Comparison of the anti-LH/FSH-RH and anti-ovulatory activities of (D-Phe2, D-Leu6)-LH-RH and (D-Phe2, D-Ala6)-LH-RH.
The anti-LH/FSH-RH and antiovulatory activities of [D-Phe2, D-Leu6]-LH-RH and [D-Phe2, D-Ala6]-LH-RH were compared in rats. Both peptides inhibited the LH and FSH release induced by LH-RH in immature male rats, but, 4 hr after the injection, [D-Phe2, D-Leu6]-LH-RH still suppressed the LH and FSH release whereas the [D-Phe2, D-Ala6]-LH-RH did not. When the peptides were administered in equal doses on the afternoon of the day of proestrus in 4-day cycling rats, [D-Phe2, D-Leu6]-LH-RH more completely inhibited the ovulation occurring on the following morning than [D-Phe2, D-Ala6]-LH-RH. Thus, the incorporation of D-Leucine into position six of the decapeptide chain gives a more potent inhibitor than that resulting from the insertion of D-Alanine.
D000409:Alanine; D000818:Animals; D004971:Estrus / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007930:Leucine; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010060:Ovulation / Q000187:drug effects*; D010649:Phenylalanine; D010905:Pituitary Hormone Release Inhibiting Hormones / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D013329:Structure-Activity Relationship
D010905:Pituitary Hormone Release Inhibiting Hormones; D007987:Gonadotropin-Releasing Hormone; D010649:Phenylalanine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D007930:Leucine; D000409:Alanine