma converted 3H-delta 4-A to glucosiduronate metabolites (11%), of which androsterone, 6.4%; testosterone, 1.6%; and androstanediol, 0.6% predominated. The homogenate of this tumor and two other tumors converted 3H-E3 to 3H-E3-3S. Conversions of E3 to E3-3S in the other tumor homogenates were less than 0.6%. No correlation between receptor content and the capability of the tumor to conjugate delta 4-A or E3 evolved. However, correlations between steroid hormone metabolism and tumor histopathology may exist.