Suppression of LH RH induced ovulation in hamsters and rats by synthetic analogues of LH RH

Peptide antagonists of LH RH, [D Phe ²,D Phe ⁶] LH RH, [D Phe ²,D Leu ⁶] LH RH, [D Phe ²,D Ala ⁶] LH RH, [D Phe ²,Phe ³,D Phe ⁶] LH RH, [DesHis ²,D Leu ⁶] LH RH, and [DesHis ²,D Phe ⁶] LH RH, were examined for their ability to suppress LH RH induced ovulation in phenobarbital blocked hamsters and Nembutal blocked rats. All of these peptides, with the exception of [DesHis ²,D Phe ⁶] LH RH suppressed ovulation to various degrees, but also exhibited various degrees of agonistic activities. Complete suppression of ovulation was achieved in rats with 3 mg [D Phe ²,Phe ³, D Phe ⁶] LH RH given in 4 divided doses at 30 min intervals starting 2 hr before the LH RH injection. It was found that LH levels had to be lower than 5 ng/ml (control:20.9 ng/ml) to suppress ovulation. However, the extent of suppression of ovulation did not correlate with the serum LH levels < 5 ng/ml. The incidence of ovulation induced by the intrinsic LH RH activity of some of these analogues was similar to or greater than that resulting from administration of LH RH plus analogue, suggesting that the activity of LH RH itself was eliminated by pretreatment with the analogues.