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

Publisher Website
Google Scholar
Abstract
Peptide antagonists of LH-RH [leuteinizing hormone releasing hormone], [D-Phe2,D-Phe6]-LH-RH, [D-Phe2,D-Leu6]-LH-RH, [D-Phe2,D-Ala6]-LH-RH, [D-Phe2,Phe3,D-Phe6]-LH-RH, [DesHis2,D-Leu6]-LH-RH, and [DesHis2,D-Phe6]-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 [DesHis2,D-Phe6]-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-Phe2,Phe3,-D-PHe6]-LH-RH given in 4 divided doses at 30-min intervals starting 2 h before the LH-RH injection. LH levels had to be lower than 5 ng/ml (control: 20.9 ng/ml) to suppress ovulation. 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.