Ovulation and Gonadotropin-Releasing Activity of [d-LEU6, DES-GLY NH210, PRO-ETHYLAMIDE9] -GNRH

Abstract

The ovulation-mducing and gonadotropin-releasing activities of [D-Leu⁶, des-Gly NH₂¹⁰, Pro-ethylamide⁹]-GnRH (II), were evaluated in rats, rabbits, and sheep. A sc dose of 3.4 ng/100 g body wt of the analog was equal to 160 ng/100 g body wt of GnRH in causing ovulation in the diestrous rat. At these dose levels, the integrated LH release was 1.9 times greater for the analog. Both the time of increase and maximum serum concentrations of LH were delayed after injection of the analog. Oral administration of II and GnRH to the proestrous rat resulted in an ED₅₀ for ovulation of 0.92 and 54 μg/ 100 g body wt, respectively. Serum levels of LH and FSH were highly variable for the various treatment groups when both releasing substances were administered orally. The intense ovulating activity of II was also evident in the estrous rabbit as indicated by an activity 31 times greater than that of GnRH. Additionally, the analog was at least 50 times more active than GnRH in releasing LH in both the mid-luteal and anestrous ewe. From our experiments with the cycling rat it appears that the intense ovulation-inducing activity of II can be accounted for by the intrinsic LH-releasing activity of the nonapeptide, rather than by a prolonged release stimulus.