Inhibitory analogues of the luteinizing hormone-releasing hormone having D-aromatic residues in positions 2 and 6 and variation in position 3.
A single sc injection of 750 microgram/rat of [D-Phe2,Pro3,D-Phe6]-LH-RH on proestrus completely inhibited ovulation in 4-day cycling rats. Ovulation was inhibited partially at 375 microgram/rat. At the 720 microgram/rat dosage, analogues of LH-RH with D-Phe in positions 2 and 6, and with Sar, Arg, or Hyp in position 3, resulted in partial inhibitors and an inactive analogue with Thr substitution. In the same assay, analogues with D-Phe in position 2 and D-Trp in position 6 were partial inhibitors when D-Phe, Met, or Val were in position 3 and inactive with Ile substitution.
D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone