Increased potency of four analogues of LH-releasing hormone in man.

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.