Comparative Ovulation-Inducing Capacity of a Synthetic Luteinizing Hormone-Releasing Hormone and Two Analogs in Adult Rats and Mice

Abstract

Two analogs of luteinizing hormone-releasing hormone (LH-RH), H-Pyr-His-Trp-Ser-Tyr-[ d -Ala]-Leu-Arg-Pro-NH-CH 2 -CH 3 (AY-25,205) and H-Pyr-His-Trp-Ser-Tyr-[ d -Trp]-Leu-Arg-Pro-Gly-NH 2 (AY-25,650), were more potent than the synthetic LH-RH, H-Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 , in inducing ovulation in fluphenazine dihydrochloride-pretreated proestrous rats. The ED 50 values for AY-25,205, AY-25,650, and LH-RH were 3.0, 2.1, and 176.8 ng, respectively. AY-25,205 and AY-25,650 were also more effective in inducing ovulation in pregnant rats (ED 50 26.2 ng for AY-25,205 and 37.9 ng for AY-25,650) and pseudopregnant rats (ED 50 23.0 ng for AY-25,205 and 26.4 ng for AY-25,650) than was LH-RH (ED 50 values of 14.1 μg and 11.1 μg, respectively, for pregnant and pseudopregnant rats). Again, these two analogs were more efficient in advancing premature ovulation in diestrous rats (ED 50 10.8 ng for AY-25,205 and 14.1 ng for AY-25,650) than was LH-RH (ED 50 1.2 μg). At a dose of 80 ng/rat or higher, AY-25,205 and AY-25,650 were partially effective in inducing premature ovulation in metestrous rats, whereas LH-RH was ineffective even at a dose of 10 μg/rat. The ED 50 values for AY-25,205, AY-25,650, and LH-RH in inducing ovulation in diestrous mice were 4.6 ng, 3.5 ng, and 0.22 μg, respectively. These findings show that AY-25,205 and AY-25,650 have similar activity in inducing ovulation in rats and mice and are much more potent than LH-RH in causing maturation and rupture of growing follicles.