TY - JOUR
T1 - 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
AU - Perel, E.
AU - Davis, S. P.
AU - Covey, D. F.
AU - Killinger, D. W.
N1 - Funding Information:
This work was supported by grants from The Medical Research Council of Canada, The National Cancer Institute of Canada and The National Institutes of Health - CA - 23582. Please send reprint requests to: Dr. D.W. Killinger, Medical Sciences Bldg., Rm. 7366, University of Toronto, Toronto, Canada M5S lA8.
PY - 1981/10
Y1 - 1981/10
N2 - 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 μM, 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 μM, with maximum effect at 0.34 μM. 90% inhibition of estradiol (E2) formation was observed at inhibitor concentrations of 0.17 μM or greater. T formation was slightly affected at 0.67 μM, but was progressively inhibited with increasing 4-OH-A or PED concentrations, reaching 70% at 11 μM. Similar experiments with 4-OH-A in breast adipose tissue homogenates showed that a concentration of 0.1 μM was sufficient to inhibit aromatization while T inhibition required 11 μM. 4-OH-A and PED are selective inhibitors of aromatization in human breast tissues and may provide a mechanism for controlling estrogen responsive processes.
AB - 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 μM, 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 μM, with maximum effect at 0.34 μM. 90% inhibition of estradiol (E2) formation was observed at inhibitor concentrations of 0.17 μM or greater. T formation was slightly affected at 0.67 μM, but was progressively inhibited with increasing 4-OH-A or PED concentrations, reaching 70% at 11 μM. Similar experiments with 4-OH-A in breast adipose tissue homogenates showed that a concentration of 0.1 μM was sufficient to inhibit aromatization while T inhibition required 11 μM. 4-OH-A and PED are selective inhibitors of aromatization in human breast tissues and may provide a mechanism for controlling estrogen responsive processes.
UR - http://www.scopus.com/inward/record.url?scp=0019776611&partnerID=8YFLogxK
U2 - 10.1016/0039-128X(81)90074-X
DO - 10.1016/0039-128X(81)90074-X
M3 - Article
C2 - 7314156
AN - SCOPUS:0019776611
SN - 0039-128X
VL - 38
SP - 397
EP - 405
JO - Steroids
JF - Steroids
IS - 4
ER -