Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells.
The authors studied the effects of 4-hydroxyandrostene-3,17-dione (4-OHA) on progesterone (P), 17 beta-estradiol (E2), and 20 alpha-hydroxy-4-pregnen-3-one synthesis and pregnenolone accumulation in cultured human midluteal cells. A dose-dependent inhibition with and without human chorionic gonadotropin (hCG) of E2 and P production was observed. The accumulation of pregnenolone was significantly enhanced three to fourfold by 4-OHA in this culture system, as compared with control value. In addition, a sevenfold increase on pregnenolone accumulation was observed in the presence of 4-OHA plus 10 IU of hCG as compared with control values and 2.2-fold as compared with the 4-OHA treatments. These in vitro findings indicate a direct effect of 4-OHA on luteal steroidogenesis. Nevertheless, the suppressive effect of 4-OHA on P and E2 production is located at different sites of the steroidogenic pathway. In addition, the results demonstrate that hCG in the presence of 4-OHA stimulated pregnenolone accumulation, suggesting that the inhibition of P synthesis is in some steps after the formation of pregnenolone. These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms.
Devoto
L
L
University of Chile, School of Medicine, Santiago.
Vega
M
M
Castro
O
O
Kohen
P
P
D004092:20-alpha-Dihydroprogesterone / Q000096:biosynthesis; D000328:Adult; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D047072:Aromatase Inhibitors; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D011284:Pregnenolone / Q000008:administration & dosage / Q000096:biosynthesis; D011374:Progesterone / Q000096:biosynthesis*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology
D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D004092:20-alpha-Dihydroprogesterone; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D011284:Pregnenolone; C014594:formestane