Steroid modulation of aromatase activity in human cultured breast carcinoma cells.
Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10(-6) M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5 alpha-androstanedione (10(-6) M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10(-6) M) had no effect on aromatase activity while the progestational agent R5020 (10(-6) M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10(-6) M. Danazol (10(-6) M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10(-6) M) decreased E1 formation by more than 90% and aminoglutethimide (10(-6) M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue.
Perel
E
E
Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
Daniilescu
D
D
Kharlip
L
L
Blackstein
M
M
Killinger
D W
DW
D000735:Androstenedione / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000096:biosynthesis; D004970:Estrone / Q000096:biosynthesis; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D009277:Nandrolone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004970:Estrone; D000735:Androstenedione; D004958:Estradiol; D009277:Nandrolone; D001141:Aromatase; C002828:19-norandrostenedione; D006854:Hydrocortisone