Physiologic Effects of a Gonadotropin Releasing Hormone Antagonist in Normal Women

Abstract

Because of their unique ability to cause pituitary desensitization [1], agonist analogs of GnRH have been used successfully to block gonadotropin output in the therapy of hormone sensitive tumors [2, 3] and other sex-steroid dependent diseases such as endometriosis [4] and uterine leiomyoma [5], as well as in precocious puberty [6], However, the complexity of action of these agonist analogs limits their use as physiologic probes. Additionally, the initial agonist phase prior to desensitization is not optimal for therapeutic uses in certain settings [2, 3]. Pure antagonists to the action of GnRH have now been developed which block the effect of GnRH on gonadotropin release in pituitary cell cultures [7], perifused pituitary cell columns [8] and intact animals [7, 9, 10]. These GnRH antagonists have been shown to compete with GnRH for receptor binding [11–15], but to stimulate receptor internalization at a slower rate than GnRH or its super-agonist analogs and to be processed differently [8, 16, 17].