The in vitro effect of substance P on the GnRH-induced LH release depends on the steroidal environment and is reverted by a NK1 receptor antagonist (RP 67580) in the cycling female rat

A previously study reported that administration of substance P on the morning of the proestrous day induces an inhibition of afternoon gonadotropin preovulatory surges in the female rat. It has also been shown, with a nonpeptide specific antagonist of the neurokinin 1 (NK1) receptor (RP 67580), that this effect is mediated by NK1 receptors. The present study used perifused anterior pituitaries from proestrous morning female rats and showed that the SP modulation of the GnRH-induced LH release is markedly dependent on the steroidal environment. In the absence of steroids or in the presence of 17 beta estradiol, or a combination of 17 beta estradiol and progesterone, SP inhibited the GnRH-induced LH release. In contrast, SP stimulated the GnRH-induced LH secretion in the presence of progesterone alone. However, the inhibitory or stimulatory effect of SP was antagonized by the specific NK1 receptor antagonist RP 67580.