INHIBITION OF INDUCTION OF 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN RAT CORPORA-LUTEA INVITRO BY THE PROGESTERONE ANTAGONIST RU486

To determine if the antiprogestagen RU486 has a direct effect on luteal progesterone secretion, whole corpora lulea or dispersed luteal cells were incubated in the presence of RU486. Whole corpora lutea, isolated from rats at day 5 of pseudopregnancy, were incubated individually in hormone-free medium. The concentrations of progesterone and 20-alpha-dihydro-progesterone in the medium plus corpus luteum was measured before and after 24 h of incubation. In the absence of RU486 the concentration of 20-alpha-dihydro-progesterone increased, while that of progesterone remained unchanged. In the presence of RU 6 (230-mu-M) the concentration of both progesterone and 20-alpha-dihydro-progesterone was increased. Dispersed luteal cells were incubated for 24 h in the presence of various amounts of RU486. In the absence and in the presence of 0.2 and 2.3-mu-M RU486 a high ratio between 20-alpha-dihydro-progesterone and progesterone was found, while in the presence of 23-mu-M RU486 the concentrations of progesterone and 20-alpha-dihydro-progesterone were equal. 20-alpha-Hydroxysteroid dehydrogenase (20-alpha-HSD) activity measured in luteal homogenates started to increase between 6 and 12 h of incubation. This increase could be prevented after incubation of the corpora lutea in the presence of 23 or 230-mu-M RU486 for 24 hrs. It is concluded that the progesterone antagonist RU486 can have a direct effect on luteal progesterone production. RU486 prevents the increase in 20-alpha-HSD activity that normally occurs during in vitro incubation. However, since these effects in vitro can only bc obtained with high concentrations of RU486, it is unlikely that this antiluteolytic effect plays a role after injection of RU486 in vivo.