Effects of RU486 on progesterone secretion by human preovulatory granulosa cells in culture.
The effects of RU486 on progesterone synthesis were studied in human preovulatory granulosa cells in culture. No effect was observed at 1 and 10 micrograms/mL, but at 100 micrograms/mL, RU486 inhibited the simulation of progesterone secretion induced by LH and cAMP. It is suggested that the main target of RU486 is the cytochrome P450scc function [catalyzing the formation of pregnenolone (D5P) from cholesterol], since no accumulation of D5P or hydroxy derivatives of progesterone was observed. As RU486 is an antiglucocorticosteroid and antiprogesterone agent, the effects of dexamethasone and progesterone were also investigated. Dexamethasone did not modify progesterone secretion, but progesterone inhibited its own synthesis in both the presence and absence of LH. Thus, under these experimental conditions RU486 displayed a progesterone-like effect. However, since the effect of RU486 was observed only at a concentration around 10(-4) M, the mechanism of action may not involve a receptor pathway and may not apply to most clinical circumstances.
Parinaud
J
J
Laboratoire de Fécondation In Vitro, INSERM U168, CHR La Grave, France.
Perret
B
B
Ribbes
H
H
Vieitez
G
G
Baulieu
E E
EE
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism; D015592:Immunoradiometric Assay; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology*; D011284:Pregnenolone / Q000096:biosynthesis; D011374:Progesterone / Q000378:metabolism*
D006908:Hydroxyprogesterones; D015735:Mifepristone; D011374:Progesterone; D011284:Pregnenolone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D000242:Cyclic AMP