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  • Title: Increased potency of four analogues of LH-releasing hormone in man.
    Author: Kastin AJ, Arimura A, Gonzalez-Barcena D, Coy DH, Miller MC, Nishi N, Lee L, Duron-Huerta H, Schalch DS, Schally AV.
    Journal: Int J Fertil; 1974; 19(4):202-6. PubMed ID: 4376535.
    Abstract:
    Four analogues of LH-releasing hormone (LH-RH) were injected iv. in normal men at a dose of 25 mug: des-Gly-10NH2-LH-RH ethylamide (9-EA-LH-RH); des-Gly-10-NH2-LH-RH propylamide (9-PA-LH-PH), d-ala-6-LH-RH; and D-Ala-6, des Gly10-NH2-LH-RH ethylamide (D-Ala-6,9-EA-LH-RH). Each peptide tested was found to be more potent than LH-RH in releasing LH and, to a lesser extent, FSH. The times of the peak values of LH after the analogues were similar to LH-RH (about 20 minutes). However, LH as well as FSH levels were considerably delayed in returning to baseline after administration of D-Ala-6,9-EA-LH-RH. The half-time disappearances of the 9-EA and 9-PA analogues could be tested and were found to be similar to that of LH-RH. The increased potency and prolonged duration of action of D-Ala-6,9-EA-LH-RH suggest the potential usefulness of this compound in stimulating ovulation and perhaps spermatogenesis. Luteinizing hormone-releasing hormone (LH-RH), and 4 of its analogues were each tested in groups of 6 normal men. 25 mcg of des-Gly-10-NH2-LH-RH ethylamide (9-EA-LH-RH), des-Gly-10-NH2-LH-RH propylamide (9-PA-LH-RH), D-Ala-6-LH-RH, D-Ala-6, des Gly-10-nh2-lh-rh ethylamide (D-Ala-6,9-EA-LH-RH), and LH-RH were injected iv and the halftime disappearance from the blood of 2 of these analogues as well as LH and follicle stimulating hormone (FSH) levels were determined by radioimmunoassay. The peptides tested were found to be more potent than LH-RH in releasing LH and, to a lesser extent, FSH. The time of the peak values of LH and the analogues was about 20 minutes, however, LH and FSH were delayed in returning to baseline after D-Ala-6,9-EA-LH-RH. 9-EA and 9-PA analogues were similar to LH-RH in halftime disappearances. D-Ala-6,9EA-LH-RH showed increased potency and prolonged duration of action, thus suggesting potential usefulness in stimulating ovulation and perhaps spermatogenesis.
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