Gonadotropin-releasing activity of two highly active and long-acting analogs of luteinizing hormone-releasing hormone after subcutaneous, intravaginal, and oral administration.

The gonadotropin-releasing activities of two synthetic analogs of luteinizing hormone-releasing hormone (LH-RH), D-Ala6-des-Gly10-LH-RH ethylamide and D-Leu6-des-Gly10-LH-RH ethylamide were evaluated in immature female rats after subcutaneous, intravaginal, and oral administration. Maximal peaks of serum LH and follicle-stimulating hormone (FSH) levels after administration of both analogs by any of the three routes were obtained at 2 hours. Therefore, serum gonadotropin levels declined slowly, so that at 6 hours LH levels had returned to base line values, whereas FSH levels remained elevated for up to 10 hours. The integrated serum gaondotropin levels after LH-RH and both analogs over a 10-hour period indicated that D-Leu6-des-Gly10-LH-RH EA and D-Ala6-des-Gly10-LH-RH EA released more LH and FSH than did the LH-RH decapeptide. The intense and long-acting properties of these analogs in releasing LH and FSH suggest the possibility that they may be more useful therapeutically than LH-RH.