Ovulating and LH-Releasing Activity of a Highly Potent Analog of Synthetic Gonadotropin-Releasing Hormone1

Abstract

The ovulating and gonadotropinreleasing activity of pGlu-His-Trp-Ser-Tyr-Gly- Leu-Arg-Pro-Gly-NH₂ (Gn-RH) and the highly potent analog [des-Gly-NH₂¹⁰, Pro-ethylamide⁹] Gn-RH (I) were compared in the pentobarbitalblocked proestrous rat. Serum LH and FSH were measured by radioimmunoassay and ovulation by the number of ova present in the fallopian tubes. Serum LH at 45 min after injection increased linearly as the dose level of Gn-RH and I increased. Invariably, the response was greater to a given dose of I, than to Gn-RH. Moreover, at the dose levels of Gn-RH, peak serum LH occurred between 15 and 30 min post-treatment, whereas maximal concentrations of LH in the serum occurred 45 min after the injection of I. The greater responses of the serum concentrations of FSH to I than to identical doses of Gn-RH also supports the greater activity of I, although ovulation occurred at dose levels of both Gn-RH and I which did not effect a serum increase. A dose level of 0.051 M£ I induced ovulation in all of the treated rats compared to 0.32 μg Gn-RH which effected a similar response. The percentage of rats ovulating was related to the dose level of both Gn-RH and I, but not the number of ova recovered from the oviducts. It is concluded from these data that a serum LH surge of 20–25 ng/ml induced by Gn-RH is sufficient to ovulate the pentobarbitalblocked proestrous rat. (Endocrinology93: 1449, 1973)