Potency and activity variation of LHRH analogs in different models and species.
The LHRH agonist [D-His(Bzl)6, Pro9-NHEt]LHRH was estimated to be 3.4, 4.4 and 9.2 times more potent than LHRH as a stimulator of ovulation in Nembutal-anesthetized, androgen-sterilized and diestrus rats, respectively; and 57 times more potent than LHRH as a stimulator of uterine growth in immature mice. Higher doses of agonist were required to induce ovulation in diestrus hamsters and mice than were needed in diestrus rats. Rats and hamsters also exhibited different sensitivities to an antagonist of LHRH. The LHRH antagonist [N-Ac delta 3-Pro1, D-pF-Phe2,D-Trp3,6]LHRH was active but higher doses were required to inhibit ovulation in hamsters than were needed in rats. In addition, treatment at 1500 hr on the day of proestrus in rats, in contrast to treatment at 1000 hr in hamsters, caused the greatest inhibition of ovulation. It is clear from these data, that the estimated in vivo potencies of analogs of LHRH are greatly influenced by species and animal model, as well as route of administration and biopharmaceutic factors previously reported.
D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004971:Estrus / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D010060:Ovulation / Q000187:drug effects; D010062:Ovulation Induction; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
D007987:Gonadotropin-Releasing Hormone; C036959:LHRH, Ac-dehydro-Pro(1)-4-F-Phe(2)-Trp(3,6)-; C029256:histrelin