The effect of medroxyprogesterone acetate on aromatase and DNA polymerase alpha activities in breast tumours.
The effect of treatment with the progestogen medroxyprogesterone acetate (MPA) on the peripheral conversion of androstenedione to oestrone and tumour aromatase activity has been examined in post-menopausal women with advanced breast cancer. In addition to being a potent progestational compound, MPA also possesses glucocorticoid properties and glucocorticoids have been shown to stimulate in vitro aromatase activity. While some evidence was obtained of an increase in aromatase activity in tumour tissue after treatment with MPA, peripheral conversion of androstenedione to oestrone was similar when measured before (2.12 +/- 0.67%) and after (1.89 +/- 0.16%) treatment. DNA polymerase alpha activity, measured as a marker of cellular proliferation, decreased from 331 +/- 145 to 156 +/- 93 pmol thymidine triphosphate (TTP)/mg protein per h (P less than 0.02) in tumour samples examined before and after treatment. It is concluded that treatment with high doses of MPA has no effect on the peripheral conversion of androstenedione to oestrone but results in a significant reduction in tumour DNA polymerase alpha activity.
Purohit
A
A
Department of Chemical Pathology, St Mary's Hospital Medical School, Imperial College, University of London, England.
Lai
L C
LC
Singh
A
A
Coldham
N G
NG
Ghilchik
M W
MW
Reed
M J
MJ
James
V H
VH
D000368:Aged; D000735:Androstenedione / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004970:Estrone; D000735:Androstenedione; D017258:Medroxyprogesterone Acetate; D004257:DNA Polymerase II; D008525:Medroxyprogesterone