Effects of 4-hydroxy-4-androstene-3, 17-dione and 10-propargylestr-4-ene-3, 17-dione on the metabolism of androstenedione in human breast carcinoma and breast adipose tissues.
The effects of 4-hydroxy-4-androstene-3, 17-dione (4-OH-A) and 10-propargylestr-4-ene-3, 17-dione (PED) on the aromatization of androstenedione (A) and the conversion of A to testosterone (T) were studied in incubations with breast carcinoma and breast adipose tissues. Parallel studies were carried out to determine the effects of 4-OH-A and PED on A metabolism in tissue from 5 patients with breast carcinoma. At 11 micro M, both compounds fully inhibited aromatization, whereas the conversion of A to T was decreased in only 2 incubations. Studies with varying concentrations of 4-OH-A and PED demonstrated that both compounds inhibited estrone (E1) formation by 80% at a concentration of 0.085 micro M, with maximum effect at 0.34 micro M. 90% inhibition of estradiol (E2) formation was observed at inhibitor concentrations of 0.17 micro M or greater. T formation was slightly affected at 0.67 microM, but was progressively inhibited with increasing 4-OH-A or PED concentrations, reaching 70% at 11 micro M. Similar experiments with 4-OH-A in breast adipose tissue homogenates showed that a concentration of 0.1 micro M was sufficient to inhibit aromatization while T inhibition required 11 micro M. 4-OH-A and PED are selective inhibitors of aromatization in human breast tissues and may provide a mechanism for controlling estrogen responsive processes.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D010293:Pargyline / Q000031:analogs & derivatives*
D000735:Androstenedione; D010293:Pargyline; C033071:plomestane; C014594:formestane