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  • Title: Presence of proline in position 3 for potent inhibition of the activity of the luteinizing hormone releasing hormone and of ovulation.
    Author: Humphries J, Wan YP, Folkers K, Bowers CY.
    Journal: Biochem Biophys Res Commun; 1976 Oct 04; 72(3):939-44. PubMed ID: 791291.
    Abstract:
    The effect of various analogs of luteinizing hormone-releasing hormone (LH-RH) on the release of LH and follicle stimulating hormone (FSH) from isolated rat pituitaries was studied in vitro. (D-Phe (2), Pro (3), D-Trp (6))-LH-RH, in a ratio of analog to LH-RH of 50:1, completely inhibited the LH-RH-induced release of LH and FSH. Higher ratios of (D-Phe (2), Leu(3), D-Trp(6))-LH-RH and (D-Phe(2), Leu(3), D-PHe(6)-LH-RH to LH-RH also had a complete inhibitory effect, though they showed no agonistic activity. A single sc injection of the Pro(3)-analog (750 mcg) completely inhibited ovulation in rats, while a dose of 375 mcg inhibited ovulation by 50 percent. Complete inhibition of ovulation was also observed by the Leu(3)-analogs at 750 mcg with D-Phe(6), and at 1.5 mg with D-Trp(6). The in vitro and antiovulatory potency of LH-RH inhibitors was increased by the substitution of proline in position 3 of the inhibitory sequence.
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