Mode of action of chlorpromazine (CPZ) blockage on 13,14-dihydroprostaglandin F2-alpha formation in rat ovary

The mode of action of the inhibitory effect of CPZ on 13,14-dihydroprostaglandin F2-alpha (13, 14H₂-PGF2-alpha) formation in rat ovary was examined. The inhibition of 13, 14H₂-PGF2-alpha formation and of ovulation induced by a proestrus were completely recovered by an injection of hCG (25 IU/rat) or LH-RH (500 ng/rat) at 15:00 on the same day. 13,14H₂-PGF2-alpha formation and ovulation were not inhibited by a single injection of prolactin (PRL:6 IU/rat) at 13:00 on the day of proestrus. Repeated injection of PRL inhibited cyclic ovulation and 13,14H₂-PGF2-alpha formation. The estrus cycle of PRL treated animals showed a continuous state of diestrus. Although 13,14H₂-PGF2-alpha formation and ovulation were inhibited by the repeated injection of CPZ, the repeated-simultaneous injection of CPZ and bromocriptine at 10:00 once a day for 3 days from the first day of diestrus partly restored both and entirely reversed the suppression of the cyclic-changes in the in the vaginal smear pattern.

These results indicate that the inhibition of 13,14H₂-PGF2-alpha formation induced by a single injection of CPZ probably occurs via the suppression of LH-RH release from the hypothalamus, whereas PRL secretion may participate in the inhibitory effects of repeated injections of CPZ.