Suppression of LH-RH-induced ovulation in hamsters and rats by synthetic analogues of LH-RH.
Peptide antagonists of LH-RH, [D-Phe2, D-Phe6]-LH-RH, [D-Phe2,D-Leu6]-LH-RH, [D-Phe2, D-Ala6]-LH-RH, [D-Phe2, D-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, Phe6]- LH-RH suppressed ovulation to various degrees, but alos 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 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 ovulationdid not correlate with the serum LH levels less than 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.
D000818:Animals; D006224:Cricetinae; D004971:Estrus; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D010060:Ovulation / Q000187:drug effects*; D010455:Peptides; D011247:Pregnancy; D051381:Rats; D013997:Time Factors
D010455:Peptides; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone