Abstract

That the antiprogestin RU 486 delays or inhibits the LH surge, and induces premature luteolysis in monkeys and women concurrent with a reduction in LH/FSH secretion has been reported. Whether this inhibition of gonadotropin release was a result of action at the hypothalamic and/or pituitary level is unknown. Here, we utilized a rat pituitary cell culture system to evaluate direct RU 486 actions on pituitary gonadotropin secretion in vitro. Cell cultures were primed with 10 nM estradiol for 48 h in order to maintain progesterone receptors. Basal and GnRH-induced secretion were evaluated after a 4-hour incubation period. The progesterone antagoinist RU 486 inhibited GnRH-induced LH and FSH secretion in a dose-dependent manner, without affecting basal gonadotropin release. This inhibition of gonadotropin secretion was specific and antagonized by addition of progesterone in vitro.

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